抗生素缓释的系列骨缺损修复材料的研究
|
摘要
骨与关节的感染给患者带来巨大的痛苦,对医患双方都带来巨大的负担。抗生素的应用对于绝大多数感染性疾病来说都有着很高的治愈率,然而骨与关节感染却例外。尽管目前外科技术和抗生素研究已经取得了长足的进步,但临床骨科的感染仍然是一个难题。治疗各种类型骨感染的主要目标是将感染区域细菌的负荷降低到一定水平,使骨愈合过程得以正常展开。骨骼肌肉损伤和外科植入物术后所致的感染通常的治疗方法是清创和引流以及全身使用抗生素。然而,全身抗生素治疗局部感染十分困难,因为只有很小一部分的药物可以到达目标部位发挥作用,特别是在局部血供不足时更是如此。反复的手术以及一味的延长抗生素使用时间常常是无效的,给个人和社会带来很大的负面影响,因此预防感染在骨科临床至关重要。局部抗生素载药系统可以递送高浓度的抗生素到病灶局部,同时避免长期大量静脉用药的潜在副作用,如果本身可降解并且还可促进骨修复,必将得到广泛应用。
目的：开发出一系列有机聚合物和无机的β-TCP为基础的有机无机复合材料,用不同的机制负载万古霉素,释放时间从数天到数周,用以满足临床上抗菌、抗感染各种时间跨度的需求。
材料和方法：应用天然来源的聚合物,海藻酸钠、壳聚糖等在比较温和的条件下溶解,并且和p-磷酸三钙和万古霉素相混合,首先用滴入法加冷冻干燥的方法制备出海藻酸钙/β-TCP/万古霉素复合颗粒状材料,并对其进行聚己内酯的涂层处理,记录其SEM.TGA等表征,观测材料在涂层前后的抗生素体外释放特征；随后应用混合加冷冻干燥的方法制备壳聚糖/β-TCP/万古霉素复合多孔材料,也对其进行聚己内酯涂层处理,对其涂层前后的表征和释药特性进行检测；最后以再生丝素蛋白为原料,应用醇／水制孔法,冷冻干燥法制备出多孔的中空管状材料,在中空管道中填加β-TCP/万古霉素,通过对其体外释药特性和体内生物相容性以及骨缺损修复的效果的评估。
结果：本课题研究的5种抗生素缓释系统在体外均表现出良好的理化性能,表现出不同时间跨度的抗生素缓释能力,海藻酸钙/β-TCP/万古霉素微球可以在体外缓释3天,随后完全崩解；PCL涂层可以一定程度控制海藻酸钙/β-TCP/万古霉素微球在体外PBS中的扩散释放；浓度为2.5w/v%的PCL在海藻酸钙/β-TCP/万古霉素微球表面涂布最均匀,有效体外缓释时间能够从涂层前的3天延长到涂层后的8天。PCL涂层的海藻酸钙/β-TCP/万古霉素微球由于生物相容性好,缓释抗生素,可作为预防骨科相关感染的良好候选材料。壳聚糖/β-TCP/万古霉素可以在一定条件下,利用冷冻干燥的方法,制备出TCP分布均匀的,多孔的材料,材料的孔径可在196.4μm~205.2μm之间,孔隙率达到92.0%～95.5%之间。壳聚糖/β-TCP在一定条件下可以通过冷冻温度的调节来调节孔径的大小。壳聚糖/β-TCP/万古霉素复合抗生素缓释材料可在体外保证14d左右的万古霉素释放,并且仍然具有抗菌活性。在壳聚糖/TCP/万古霉素复合抗生素缓释系统的表面涂层聚己内酯(PCL)可以有效延缓该系统的早期爆释,药物仅通过聚合物涂层表面由于溶剂挥发所形成的小孔渗透水分和药物,因此,控制了药物的释放,使材料的释放期限,从涂层前的12天,延长到涂层后的最长42天；2.5%PCL的二氯甲烷溶液,涂层效果最佳,且能够达到最佳的万古霉素缓释效果,2.5%的PCL涂层的材料在整个缓释观测期内没有明显的爆释,第1d的释药率仅为7.12±2.3%；第12的累积释放率仅为40.58±2.1%。再生丝素蛋白中空管状多孔支架内填充β-TCP和抗生素,组织相容性良好,用来修复大段的兔骨缺损,不结合种子细胞,也能取得良好的修复效果；这种新型多孔丝蛋白胶囊包裹万古霉素及β-TCP复合材料,可在体外保持5天的药物释放,在体内试验中表现出了明显的预防感染作用。
结论：本课题所研究的几种聚合物/无机物复合抗生素缓释材料,一系列的体外缓释物检测表明,这些缓释材料的药物释放期限跨度从2-3天到6周,经过进一步的优化和改良后,必然有望可以满足从预防骨和关节感染到治疗慢性骨髓炎这一临床上至今棘手的难题。
Bone and joint infections are painful for patients and frustrating for both them and their doctors. The high success rates of antimicrobial therapy in most infectious diseases have not yet been achieved in bone and joint infections owing to the physiological and anatomical characteristics of bone. Despite the great improvement in research of the surgical techniques and antibiotics, the orthopaedic infection is still a big puzzle. The main goal of the treatment of kinds of bone infection is to lower the level of bacteria in the infectious area, so that the bone healing can happen. Debridement, irrigation and use antibiotcs systematicly are the common way to treat the bone and joint infection, while systematic antibiotics is very difficult to be taken into the local infection site, there will be only a very small part of them can get to the target, especially for those who have ischemic problems after big debridement. Repeatedly operation and enlength the usage of antibiotics are of no use at that time. Thus it is a critical thing to prevent the infection in the orthopaedic clinics. It must be very popular, if there is a antibiotics delivery system that can be degradable and can deliver high concentrations of antibiotics to local site and can help bone healing as well.
Objectives:To design and fabricate a series of inorganic/organic composites that can load on vancomycin with different delivery mechanism. The effective delivery lasts from several days to several weeks so that they can meet with the need of different length of antibiotic treatment to different infection conditions.
Materials and Methods:Sodium alginate(SA) and chitosans(CS) were dissolved and blended with vancomycin and TCP. Put SA dropwise into calcium ion solution to form small spheres of calcium algiante/TCP/vancomycin and thus freeze dried those spheres, then we got the spherens of calcium alginate/TCP/vancomycin. Then polycaprolactone (PCL) solutions were used to coat these spheres ang characteristics such as SEM and TGA were assessed as well as their drug delivery. And CS/TCP/vancomycin porous scaffold were made with freeze drying. The characteristics such as SEM,TGA and their drug delivery were also observed. Then we coate these porous scaffold with PCL again and those characteristics and drug delivery characteritcs were assesed again. In the end, silk fibroin (SF) was poured into the mould and lyophilized to be a tube like porous capsule. TCP and vancomycin were packed into this kind of capsule to be a simple delivery system, the drug delivery of which was tested in vitro and the bone induction of which was tested in vivo.
Result:There were5materials tested in this thesis. AG/TCP/vancomycin could deliver vancomycin effectively for3days in vitro, and could be increased to5days(1.25%PCL) and8days(2.5%PCL); CS/TCP/vancomycin composites with the pore of196.4μm～205.2μm, could deliver vancomycin effectively for12days, and could be increase to maximum42days after coated with2.5%PCL solutions. As to the SF capsule packed with TCP and vancomycin could help heal the radius bone defect well and can effectively prevent the infection postoperatively. This kind of capsule can deliver antibiotics for5days in vitro.
Conclusions:The several polymer/inorganic composites loaded with antibiotics were developed and tested, and the conclusions were that these delivery systems can deliver antibiotics for several days (3d) to several weeks (6w). It must be vey popular and can fit the need of the clinics from the prophylaxis of bone and joint infection to the treatment of chronic osteomyelitis if some procedures can be improved.
目的：开发出一系列有机聚合物和无机的β-TCP为基础的有机无机复合材料,用不同的机制负载万古霉素,释放时间从数天到数周,用以满足临床上抗菌、抗感染各种时间跨度的需求。
材料和方法：应用天然来源的聚合物,海藻酸钠、壳聚糖等在比较温和的条件下溶解,并且和p-磷酸三钙和万古霉素相混合,首先用滴入法加冷冻干燥的方法制备出海藻酸钙/β-TCP/万古霉素复合颗粒状材料,并对其进行聚己内酯的涂层处理,记录其SEM.TGA等表征,观测材料在涂层前后的抗生素体外释放特征；随后应用混合加冷冻干燥的方法制备壳聚糖/β-TCP/万古霉素复合多孔材料,也对其进行聚己内酯涂层处理,对其涂层前后的表征和释药特性进行检测；最后以再生丝素蛋白为原料,应用醇／水制孔法,冷冻干燥法制备出多孔的中空管状材料,在中空管道中填加β-TCP/万古霉素,通过对其体外释药特性和体内生物相容性以及骨缺损修复的效果的评估。
结果：本课题研究的5种抗生素缓释系统在体外均表现出良好的理化性能,表现出不同时间跨度的抗生素缓释能力,海藻酸钙/β-TCP/万古霉素微球可以在体外缓释3天,随后完全崩解；PCL涂层可以一定程度控制海藻酸钙/β-TCP/万古霉素微球在体外PBS中的扩散释放；浓度为2.5w/v%的PCL在海藻酸钙/β-TCP/万古霉素微球表面涂布最均匀,有效体外缓释时间能够从涂层前的3天延长到涂层后的8天。PCL涂层的海藻酸钙/β-TCP/万古霉素微球由于生物相容性好,缓释抗生素,可作为预防骨科相关感染的良好候选材料。壳聚糖/β-TCP/万古霉素可以在一定条件下,利用冷冻干燥的方法,制备出TCP分布均匀的,多孔的材料,材料的孔径可在196.4μm~205.2μm之间,孔隙率达到92.0%～95.5%之间。壳聚糖/β-TCP在一定条件下可以通过冷冻温度的调节来调节孔径的大小。壳聚糖/β-TCP/万古霉素复合抗生素缓释材料可在体外保证14d左右的万古霉素释放,并且仍然具有抗菌活性。在壳聚糖/TCP/万古霉素复合抗生素缓释系统的表面涂层聚己内酯(PCL)可以有效延缓该系统的早期爆释,药物仅通过聚合物涂层表面由于溶剂挥发所形成的小孔渗透水分和药物,因此,控制了药物的释放,使材料的释放期限,从涂层前的12天,延长到涂层后的最长42天；2.5%PCL的二氯甲烷溶液,涂层效果最佳,且能够达到最佳的万古霉素缓释效果,2.5%的PCL涂层的材料在整个缓释观测期内没有明显的爆释,第1d的释药率仅为7.12±2.3%；第12的累积释放率仅为40.58±2.1%。再生丝素蛋白中空管状多孔支架内填充β-TCP和抗生素,组织相容性良好,用来修复大段的兔骨缺损,不结合种子细胞,也能取得良好的修复效果；这种新型多孔丝蛋白胶囊包裹万古霉素及β-TCP复合材料,可在体外保持5天的药物释放,在体内试验中表现出了明显的预防感染作用。
结论：本课题所研究的几种聚合物/无机物复合抗生素缓释材料,一系列的体外缓释物检测表明,这些缓释材料的药物释放期限跨度从2-3天到6周,经过进一步的优化和改良后,必然有望可以满足从预防骨和关节感染到治疗慢性骨髓炎这一临床上至今棘手的难题。
Bone and joint infections are painful for patients and frustrating for both them and their doctors. The high success rates of antimicrobial therapy in most infectious diseases have not yet been achieved in bone and joint infections owing to the physiological and anatomical characteristics of bone. Despite the great improvement in research of the surgical techniques and antibiotics, the orthopaedic infection is still a big puzzle. The main goal of the treatment of kinds of bone infection is to lower the level of bacteria in the infectious area, so that the bone healing can happen. Debridement, irrigation and use antibiotcs systematicly are the common way to treat the bone and joint infection, while systematic antibiotics is very difficult to be taken into the local infection site, there will be only a very small part of them can get to the target, especially for those who have ischemic problems after big debridement. Repeatedly operation and enlength the usage of antibiotics are of no use at that time. Thus it is a critical thing to prevent the infection in the orthopaedic clinics. It must be very popular, if there is a antibiotics delivery system that can be degradable and can deliver high concentrations of antibiotics to local site and can help bone healing as well.
Objectives:To design and fabricate a series of inorganic/organic composites that can load on vancomycin with different delivery mechanism. The effective delivery lasts from several days to several weeks so that they can meet with the need of different length of antibiotic treatment to different infection conditions.
Materials and Methods:Sodium alginate(SA) and chitosans(CS) were dissolved and blended with vancomycin and TCP. Put SA dropwise into calcium ion solution to form small spheres of calcium algiante/TCP/vancomycin and thus freeze dried those spheres, then we got the spherens of calcium alginate/TCP/vancomycin. Then polycaprolactone (PCL) solutions were used to coat these spheres ang characteristics such as SEM and TGA were assessed as well as their drug delivery. And CS/TCP/vancomycin porous scaffold were made with freeze drying. The characteristics such as SEM,TGA and their drug delivery were also observed. Then we coate these porous scaffold with PCL again and those characteristics and drug delivery characteritcs were assesed again. In the end, silk fibroin (SF) was poured into the mould and lyophilized to be a tube like porous capsule. TCP and vancomycin were packed into this kind of capsule to be a simple delivery system, the drug delivery of which was tested in vitro and the bone induction of which was tested in vivo.
Result:There were5materials tested in this thesis. AG/TCP/vancomycin could deliver vancomycin effectively for3days in vitro, and could be increased to5days(1.25%PCL) and8days(2.5%PCL); CS/TCP/vancomycin composites with the pore of196.4μm～205.2μm, could deliver vancomycin effectively for12days, and could be increase to maximum42days after coated with2.5%PCL solutions. As to the SF capsule packed with TCP and vancomycin could help heal the radius bone defect well and can effectively prevent the infection postoperatively. This kind of capsule can deliver antibiotics for5days in vitro.
Conclusions:The several polymer/inorganic composites loaded with antibiotics were developed and tested, and the conclusions were that these delivery systems can deliver antibiotics for several days (3d) to several weeks (6w). It must be vey popular and can fit the need of the clinics from the prophylaxis of bone and joint infection to the treatment of chronic osteomyelitis if some procedures can be improved.
引文
1. Lew, P.D.P. and P.F.A. Waldvogel, Osteomyelitis. The Lancet,2004.364(9431):p. 369-379.
2. Zimmerli, W., A. Trampuz, and P.E. Ochsner, Current concepts:Prosthetic-joint infections. New England Journal of Medicine,2004.351(16):p.1645-1654.
3. Widmer, A.F., New developments in diagnosis and treatment of infection in orthopedic implants. Clinical Infectious Diseases,2001.33:p. S94-S106.
4. Kilgus, D.J., D.J. Howe, and A. Strang, Results of periprosthetic hip and knee infections caused by resistant bacteria. Clinical Orthopaedics and Related Research, 2002(404):p.116-124.
5. Proctor, R.A., et al., Small colony variants:a pathogenic form of bacteria that facilitates persistent and recurrent infections. Nature Reviews Microbiology,2006. 4(4):p.295-305.
6. Betsch, B.Y., et al., Treatment of joint prosthesis infection in accordance with current recommendations improves outcome. Clinical Infectious Diseases,2008.46(8): p.1221-1226.
7. Salgado, C.D., et al., Higher risk of failure of methicillin-resistant Staphylococcus aureus prosthetic joint infections. Clinical Orthopaedics and Related Research, 2007(461):p.48-53.
8. Soriano, A., et al., Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia. Clinical Infectious Diseases,2008.46(2):p.193-200.
9. Radin, S., et al., Calcium phosphate ceramic coatings as carriers of vancomycin. Biomaterials,1997.18(11):p.777-782.
10. Feng, K., et al., Novel antibacterial nanofibrous PLLA scaffolds. Journal of Controlled Release,2010.146(3):p.363-369.
11. Ozkan, S., D.M. Kalyon, and X.J. Yu, Functionally graded beta-TCP/PCL nanocomposite scaffolds:In vitro evaluation with human fetal osteoblast cells for bone tissue engineering. Journal of Biomedical Materials Research Part A,2010. 92A(3):p.1007-1018.
12. Waldvoge.Fa, G. Medoff, and M.N. Swartz, Osteomyelitis:a review of clinical features, therapeutic considerations and unusual aspects. New England Journal of Medicine,1970.282(4):p.198-206.
13. Cierny, G., J.T. Mader, and J.J. Penninck, A clinical staging system for adult osteomyelitis. Clinical Orthopaedics and Related Research,2003(414):p.7-24.
14. Chang, W., et al., Adult osteomyelitis:Debridement versus debridement plus Osteoset T (R)pellets. Acta Orthopaedica Belgica,2007.73(2):p.238-243.
15. Dacquet, V., et al., Antibiotic-impregnated plaster of Paris beads-Trials with teicoplanin. Clinical Orthopaedics and Related Research,1992(282):p.241-249.
16. Javed, S. and K. Kohli, Local Delivery of Minocycline Hydrochloride:A Therapeutic Paradigm in Periodontal Diseases. Current Drug Delivery,2010.7(5):p. 398-406.
17. Sia, I.G. and E.F. Berbari, Osteomyelitis. Best Practice & Research in Clinical Rheumatology,2006.20(6):p.1065-1081.
18. Mader, J.T., et al., Antimicrobial treatment of chronic osteomyelitis. Clinical Orthopaedics and Related Research,1999(360):p.47-65.
19. De, P., et al., Structure-release rate correlation in collagen gels containing fluorescent drug analogs. Biomaterials,2005.26:p.7164-72.
20. Langer, R., Invited review:polymeric delivery systems for controlled drug release. Chemical Engineering Comminication,1980.6.
21. Nikkola, L., P. Viitanen, and N. Ashammakhi, Temporal Control of Drug Release From Biodegradable Polymer:Multicomponent Diclofenac Sodium Releasing PLGA 80/20 Rod. Journal of Biomedical Materials Research Part B-Applied Biomaterials, 2009.89B(2):p.518-526.
22. Buchholz, H.W. and Engelbre.H, Deposit effect of some antibiotics in mixing with artificial resin palacos. Chirurg,1970.41(11):p.511-&.
23. Anguita-Alonso, P., et al., Comparative study of antimicrobial release kinetics from polymethylmethacrylate. Clin Orthop Relat Res,2006.445:p.239-44.
24. Hartley, M.P. and S. Sanderson, Use of antibiotic impregnated polymethylmethacrylate beads for the treatment of chronic mandibular osteomyelitis in a Bennett's wallaby (Macropus rufogriseus rufogriseus). Australian Veterinary Journal,2003.81(12):p.742-744.
25. Scott, D.M., J.C. Rotschafer, and F. Behrens, Use of vancomycin and tobramycin polymethymethacrylate impregnated beads in the management of chronic osteomyelitis Drug Intelligence & Clinical Pharmacy,1988.22(6):p.480-483.
26. Evans, R.P., Successful treatment of total hip and knee infection with articulating antibiotic components-A modified treatment method. Clinical Orthopaedics and Related Research,2004(427):p.37-46.
27. Walenkamp, G., Self-mixed antibiotic bone cement:western countries learn from developing countries. Acta Orthopaedica,2009.80(5):p.505-507.
28. Rasyid, H.N., et al., Concepts for increasing gentamicin release from handmade bone cement beads. Acta Orthopaedica,2009.80(5):p.508-513.
29. Thielen, T., et al., Mechanical behaviour of standardized, endoskeleton-including hip spacers implanted into composite femurs. International Journal of Medical Sciences,2009.6(5):p.280-286.
30. Diez-Pena, E., et al., Gentamicin sulphate release from a modified commercial acrylic surgical radiopaque bone cement. Ⅰ. Influence of the gentamicin concentration on the release process mechanism. Chemical & Pharmaceutical Bulletin,2002.50(9): p.1201-1208.
31. Belt, v.d.H., et al., Surface roughness, porosity and wettability of gentamicin-loaded bone cements and their antibiotic release. Biomaterials,2000.21: p.1981-7.
32. Neut, D., et al., The effect of mixing on gentamicin release from polymethylmethacrylate bone cements. Acta Orthopaedica Scandinavica,2003.74(6): p.670-676.
33. Peltier, L.F., The use of Plaster of Paris to fill defects in bone. Clinical Orthopaedics,1961 ((21):p.1-31.
34. Mackey, D., A. Varlet, and D. Debeaumont, Antibiotic loaded plaster of Paris pellets:an in vitro study of a possible method of local antibiotic therapy in bone infection. Clinical Orthopaedics,1982((167):p.263-8.
35. El-Ghannam, A., K. Jahed, and M. Govindaswami, Resorbable bioactive ceramic for treatment of bone infection. Journal of Biomedical Materials Research Part A, 2010.94A(1):p.308-316.
36. Scharer, B.M. and S.M. Sanicola, The In Vitro Elution Characteristics of Vancomycin From Calcium Phosphate-Calcium Sulfate Beads. Journal of Foot & Ankle Surgery,2009.48(5):p.540-542.
37. Gautier, H., et al., In vitro characterisation of calcium phosphate biomaterials loaded with lidocaine hydrochloride and morphine hydrochloride. Journal of Materials Science-Materials in Medicine,2010.21(12):p.3141-3150.
38. Sanicola, S.M. and S.F. Albert, The in vitro elution characteristics of vancomycin and tobramycin from calcium sulfate beads. The Journal of Foot and Ankle Surgery. 44(2):p.121-124.
39. Krasko, M.Y., et al., Gentamicin extended release from an injectable polymeric implant. Journal of Controlled Release,2007.117(1):p.90-96.
40. Schnieders, J., et al., Controlled release of gentamicin from calcium phosphate poly(lactic acid-co-glycolic acid) composite bone cement. Biomaterials,2006.27(23): p.4239-4249.
41. Hendricks, K.J., et al., Elution characteristics of tobramycin from polycaprolactone in a rabbit model. Clinical Orthopaedics and Related Research, 2001(392):p.418-426.
42. Foster, L.J.R., et al., Chitosan-Vancomysin Composite Biomaterial as a Laser Activated Surgical Adhesive with Regional Antimicrobial Activity. Biomacromolecules, 2010.11(12):p.3563-3570.
43. Sarasam, A., et al., Antibacterial activity of chitosan-based matrices on oral pathogens. Journal of Materials Science:Materials in Medicine,2008.19(3):p. 1083-1090.
44. Bleier, B.S., et al., Antibiotic eluting chitosan glycerophosphate implant in the setting of acute bacterial sinusitis:A rabbit model. American Journal of Rhinology & Allergy,2010.24(2):p.129-132.
45. Draget, K.I., G. SkjakBraek, and O. Smidsrod, Alginate based new materials. International Journal of Biological Macromolecules,1997.21(1-2):p.47-55.
46. Matsuno, T., et al., Preparation of injectable 3D-formed beta-tricalcium phosphate bead/alginate composite for bone tissue engineering. Dental Materials Journal,2008.27(6):p.827-834.
47. Hunt, N.C., et al., Encapsulation of fibroblasts causes accelerated alginate hydrogel degradation. Acta Biomaterialia,2010.6(9):p.3649-3656.
48. Wu, C.T., et al., Bioactive inorganic-materials/alginate composite microspheres with controllable drug-delivery ability. Journal of Biomedical Materials Research Part B-Applied Biomaterials,2010.94B(1):p.32-43.
49. Fu, Y.C., et al., Porous bioceramic bead prepared by calcium phosphate with sodium alginate gel and PE powder. Materials Science & Engineering C-Biomimetic and Supramolecular Systems,2008.28(7):p.1149-1158.
50. Koyama, K., et al., Preparation and in Vitro Evaluation of Chitosan-coated Alginate/Calcium Complex Microparticles Loaded with Fluorescein-labeled Lactoferrin. Yakugaku Zasshi-Journal of the Pharmaceutical Society of Japan,2009, 129(12):p.1507-1514.
51. Spicer, P.P. and A.G. Mikos, Fibrin glue as a drug delivery system. Journal of Controlled Release,2010.148(1):p.49-55.
52. Yang, Y, et al., Development and evaluation of silk fibroin-based nerve grafts used for peripheral nerve regeneration. Biomaterials,2007.28(36):p.5526-5535.
53. Yeo, J.H., et al., Simple preparation and characteristics of silk fibroin microsphere. European Polymer Journal,2003.39(6):p.1195-1199.
54. Meinel, L., et al., Silk implants for the healing of critical size bone defects. Bone, 2005.37(5):p.688-698.
55. Morita, Y., et al., Frictional properties of regenerated cartilage in vitro. Journal of Biomechanics,2006.39(1):p.103-109.
56.熊思勇,李明忠,用丝素水溶液制备三维生物材料支架.国外丝绸,2009.5：p.1-4.
57. Pritchard, E.M., et al., Incorporation of proteinase inhibitors into silk-based delivery devices for enhanced control of degradation and drug release. Biomaterials, 2011.32(3):p.909-918.
58. Witso, E., et al., Cortical allograft as a vehicle for antibiotic delivery. Acta Orthopaedica,2005.76(4):p.481-486.
59. Ueng, S.W.N., et al., Development of a biodegradable alginate carrier system for antibiotics and bone cells. Journal of Orthopaedic Research,2007.25(1):p.62-72.
60. Benghuzzi, H., et al., Targeted sustained delivery of tobramycin at the site of a femoral osteotomy, in Biomedical Sciences Instrumentation, Vol 42, L. Waite, Editor. 2006, Instrument Soc Amer:Research Triangle Park. p.530-535.
61. Galjour, C., et al., Stimulation of fracture healing by continuous delivery of demineralized bone matrix proteins and tobramycin, in Biomedical Sciences Instrumentation, J. Gillette, Editor.2005, Instrument Soc Amer. p.122-127.
62. Makarov, C., et al., Vancomycin release from bioresorbable calcium phosphate-polymer composites with high ceramic volume fractions. Journal of Materials Science,2010.45(23):p.6320-6324.
63. Kelly, H.M., et al., Formulation and preliminary in vivo dog studies of a novel drug delivery system for the treatment of periodontitis. International Journal of Pharmaceutics,2004.274(1-2):p.167-183.
64.霍美蓉等.紫杉醇阴离子壳聚糖胶束的制备及其小鼠体内组织分布研究.中国药学杂志,2006(24)：p.1876-1880.
65.许向阳等,肿瘤靶向载体N-正辛基-N'-琥珀酰基壳聚糖的制备和结构表征.中国药科大学学报,2007(1)：p.17-20.
66.吴萍等,基于壳聚糖载体的蛋白质药物纳米颗粒制备研究.湖南大学学报(自然科学版),2007.34(9)：p.71-73.
67. Tang X, D.F., Yang Y, Hu N, Gi X., Evaluation of in vitro biocompatibility of silk fibroin-based biomaterials with primarily cultured hippocampal neurons. Journal of Biomedical Material Research A,2009.91 A:p.166-174.
68. Altman GH, D.F., Jakuba C, Calabro T, Horan RL, Chen J, et al., Silk-based biomaterials. Biomaterials,2003.24:p.401-416.
69. Hofmann S, F.S., Rossetti F, Textor M, Vunjak-Novakovic G, Kaplan DL, Silk fibroin as an organic polymer for controlled drug delivery. Journal of Controlled Release,2006. 111:p.219-227.
70. Wang X, W.E., Matsumoto A, Meinel L, Li C, Kaplan DL, Silk micro spheres for encapsulation and controlled release. Journal of Controlled Release,2007.117:p. 360-370.
71. Lammel AS, H.X., Park S-H, Kaplan DL, Scheibel TR, Controlling silk fibroin particle features for drug delivery. Biomaterials,2010.31:p.4583-4591.
72. Wang, X., Hu, X., Daley, A., Rabotyagova, O., Cebe, P., Kaplan, D.L., Nanolayer biomaterial coatings of silk fibroin for controlled release. J Control Release,2007. 121:p.190-199.
73. Pritchard, E., Szybala C, Boison D, Kaplan DL, Silk fibroin encapsulated reservoirs for sustained release of adenosine. Journal of Controlled Release 2010.144: p.159-167.
74. Yaszemski MJ, P.R., Hayes WC, Langer R, Mikos AG, Evolution of bone transplantation:molecular, cellular and tissue strategies to engineer human bone. Biomaterials,1996.17:p.175-185.
75. Aronin, C.E.P., et al., The enhancement of bone allograft incorporation by the local delivery of the sphingosine 1-phosphate receptor targeted drug FTY720. Biomaterials,2010.31(25):p.6417-6424.
76. Walter DH, R.U., Reinhold J, Seeger F, Aicher A, Urbich C, et al., Sphingosine-1-phosphate stimulates the functional capacity of progenitor cells by activation of the CXCR4-dependent signaling pathway via the S1P3 receptor. Arteriosclerosis thrombosis and vascular biology 2007.27:p.275-282.
77. Wamhoff BR, L.K., Macdonald TL, Owens GK, Sphingosine-1-phosphate receptor subtypes differentially regulate smooth muscle cell phenotype. Arteriosclerosis thrombosis and vascular biology 2008.28:p.1454-1461.
78. Vallet-Regi, M., et al., A new property of MCM-41:Drug delivery system. Chemistry of Materials,2001.13(2):p.308-311.
79. Cauda, V., et al., SBA-15 ordered mesoporous silica inside a bioactive glass-ceramic scaffold for local drug delivery. Journal of Materials Science-Materials in Medicine,2008.19(10):p.3303-3310.
80. Seunarine, K., et al.,3D polymer scaffolds for tissue engineering. Nanomedicine, 2006.1(3):p.281-296.
1. May, J.W., et al., Clinical classification of post-traumatic tibial osteomyelitis. Journal of Bone and Joint Surgery-American Volume,1989.71A(9):p.1422-1428.
2. Wilson, M., K. Kelley, and T. Thornhill, Infection as a complication of total kneereplacement arthroplasty. Risk factors and treatment in sixty-seven cases. Journal of Bone and Joint Surgery Am,1990.72(6):p.878-883.
3. Salvati, E., R. Robinson, and S. Zeno, et al., Infection rates after 3175 hip and total knee replacements performed with and without a horizontal unidirectional filtered air-flow system. Journal of Bone and Joint Surgery Am,1982.64(4):p. 525-535.
4. Hanssen, A. and J. Rand, Evaluation and treatment of infection at the site of a total hip or knee arthroplasty. Instrument Course Lecture,1999.48:p.111-122.
5. Fitzgerald, R.J., Total hip arthroplasty sepsis. Prevention and diagnosis. Orthopaedic Clinics of North America,1992.23(2):p.259-264.
6. Wilson, P.J., H. Amstutz, and A. Czerniecki, et al., Total hip replacement with fixation by acrylic cement. A preliminary study of 100 consecutive McKee-Farrar prosthetic replacements. Journal of Bone and Joint Surgery Am,1972.54(2):p. 207-236.
7. He, Y., et al., Effect of antibiotics on the properties of poly(methylmethacrylate)-based bone cement. Journal of Biomedical Materials Research,2002.63(6):p.800-806.
8. Mader, J.T., et al., Antimicrobial treatment of chronic osteomyelitis. Clinical Orthopaedics and Related Research,1999(360):p.47-65.
9. Nikkola, L., P. Viitanen, and N. Ashammakhi, Temporal Control of Drug Release From Biodegradable Polymer:Multicomponent Diclofenac Sodium Releasing PLGA 80/20 Rod. Journal of Biomedical Materials Research Part B-Applied Biomaterials, 2009.89B(2):p.518-526.
10. Schnieders, J., et al., Controlled release of gentamicin from calcium phosphate-poly(lactic acid-co-glycolic acid) composite bone cement. Biomaterials,2006.27(23): p.4239-4249.
11. Walenkamp, G., Self-mixed antibiotic bone cement:western countries learn from developing countries. Acta Orthopaedica,2009.80(5):p.505-507.
12. Meng, Z.X., et al., Fabrication, characterization and in vitro drug release behavior of electrospun PLGA/chitosan nanofibrous scaffold. Materials Chemistry and Physics, 2011.125(3):p.606-611.
13. Neut, D., et al., The effect of mixing on gentamicin release from polymethylmethacrylate bone cements. Acta Orthopaedica Scandinavica,2003.74(6): p.670-676.
14. Rasyid, H.N., et al., Concepts for increasing gentamicin release from handmade bone cement beads. Acta Orthopaedica,2009.80(5):p.508-513.
15. Lazzarini, L., J.T. Mader, and J.H. Calhoun, Osteomyelitis in long bones. Journal of Bone and Joint Surgery-American Volume,2004.86A(10):p.2305-2318.
16. Draget, K.I., G. SkjakBraek, and O. Smidsrod, Alginate based new materials. International Journal of Biological Macromolecules,1997.21(1-2):p.47-55.
17. Matsuno, T., et al., Preparation of injectable 3D-formed beta-tricalcium phosphate bead/alginate composite for bone tissue engineering. Dental Materials Journal,2008. 27(6):p.827-834.
18. Hunt, N.C., et al., Encapsulation of fibroblasts causes accelerated alginate hydrogel degradation. Acta Biomaterialia,2010.6(9):p.3649-3656.
19. Zhao, J., et al., Preparation of bioactive porous HA/PCL composite scaffolds. Applied Surface Science,2008.255(5):p.2942-2946.
20. Berrabah, M. and A. Zahidi, Preparation of poly-epsilon-caprolactone nanocapsules by nanoprecipitation and evaluation of benzyl benzoate by GC-MS. Journal de Pharmacie Clinique,1999.18(4):p.313-317.
21. Lenglet, S., S.M. Li, and M. Vert, Lipase-catalysed degradation of copolymers prepared from epsilon-caprolactone and DL-lactide. Polymer Degradation and Stability,2009.94(4):p.688-692.
22. Wu, C.T., et al., Bioactive inorganic-materials/alginate composite microspheres with controllable drug-delivery ability. Journal of Biomedical Materials Research Part B-Applied Biomaterials,2010.94B(1):p.32-43.
23. Fu, Y.C., et al., Porous bioceramic bead prepared by calcium phosphate with sodium alginate gel and PE powder. Materials Science & Engineering C-Biomimetic and Supramolecular Systems,2008.28(7):p.1149-1158.
24. Koyama, K., et al., Preparation and in Vitro Evaluation of Chitosan-coated Alginate/Calcium Complex Microparticles Loaded with Fluorescein-labeled Lactoferrin. Yakugaku Zasshi-Journal of the Pharmaceutical Society of Japan,2009. 129(12):p.1507-1514.
25. Riyajan, S.A. and J.T. Sakdapipanich, Development of a controlled release neem capsule with a sodium alginate matrix, crosslinked by glutaraldehyde and coated with natural rubber. Polymer Bulletin,2009.63(4):p.609-622.
26. Zhao, J., et al., The influence of polymer concentrations on the structure and mechanical properties of porous polycaprolactone-coated hydroxyapatite scaffolds. Applied Surface Science,2010.256(14):p.4586-4590.
27. Xue, W.C., A. Bandyopadhyay, and S. Bose, Polycaprolactone Coated Porous Tricalcium Phosphate Scaffolds for Controlled Release of Protein for Tissue Engineering. Journal of Biomedical Materials Research Part B-Applied Biomaterials, 2009.91B(2):p.831-838.
28. Ueng, S.W.N., et al., Biodegradable alginate antibiotic beads. Clinical Orthopaedics and Related Research,2000(380):p.250-259.
1. S. Srivastava and N. A. Kotov Composite Layer-by-Layer (LBL) Assembly with Inorganic Nanoparticles and Nanowires [J] Accounts of Chemical Research 2008, 41(12):1831-1841.
2. L. Addadi, D. Joester, F. Nudelman and S. Weiner Mollusk shell formation:A source of new concepts for understanding biomineralization processes [J] Chemistry-a European Journal 2006,12(4):981-987.
3. H. W. Kang, Y Tabata and Y. Ikada Fabrication of porous gelatin scaffolds for tissue engineering [J] Biomaterials 1999,20(14):1339-1344.
4. S. V. Madihally and H. W. T. Matthew Porous chitosan scaffolds for tissue engineering [J] Biomaterials 1999,20(12):1133-1142. 5. H. M. Kelly, P. B. Deasy, E. Ziaka and N. Claffey Formulation and preliminary in
vivo dog studies of a novel drug delivery system for the treatment of periodontitis [J] International Journal of Pharmaceutics 2004,274(1-2):167-183.
6. P. Periti, E. Mini and G. Mosconi Antimicrobial prophylaxis in orthopaedic surgery:the role of teicoplanin (vol 41, pg 329,1988) [J] Journal of Antimicrobial Chemotherapy 1998,42(5):682-682.
7. C. C. Chang and K. Merritt Infection at the site of implanted materials with and without preadhered bacteria [J] Journal of Orthopaedic Research 1994,12(4): 526-531.
8. Y. Suzuki, M. Tanihara, Y. Nishimura, K. Suzuki, Y. Kakimaru and Y. Shimizu A new drug delivery system with controlled release of antibiotic only in the presence of infection [J] Journal of Biomedical Materials Research 1998,42(1):112-116.
9. F. Zhao, Y. Yin, W. W. Lu, J. C. Leong, W. Zhang and J. e. a. Zhang, pp.-3234 Preparation and histological evaluation of biomimetic three-dimensional hydroxyapatite/chitosan-gelatin network composite scaffolds [J] Biomaterials 2002, 23(15):3227-3234.
10. S. Park, J. Park, H. Kim, M. Song and H. Suh Characterization of porous collagen/hyaluronic acid scaffold modified by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide cross-linking [J] Biomaterials 2002, 23(4):1205-1212.
11. V. Karageorgiou and D. Kaplan Porosity of 3D biornaterial scaffolds and osteogenesis [J] Biomaterials 2005,26(27):5474-5491.
12. N. C. Braier and R. A. Jishi Density functional studies of Cu2+ and Ni2+ binding to chitosan [J] Journal of Molecular Structure-Theochem 2000,499(51-55.
13. A. Slovikova, L. Vojtova and J. Jancar Preparation and modification of collagen-based porous scaffold for tissue engineering [J] Chemical Papers 2008,62(4): 417-422.
14. S. Miot, T. Woodfield, A. U. Daniels, R. Suetterlin, I. Peterschmitt, M. Heberer, C. A. van Blitterswijk, J. Riesle and I. Martin Effects of scaffold composition and architecture on human nasal chondrocyte redifferentiation and cartilaginous matrix deposition [J] Biomaterials 2005,26(15):2479-2489.
15. P. B. Olivia Felt, Robert Gurny Chitosan:A Unique Polysaccharide for Drug Delivery [J] Drug Development and Industrial Pharmacy 1998, Vol.24(No.11): Pages 979-993.
16. S. M. Kuo, S. J. Chang, G. C. C. Niu, C. W. Lan, W. T. Cheng and C. Z. Yang Guided Tissue Regeneration with Use of beta-TCP/Chitosan Composite Membrane [J] Journal of Applied Polymer Science 2009,112(5):3127-3134.
17. R. Kormey, N. Peppas and R. Gumy Mechanisms of solute release from prous hydrophilic polymer [J] International Journal of Pharmaceutics 1983,15(1):25.
18. W. W. Thein-Han, J. Saikhun, C. Pholpramoo, R. D. K. Misra and Y. Kitiyanant Chitosan-gelatin scaffolds for tissue engineering:Physico-chemical properties and biological response of buffalo embryonic stem cells and transfectant of GFP-buffalo embryonic stem cells [J] Acta Biomaterialia 2009,5(9):3453-3466.
19. M. Takechi, Y. Miyamoto, Y. Momota, T. Yuasa, S. Tatehara, M. Nagayama, K. Ishikawa and K. Suzuki The in vitro antibiotic release from anti-washout apatite cement using chitosan [J] Journal of Material Science and Material Medicine 2002, 13(973-978.
20. M. Zilberman and J. J. Elsner Antibiotic-eluting medical devices for various applications [J] Journal of Controlled Release 2008,130(3):202-215.
21. L. S. Nair and C. T. Laurencin Biodegradable polymers as biomaterials [J] Progress in Polymer Science 32(8-9):762-798.
22. Q. Zou, Y. B. Li, L. Zhang, Y. Zuo, J. F. Li and J. D. Li Antibiotic delivery system using nano-hydroxyapatite/chitosan bone cement consisting of berberine [J] Journal of Biomedical Materials Research Part A 2009,89A(4):1108-1117.
1. May, J.W., et al., Clinical classification of post-traumatic tibial osteomyelitis. Journal of Bone and Joint Surgery-American Volume,1989.71A(9):p.1422-1428.
2. He, Y., et al., Effect of antibiotics on the properties of poly(methylmethacrylate)-based bone cement. Journal of Biomedical Materials Research,2002.63(6):p.800-806.
3. Mader, J.T., et al., Antimicrobial treatment of chronic osteomyelitis. Clinical Orthopaedics and Related Research,1999(360):p.47-65.
4. Nikkola, L., P. Viitanen, and N. Ashammakhi, Temporal Control of Drug Release From Biodegradable Polymer:Multicomponent Diclofenac Sodium Releasing PLGA 80/20 Rod. Journal of Biomedical Materials Research Part B-Applied Biomaterials, 2009.89B(2):p.518-526.
5. Schnieders, J., et al., Controlled release of gentamicin from calcium phosphate-poly(lactic acid-co-glycolic acid) composite bone cement. Biomaterials,2006.27(23): p.4239-4249.
6. Walenkamp, G., Self-mixed antibiotic bone cement:western countries learn from developing countries. Acta Orthopaedica,2009.80(5):p.505-507.
7. Meng, Z.X., et al., Fabrication, characterization and in vitro drug release behavior of electrospun PLGA/chitosan nanofibrous scaffold. Materials Chemistry and Physics,2011.125(3):p.606-611.
8. Neut, D., et al., The effect of mixing on gentamicin release from polymethylmethacrylate bone cements. Acta Orthopaedica Scandinavica,2003.74(6): p.670-676.
9. Rasyid, H.N., et al., Concepts for increasing gentamicin release from handmade bone cement beads. Acta Orthopaedica,2009.80(5):p.508-513.
10. De, P., et al., Structure-release rate correlation in collagen gels containing fluorescent drug analogs. Biomaterials,2005.26:p.7164-72.
11. Langer, R., Invited review:polymeric delivery systems for controlled drug release. Chemical Engineering Comminication,1980.6.
12. Parsons, B. and E. Strauss, Surgical management of chronic osteomyelitis. American Journal of Surgery,2004.188(1A):p.57S-66S.
13. Shirtliff, M.E., J.H. Calhoun, and J.T. Mader, Experimental osteomyelitis treatment with antibiotic-impregnated hydroxyapatite. Clinical Orthopaedics and Related Research,2002(401):p.239-247.
14. Javed, S. and K. Kohli, Local Delivery of Minocycline Hydrochloride:A Therapeutic Paradigm in Periodontal Diseases. Current Drug Delivery,2010.7(5):p. 398-406.
15. McLaren, A.C., Alternative materials to acrylic bone cement for delivery of depot antibiotics in orthopaedic infections. Clinical Orthopaedics and Related Research, 2004(427):p.101-106.
16. Thein-Han, W.W., et al., Chitosan-gelatin scaffolds for tissue engineering: Physico-chemical properties and biological response of buffalo embryonic stem cells and transfectant of GFP-buffalo embryonic stem cells. Acta Biomaterialia,2009.5(9): p.3453-3466.
17. Sevy, J.O., et al., Assay method for polymer-controlled antibiotic release from allograft bone to target orthopaedic infections-biomed 2010. Biomed Sci Instrum, 2010.46:p.136-41.
18. Prabu, P., et al., Preparation and drug release activity of scaffolds containing collagen and poly(caprolactone). Journal of Biomedical Materials Research Part A, 2006.79A(1):p.153-158.
19. Roseman, T. and W. Higuchi, Release of medroxyprogesterone acetate from a silicone polymer. Journal of Pharmaceutical Science,1970.59:p.353-357.
20. Chandrasekaran, S. and D. Paul, Dissolution-controlled transport from dispersed matrixes. Journal of Pharmaceutical Science,1982.71(12):p.1339-1402.
21. Peppas, N., ed. Athematical modeling of diffusion process in drug delivery polymeric systems. Controlled Drug Bioavailability ed. V. Smolen and L. Ball. Vol.1. 1984, John Wiley and Sons:New York.203-237.
22. Verguaud, J., ed. Controlled Drug Release of Oral Dosage Forms.1993, Ellis Horwood:New York.21-390.
23. Narasimhan, B. and N. Peppas, eds. The role of modeling studies in the development of future controlled-release devices. Controlled Drug Delivery, ed. K. Park.1997, ACS:Washington, DC.529-555.
24.高秋明and刘兴炎,慢性骨髓炎的治疗.中国矫形外科杂志,2002.10(11)：p.1120-1121.
25. Mackey, D., A. Varlet, and D. Debeaumont, Antibiotic loaded plaster of Paris pellets:an in vitro study of a possible method of local antibiotic therapy in bone infection. Clinical Orthopaedics,1982((167):p.263-8.
26. Mcnally, M., J. Small, and H.e.a. Tofighi, Two-stage management of chronic osteomyelitis of the long bones. Journal of Bone and Joint Surgery,1993.75:p.375-380.
27. Chan, Y., W. Ueng, and C. Wang, Management of small infected tibial defects with antibiotic-impregnated autogenic cancellous bone grafting. Journal of traumatology,1998,45(4):p.758-764.
1. J. W. May, J. B. Jupiter, A. J. Weiland and H. S. Byrd, Clinical classification of post-traumatic tibial osteomyelitis. [J] Journal of Bone and Joint Surgery-American Volume 1989,71A(9):1422-1428.
2. M. Wilson, K. Kelley and T. Thornhill, Infection as a complication of total kneereplacement arthroplasty. Risk factors and treatment in sixty-seven cases.. [J] Journal of Bone and Joint Surgery Am 1990,72(6):878-883.
3. E. Salvati, R. Robinson and S. Zeno, et al., Infection rates after 3175 hip and total knee replacements performed with and without a horizontal unidirectional filtered air-flow system. [J] Journal of Bone and Joint Surgery Am 1982,64(4): 525-535.
4. A. Hanssen and J. Rand, Evaluation and treatment of infection at the site of a total hip or knee arthroplasty. [J] Instrument Course Lecture 1999,48(111-122.
5. R. J. Fitzgerald, Total hip arthroplasty sepsis. Prevention and diagnosis. [J] Orthopaedic Clinics of North America 1992,23(2):259-264.
6. P. J. Wilson, H. Amstutz and A. Czerniecki, et al., Total hip replacement with fixation by acrylic cement. A preliminary study of 100 consecutive McKee-Farrar prosthetic replacements. [J] Journal of Bone and Joint Surgery Am 1972,54(2): 207-236.
7. D. G. Barrett and M. N. Yousaf, Design and Applications of Biodegradable Polyester Tissue Scaffolds Based on Endogenous Monomers Found in Human Metabolism. [J] Molecules 2009,14(10):4022-4050.
8. F. Couet, N. Rajan and D. Mantovani, Macromolecular biomaterials for scaffold-based vascular tissue engineering. [J] Macromolecular Bioscience 2007,7(5): 701-718.
9. E. Witso, L. Persen, P. Benum and K. Bergh, Cortical allograft as a vehicle for antibiotic delivery. [J] Acta Orthopaedica 2005,76(4):481-486.
10. L. Meinel, R. Fajardo, S. Hofmann, R. Langer, J. Chen, B. Snyder, G. Vunjak-Novakovic and D. Kaplan, Silk implants for the healing of critical size bone defects. [J] Bone 2005,37(5):688-698.
11. J. H. Yeo, K. G. Lee, Y. W. Lee and S. Y. Kim, Simple preparation and characteristics of silk fibroin microsphere. [J] European Polymer Journal 2003,39(6): 1195-1199.
12. Y. Yang, F. Ding, H. Wu, W. Hu, W. Liu, H. Liu and X. Gu, Development and evaluation of silk fibroin-based nerve grafts used for peripheral nerve regeneration. [J] Biomaterials 2007,28(36):5526-5535.
13. Y. Morita, N. Tomita, H. Aoki, M. Sonobe, S. Wakitani, Y. Tamada, T. Suguro and K. Ikeuchi, Frictional properties of regenerated cartilage in vitro. [J] Journal of Biomechanics 2006,39(1):103-109.
14. M. Chevillard, P. Couble and J. C. Prudhomme, COMPLETE NUCLEOTIDE-SEQUENCE OF THE GENE ENCODING THE BOMBYX-MORISILK PROTEIN-P25 AND PREDICTED AMINO-ACID-SEQUENCE OF THEPROTEIN. [J] Nucleic Acids Research 1986,14(15):6341-6342.
15. K. Tanaka, N. Kajiyama, K. Ishikura, S. Waga, A. Kikuchi, K. Ohtomo, T. Takagi and S. Mizuno, Determination of the site of disulfide linkage between heavy and light chains of silk fibroin produced by Bombix mori. [J] Biochimica Et Biophysica Acta-Protein Structure and Molecular Enzymology 1999,1432(1):92-103.
16. C. Z. Zhou, F. Confalonieri, M. Jacquet, R. Perasso, Z. G. Li and J. Janin, Silk fibroin:Structural implications of a remarkable amino acid sequence. [J] Proteins-Structure Function and Genetics 2001,44(2):119-122.
17.熊思勇,李明忠,用丝素水溶液制备三维生物材料支架.[J]国外丝绸2009,5：1-4.
18. E. M. Pritchard, T. Valentin, D. Boison and D. L. Kaplan, Incorporation of proteinase inhibitors into silk-based delivery devices for enhanced control of degradation and drug release. [J] Biomaterials 2011,32(3):909-918.
19. V. Karageorgiou and D. Kaplan, Porosity of 3D biornaterial scaffolds and osteogenesis. [J] Biomaterials 2005,26(27):5474-5491.
20.曹正兵,[J]复旦大学博士学位论文2005.
1. Krasko, M.Y., et al., Gentamicin extended release from an injectable polymeric implant. Journal of Controlled Release,2007.117(1):p.90-96.
2. Schnieders, J., et al., Controlled release of gentamicin from calcium phosphate-poly(lactic acid-co-glycolic acid) composite bone cement. Biomaterials,2006.27(23): p.4239-4249.
3. Hendricks, K.J., et al., Elution characteristics of tobramycin from polycaprolactone in a rabbit model. Clinical Orthopaedics and Related Research, 2001(392):p.418-426.
4. Foster, L.J.R., et al., Chitosan-Vancomysin Composite Biomaterial as a Laser Activated Surgical Adhesive with Regional Antimicrobial Activity. Biomacromolecules, 2010.11(12):p.3563-3570.
5. Sarasam, A., et al., Antibacterial activity of chitosan-based matrices on oral pathogens. Journal of Materials Science:Materials in Medicine,2008.19(3):p. 1083-1090.
6. Bleier, B.S., et al., Antibiotic eluting chitosan glycerophosphate implant in the setting of acute bacterial sinusitis:A rabbit model. American Journal of Rhinology & Allergy,2010.24(2):p.129-132.
7. Draget, K.I., G. SkjakBraek, and O. Smidsrod, Alginate based new materials. International Journal of Biological Macromolecules,1997.21(1-2):p.47-55.
8. Matsuno, T., et al., Preparation of injectable 3D-formed beta-tricalcium phosphate bead/alginate composite for bone tissue engineering. Dental Materials Journal,2008.27(6):p.827-834.
9. Hunt, N.C., et al., Encapsulation of fibroblasts causes accelerated alginate hydrogel degradation. Acta Biomaterialia,2010.6(9):p.3649-3656.
10. Wu, C.T., et al., Bioactive inorganic-materials/alginate composite microspheres with controllable drug-delivery ability. Journal of Biomedical Materials Research Part B-Applied Biomaterials,2010.94B(1):p.32-43.
11. Fu, Y.C., et al., Porous bioceramic bead prepared by calcium phosphate with sodium alginate gel and PE powder. Materials Science & Engineering C-Biomimetic and Supramolecular Systems,2008.28(7):p.1149-1158.
12. Koyama, K., et al., Preparation and in Vitro Evaluation of Chitosan-coated Alginate/Calcium Complex Microparticles Loaded with Fluorescein-labeled Lactoferrin. Yakugaku Zasshi-Journal of the Pharmaceutical Society of Japan,2009. 129(12):p.1507-1514.
13. Spicer, P.P. and A.G. Mikos, Fibrin glue as a drug delivery system. Journal of Controlled Release,2010.148(1):p.49-55.
14. Yang, Y, et al., Development and evaluation of silk fibroin-based nerve grafts used for peripheral nerve regeneration. Biomaterials,2007.28(36):p.5526-5535.
15. Yeo, J.H., et al., Simple preparation and characteristics of silk fibroin microsphere. European Polymer Journal,2003.39(6):p.1195-1199.
16. Meinel, L., et al., Silk implants for the healing of critical size bone defects. Bone, 2005.37(5):p.688-698.
17. Morita, Y, et al., Frictional properties of regenerated cartilage in vitro. Journal of Biomechanics,2006.39(1):p.103-109.
18. Pritchard, E.M., et al., Incorporation of proteinase inhibitors into silk-based delivery devices for enhanced control of degradation and drug release. Biomaterials, 2011.32(3):p.909-918.
19. Witso, E., et al., Cortical allograft as a vehicle for antibiotic delivery. Acta Orthopaedica,2005.76(4):p.481-486.
20. Ueng, S.W.N., et al., Development of a biodegradable alginate carrier system for antibiotics and bone cells. Journal of Orthopaedic Research,2007.25(1):p.62-72.
21. Benghuzzi, H., et al., Targeted sustained delivery of tobramycin at the site of a femoral osteotomy, in Biomedical Sciences Instrumentation, Vol 42, L. Waite, Editor. 2006, Instrument Soc Amer:Research Triangle Park. p.530-535.
22. Galjour, C., et al., Stimulation of fracture healing by continuous delivery of demineralized bone matrix proteins and tobramycin, in Biomedical Sciences Instrumentation, J. Gillette, Editor.2005, Instrument Soc Amer. p.122-127.
23. Makarov, C., et al., Vancomycin release from bioresorbable calcium phosphate-polymer composites with high ceramic volume fractions. Journal of Materials Science,2010.45(23):p.6320-6324.
2. Zimmerli, W., A. Trampuz, and P.E. Ochsner, Current concepts:Prosthetic-joint infections. New England Journal of Medicine,2004.351(16):p.1645-1654.
3. Widmer, A.F., New developments in diagnosis and treatment of infection in orthopedic implants. Clinical Infectious Diseases,2001.33:p. S94-S106.
4. Kilgus, D.J., D.J. Howe, and A. Strang, Results of periprosthetic hip and knee infections caused by resistant bacteria. Clinical Orthopaedics and Related Research, 2002(404):p.116-124.
5. Proctor, R.A., et al., Small colony variants:a pathogenic form of bacteria that facilitates persistent and recurrent infections. Nature Reviews Microbiology,2006. 4(4):p.295-305.
6. Betsch, B.Y., et al., Treatment of joint prosthesis infection in accordance with current recommendations improves outcome. Clinical Infectious Diseases,2008.46(8): p.1221-1226.
7. Salgado, C.D., et al., Higher risk of failure of methicillin-resistant Staphylococcus aureus prosthetic joint infections. Clinical Orthopaedics and Related Research, 2007(461):p.48-53.
8. Soriano, A., et al., Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia. Clinical Infectious Diseases,2008.46(2):p.193-200.
9. Radin, S., et al., Calcium phosphate ceramic coatings as carriers of vancomycin. Biomaterials,1997.18(11):p.777-782.
10. Feng, K., et al., Novel antibacterial nanofibrous PLLA scaffolds. Journal of Controlled Release,2010.146(3):p.363-369.
11. Ozkan, S., D.M. Kalyon, and X.J. Yu, Functionally graded beta-TCP/PCL nanocomposite scaffolds:In vitro evaluation with human fetal osteoblast cells for bone tissue engineering. Journal of Biomedical Materials Research Part A,2010. 92A(3):p.1007-1018.
12. Waldvoge.Fa, G. Medoff, and M.N. Swartz, Osteomyelitis:a review of clinical features, therapeutic considerations and unusual aspects. New England Journal of Medicine,1970.282(4):p.198-206.
13. Cierny, G., J.T. Mader, and J.J. Penninck, A clinical staging system for adult osteomyelitis. Clinical Orthopaedics and Related Research,2003(414):p.7-24.
14. Chang, W., et al., Adult osteomyelitis:Debridement versus debridement plus Osteoset T (R)pellets. Acta Orthopaedica Belgica,2007.73(2):p.238-243.
15. Dacquet, V., et al., Antibiotic-impregnated plaster of Paris beads-Trials with teicoplanin. Clinical Orthopaedics and Related Research,1992(282):p.241-249.
16. Javed, S. and K. Kohli, Local Delivery of Minocycline Hydrochloride:A Therapeutic Paradigm in Periodontal Diseases. Current Drug Delivery,2010.7(5):p. 398-406.
17. Sia, I.G. and E.F. Berbari, Osteomyelitis. Best Practice & Research in Clinical Rheumatology,2006.20(6):p.1065-1081.
18. Mader, J.T., et al., Antimicrobial treatment of chronic osteomyelitis. Clinical Orthopaedics and Related Research,1999(360):p.47-65.
19. De, P., et al., Structure-release rate correlation in collagen gels containing fluorescent drug analogs. Biomaterials,2005.26:p.7164-72.
20. Langer, R., Invited review:polymeric delivery systems for controlled drug release. Chemical Engineering Comminication,1980.6.
21. Nikkola, L., P. Viitanen, and N. Ashammakhi, Temporal Control of Drug Release From Biodegradable Polymer:Multicomponent Diclofenac Sodium Releasing PLGA 80/20 Rod. Journal of Biomedical Materials Research Part B-Applied Biomaterials, 2009.89B(2):p.518-526.
22. Buchholz, H.W. and Engelbre.H, Deposit effect of some antibiotics in mixing with artificial resin palacos. Chirurg,1970.41(11):p.511-&.
23. Anguita-Alonso, P., et al., Comparative study of antimicrobial release kinetics from polymethylmethacrylate. Clin Orthop Relat Res,2006.445:p.239-44.
24. Hartley, M.P. and S. Sanderson, Use of antibiotic impregnated polymethylmethacrylate beads for the treatment of chronic mandibular osteomyelitis in a Bennett's wallaby (Macropus rufogriseus rufogriseus). Australian Veterinary Journal,2003.81(12):p.742-744.
25. Scott, D.M., J.C. Rotschafer, and F. Behrens, Use of vancomycin and tobramycin polymethymethacrylate impregnated beads in the management of chronic osteomyelitis Drug Intelligence & Clinical Pharmacy,1988.22(6):p.480-483.
26. Evans, R.P., Successful treatment of total hip and knee infection with articulating antibiotic components-A modified treatment method. Clinical Orthopaedics and Related Research,2004(427):p.37-46.
27. Walenkamp, G., Self-mixed antibiotic bone cement:western countries learn from developing countries. Acta Orthopaedica,2009.80(5):p.505-507.
28. Rasyid, H.N., et al., Concepts for increasing gentamicin release from handmade bone cement beads. Acta Orthopaedica,2009.80(5):p.508-513.
29. Thielen, T., et al., Mechanical behaviour of standardized, endoskeleton-including hip spacers implanted into composite femurs. International Journal of Medical Sciences,2009.6(5):p.280-286.
30. Diez-Pena, E., et al., Gentamicin sulphate release from a modified commercial acrylic surgical radiopaque bone cement. Ⅰ. Influence of the gentamicin concentration on the release process mechanism. Chemical & Pharmaceutical Bulletin,2002.50(9): p.1201-1208.
31. Belt, v.d.H., et al., Surface roughness, porosity and wettability of gentamicin-loaded bone cements and their antibiotic release. Biomaterials,2000.21: p.1981-7.
32. Neut, D., et al., The effect of mixing on gentamicin release from polymethylmethacrylate bone cements. Acta Orthopaedica Scandinavica,2003.74(6): p.670-676.
33. Peltier, L.F., The use of Plaster of Paris to fill defects in bone. Clinical Orthopaedics,1961 ((21):p.1-31.
34. Mackey, D., A. Varlet, and D. Debeaumont, Antibiotic loaded plaster of Paris pellets:an in vitro study of a possible method of local antibiotic therapy in bone infection. Clinical Orthopaedics,1982((167):p.263-8.
35. El-Ghannam, A., K. Jahed, and M. Govindaswami, Resorbable bioactive ceramic for treatment of bone infection. Journal of Biomedical Materials Research Part A, 2010.94A(1):p.308-316.
36. Scharer, B.M. and S.M. Sanicola, The In Vitro Elution Characteristics of Vancomycin From Calcium Phosphate-Calcium Sulfate Beads. Journal of Foot & Ankle Surgery,2009.48(5):p.540-542.
37. Gautier, H., et al., In vitro characterisation of calcium phosphate biomaterials loaded with lidocaine hydrochloride and morphine hydrochloride. Journal of Materials Science-Materials in Medicine,2010.21(12):p.3141-3150.
38. Sanicola, S.M. and S.F. Albert, The in vitro elution characteristics of vancomycin and tobramycin from calcium sulfate beads. The Journal of Foot and Ankle Surgery. 44(2):p.121-124.
39. Krasko, M.Y., et al., Gentamicin extended release from an injectable polymeric implant. Journal of Controlled Release,2007.117(1):p.90-96.
40. Schnieders, J., et al., Controlled release of gentamicin from calcium phosphate poly(lactic acid-co-glycolic acid) composite bone cement. Biomaterials,2006.27(23): p.4239-4249.
41. Hendricks, K.J., et al., Elution characteristics of tobramycin from polycaprolactone in a rabbit model. Clinical Orthopaedics and Related Research, 2001(392):p.418-426.
42. Foster, L.J.R., et al., Chitosan-Vancomysin Composite Biomaterial as a Laser Activated Surgical Adhesive with Regional Antimicrobial Activity. Biomacromolecules, 2010.11(12):p.3563-3570.
43. Sarasam, A., et al., Antibacterial activity of chitosan-based matrices on oral pathogens. Journal of Materials Science:Materials in Medicine,2008.19(3):p. 1083-1090.
44. Bleier, B.S., et al., Antibiotic eluting chitosan glycerophosphate implant in the setting of acute bacterial sinusitis:A rabbit model. American Journal of Rhinology & Allergy,2010.24(2):p.129-132.
45. Draget, K.I., G. SkjakBraek, and O. Smidsrod, Alginate based new materials. International Journal of Biological Macromolecules,1997.21(1-2):p.47-55.
46. Matsuno, T., et al., Preparation of injectable 3D-formed beta-tricalcium phosphate bead/alginate composite for bone tissue engineering. Dental Materials Journal,2008.27(6):p.827-834.
47. Hunt, N.C., et al., Encapsulation of fibroblasts causes accelerated alginate hydrogel degradation. Acta Biomaterialia,2010.6(9):p.3649-3656.
48. Wu, C.T., et al., Bioactive inorganic-materials/alginate composite microspheres with controllable drug-delivery ability. Journal of Biomedical Materials Research Part B-Applied Biomaterials,2010.94B(1):p.32-43.
49. Fu, Y.C., et al., Porous bioceramic bead prepared by calcium phosphate with sodium alginate gel and PE powder. Materials Science & Engineering C-Biomimetic and Supramolecular Systems,2008.28(7):p.1149-1158.
50. Koyama, K., et al., Preparation and in Vitro Evaluation of Chitosan-coated Alginate/Calcium Complex Microparticles Loaded with Fluorescein-labeled Lactoferrin. Yakugaku Zasshi-Journal of the Pharmaceutical Society of Japan,2009, 129(12):p.1507-1514.
51. Spicer, P.P. and A.G. Mikos, Fibrin glue as a drug delivery system. Journal of Controlled Release,2010.148(1):p.49-55.
52. Yang, Y, et al., Development and evaluation of silk fibroin-based nerve grafts used for peripheral nerve regeneration. Biomaterials,2007.28(36):p.5526-5535.
53. Yeo, J.H., et al., Simple preparation and characteristics of silk fibroin microsphere. European Polymer Journal,2003.39(6):p.1195-1199.
54. Meinel, L., et al., Silk implants for the healing of critical size bone defects. Bone, 2005.37(5):p.688-698.
55. Morita, Y., et al., Frictional properties of regenerated cartilage in vitro. Journal of Biomechanics,2006.39(1):p.103-109.
56.熊思勇,李明忠,用丝素水溶液制备三维生物材料支架.国外丝绸,2009.5：p.1-4.
57. Pritchard, E.M., et al., Incorporation of proteinase inhibitors into silk-based delivery devices for enhanced control of degradation and drug release. Biomaterials, 2011.32(3):p.909-918.
58. Witso, E., et al., Cortical allograft as a vehicle for antibiotic delivery. Acta Orthopaedica,2005.76(4):p.481-486.
59. Ueng, S.W.N., et al., Development of a biodegradable alginate carrier system for antibiotics and bone cells. Journal of Orthopaedic Research,2007.25(1):p.62-72.
60. Benghuzzi, H., et al., Targeted sustained delivery of tobramycin at the site of a femoral osteotomy, in Biomedical Sciences Instrumentation, Vol 42, L. Waite, Editor. 2006, Instrument Soc Amer:Research Triangle Park. p.530-535.
61. Galjour, C., et al., Stimulation of fracture healing by continuous delivery of demineralized bone matrix proteins and tobramycin, in Biomedical Sciences Instrumentation, J. Gillette, Editor.2005, Instrument Soc Amer. p.122-127.
62. Makarov, C., et al., Vancomycin release from bioresorbable calcium phosphate-polymer composites with high ceramic volume fractions. Journal of Materials Science,2010.45(23):p.6320-6324.
63. Kelly, H.M., et al., Formulation and preliminary in vivo dog studies of a novel drug delivery system for the treatment of periodontitis. International Journal of Pharmaceutics,2004.274(1-2):p.167-183.
64.霍美蓉等.紫杉醇阴离子壳聚糖胶束的制备及其小鼠体内组织分布研究.中国药学杂志,2006(24)：p.1876-1880.
65.许向阳等,肿瘤靶向载体N-正辛基-N'-琥珀酰基壳聚糖的制备和结构表征.中国药科大学学报,2007(1)：p.17-20.
66.吴萍等,基于壳聚糖载体的蛋白质药物纳米颗粒制备研究.湖南大学学报(自然科学版),2007.34(9)：p.71-73.
67. Tang X, D.F., Yang Y, Hu N, Gi X., Evaluation of in vitro biocompatibility of silk fibroin-based biomaterials with primarily cultured hippocampal neurons. Journal of Biomedical Material Research A,2009.91 A:p.166-174.
68. Altman GH, D.F., Jakuba C, Calabro T, Horan RL, Chen J, et al., Silk-based biomaterials. Biomaterials,2003.24:p.401-416.
69. Hofmann S, F.S., Rossetti F, Textor M, Vunjak-Novakovic G, Kaplan DL, Silk fibroin as an organic polymer for controlled drug delivery. Journal of Controlled Release,2006. 111:p.219-227.
70. Wang X, W.E., Matsumoto A, Meinel L, Li C, Kaplan DL, Silk micro spheres for encapsulation and controlled release. Journal of Controlled Release,2007.117:p. 360-370.
71. Lammel AS, H.X., Park S-H, Kaplan DL, Scheibel TR, Controlling silk fibroin particle features for drug delivery. Biomaterials,2010.31:p.4583-4591.
72. Wang, X., Hu, X., Daley, A., Rabotyagova, O., Cebe, P., Kaplan, D.L., Nanolayer biomaterial coatings of silk fibroin for controlled release. J Control Release,2007. 121:p.190-199.
73. Pritchard, E., Szybala C, Boison D, Kaplan DL, Silk fibroin encapsulated reservoirs for sustained release of adenosine. Journal of Controlled Release 2010.144: p.159-167.
74. Yaszemski MJ, P.R., Hayes WC, Langer R, Mikos AG, Evolution of bone transplantation:molecular, cellular and tissue strategies to engineer human bone. Biomaterials,1996.17:p.175-185.
75. Aronin, C.E.P., et al., The enhancement of bone allograft incorporation by the local delivery of the sphingosine 1-phosphate receptor targeted drug FTY720. Biomaterials,2010.31(25):p.6417-6424.
76. Walter DH, R.U., Reinhold J, Seeger F, Aicher A, Urbich C, et al., Sphingosine-1-phosphate stimulates the functional capacity of progenitor cells by activation of the CXCR4-dependent signaling pathway via the S1P3 receptor. Arteriosclerosis thrombosis and vascular biology 2007.27:p.275-282.
77. Wamhoff BR, L.K., Macdonald TL, Owens GK, Sphingosine-1-phosphate receptor subtypes differentially regulate smooth muscle cell phenotype. Arteriosclerosis thrombosis and vascular biology 2008.28:p.1454-1461.
78. Vallet-Regi, M., et al., A new property of MCM-41:Drug delivery system. Chemistry of Materials,2001.13(2):p.308-311.
79. Cauda, V., et al., SBA-15 ordered mesoporous silica inside a bioactive glass-ceramic scaffold for local drug delivery. Journal of Materials Science-Materials in Medicine,2008.19(10):p.3303-3310.
80. Seunarine, K., et al.,3D polymer scaffolds for tissue engineering. Nanomedicine, 2006.1(3):p.281-296.
1. May, J.W., et al., Clinical classification of post-traumatic tibial osteomyelitis. Journal of Bone and Joint Surgery-American Volume,1989.71A(9):p.1422-1428.
2. Wilson, M., K. Kelley, and T. Thornhill, Infection as a complication of total kneereplacement arthroplasty. Risk factors and treatment in sixty-seven cases. Journal of Bone and Joint Surgery Am,1990.72(6):p.878-883.
3. Salvati, E., R. Robinson, and S. Zeno, et al., Infection rates after 3175 hip and total knee replacements performed with and without a horizontal unidirectional filtered air-flow system. Journal of Bone and Joint Surgery Am,1982.64(4):p. 525-535.
4. Hanssen, A. and J. Rand, Evaluation and treatment of infection at the site of a total hip or knee arthroplasty. Instrument Course Lecture,1999.48:p.111-122.
5. Fitzgerald, R.J., Total hip arthroplasty sepsis. Prevention and diagnosis. Orthopaedic Clinics of North America,1992.23(2):p.259-264.
6. Wilson, P.J., H. Amstutz, and A. Czerniecki, et al., Total hip replacement with fixation by acrylic cement. A preliminary study of 100 consecutive McKee-Farrar prosthetic replacements. Journal of Bone and Joint Surgery Am,1972.54(2):p. 207-236.
7. He, Y., et al., Effect of antibiotics on the properties of poly(methylmethacrylate)-based bone cement. Journal of Biomedical Materials Research,2002.63(6):p.800-806.
8. Mader, J.T., et al., Antimicrobial treatment of chronic osteomyelitis. Clinical Orthopaedics and Related Research,1999(360):p.47-65.
9. Nikkola, L., P. Viitanen, and N. Ashammakhi, Temporal Control of Drug Release From Biodegradable Polymer:Multicomponent Diclofenac Sodium Releasing PLGA 80/20 Rod. Journal of Biomedical Materials Research Part B-Applied Biomaterials, 2009.89B(2):p.518-526.
10. Schnieders, J., et al., Controlled release of gentamicin from calcium phosphate-poly(lactic acid-co-glycolic acid) composite bone cement. Biomaterials,2006.27(23): p.4239-4249.
11. Walenkamp, G., Self-mixed antibiotic bone cement:western countries learn from developing countries. Acta Orthopaedica,2009.80(5):p.505-507.
12. Meng, Z.X., et al., Fabrication, characterization and in vitro drug release behavior of electrospun PLGA/chitosan nanofibrous scaffold. Materials Chemistry and Physics, 2011.125(3):p.606-611.
13. Neut, D., et al., The effect of mixing on gentamicin release from polymethylmethacrylate bone cements. Acta Orthopaedica Scandinavica,2003.74(6): p.670-676.
14. Rasyid, H.N., et al., Concepts for increasing gentamicin release from handmade bone cement beads. Acta Orthopaedica,2009.80(5):p.508-513.
15. Lazzarini, L., J.T. Mader, and J.H. Calhoun, Osteomyelitis in long bones. Journal of Bone and Joint Surgery-American Volume,2004.86A(10):p.2305-2318.
16. Draget, K.I., G. SkjakBraek, and O. Smidsrod, Alginate based new materials. International Journal of Biological Macromolecules,1997.21(1-2):p.47-55.
17. Matsuno, T., et al., Preparation of injectable 3D-formed beta-tricalcium phosphate bead/alginate composite for bone tissue engineering. Dental Materials Journal,2008. 27(6):p.827-834.
18. Hunt, N.C., et al., Encapsulation of fibroblasts causes accelerated alginate hydrogel degradation. Acta Biomaterialia,2010.6(9):p.3649-3656.
19. Zhao, J., et al., Preparation of bioactive porous HA/PCL composite scaffolds. Applied Surface Science,2008.255(5):p.2942-2946.
20. Berrabah, M. and A. Zahidi, Preparation of poly-epsilon-caprolactone nanocapsules by nanoprecipitation and evaluation of benzyl benzoate by GC-MS. Journal de Pharmacie Clinique,1999.18(4):p.313-317.
21. Lenglet, S., S.M. Li, and M. Vert, Lipase-catalysed degradation of copolymers prepared from epsilon-caprolactone and DL-lactide. Polymer Degradation and Stability,2009.94(4):p.688-692.
22. Wu, C.T., et al., Bioactive inorganic-materials/alginate composite microspheres with controllable drug-delivery ability. Journal of Biomedical Materials Research Part B-Applied Biomaterials,2010.94B(1):p.32-43.
23. Fu, Y.C., et al., Porous bioceramic bead prepared by calcium phosphate with sodium alginate gel and PE powder. Materials Science & Engineering C-Biomimetic and Supramolecular Systems,2008.28(7):p.1149-1158.
24. Koyama, K., et al., Preparation and in Vitro Evaluation of Chitosan-coated Alginate/Calcium Complex Microparticles Loaded with Fluorescein-labeled Lactoferrin. Yakugaku Zasshi-Journal of the Pharmaceutical Society of Japan,2009. 129(12):p.1507-1514.
25. Riyajan, S.A. and J.T. Sakdapipanich, Development of a controlled release neem capsule with a sodium alginate matrix, crosslinked by glutaraldehyde and coated with natural rubber. Polymer Bulletin,2009.63(4):p.609-622.
26. Zhao, J., et al., The influence of polymer concentrations on the structure and mechanical properties of porous polycaprolactone-coated hydroxyapatite scaffolds. Applied Surface Science,2010.256(14):p.4586-4590.
27. Xue, W.C., A. Bandyopadhyay, and S. Bose, Polycaprolactone Coated Porous Tricalcium Phosphate Scaffolds for Controlled Release of Protein for Tissue Engineering. Journal of Biomedical Materials Research Part B-Applied Biomaterials, 2009.91B(2):p.831-838.
28. Ueng, S.W.N., et al., Biodegradable alginate antibiotic beads. Clinical Orthopaedics and Related Research,2000(380):p.250-259.
1. S. Srivastava and N. A. Kotov Composite Layer-by-Layer (LBL) Assembly with Inorganic Nanoparticles and Nanowires [J] Accounts of Chemical Research 2008, 41(12):1831-1841.
2. L. Addadi, D. Joester, F. Nudelman and S. Weiner Mollusk shell formation:A source of new concepts for understanding biomineralization processes [J] Chemistry-a European Journal 2006,12(4):981-987.
3. H. W. Kang, Y Tabata and Y. Ikada Fabrication of porous gelatin scaffolds for tissue engineering [J] Biomaterials 1999,20(14):1339-1344.
4. S. V. Madihally and H. W. T. Matthew Porous chitosan scaffolds for tissue engineering [J] Biomaterials 1999,20(12):1133-1142. 5. H. M. Kelly, P. B. Deasy, E. Ziaka and N. Claffey Formulation and preliminary in
vivo dog studies of a novel drug delivery system for the treatment of periodontitis [J] International Journal of Pharmaceutics 2004,274(1-2):167-183.
6. P. Periti, E. Mini and G. Mosconi Antimicrobial prophylaxis in orthopaedic surgery:the role of teicoplanin (vol 41, pg 329,1988) [J] Journal of Antimicrobial Chemotherapy 1998,42(5):682-682.
7. C. C. Chang and K. Merritt Infection at the site of implanted materials with and without preadhered bacteria [J] Journal of Orthopaedic Research 1994,12(4): 526-531.
8. Y. Suzuki, M. Tanihara, Y. Nishimura, K. Suzuki, Y. Kakimaru and Y. Shimizu A new drug delivery system with controlled release of antibiotic only in the presence of infection [J] Journal of Biomedical Materials Research 1998,42(1):112-116.
9. F. Zhao, Y. Yin, W. W. Lu, J. C. Leong, W. Zhang and J. e. a. Zhang, pp.-3234 Preparation and histological evaluation of biomimetic three-dimensional hydroxyapatite/chitosan-gelatin network composite scaffolds [J] Biomaterials 2002, 23(15):3227-3234.
10. S. Park, J. Park, H. Kim, M. Song and H. Suh Characterization of porous collagen/hyaluronic acid scaffold modified by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide cross-linking [J] Biomaterials 2002, 23(4):1205-1212.
11. V. Karageorgiou and D. Kaplan Porosity of 3D biornaterial scaffolds and osteogenesis [J] Biomaterials 2005,26(27):5474-5491.
12. N. C. Braier and R. A. Jishi Density functional studies of Cu2+ and Ni2+ binding to chitosan [J] Journal of Molecular Structure-Theochem 2000,499(51-55.
13. A. Slovikova, L. Vojtova and J. Jancar Preparation and modification of collagen-based porous scaffold for tissue engineering [J] Chemical Papers 2008,62(4): 417-422.
14. S. Miot, T. Woodfield, A. U. Daniels, R. Suetterlin, I. Peterschmitt, M. Heberer, C. A. van Blitterswijk, J. Riesle and I. Martin Effects of scaffold composition and architecture on human nasal chondrocyte redifferentiation and cartilaginous matrix deposition [J] Biomaterials 2005,26(15):2479-2489.
15. P. B. Olivia Felt, Robert Gurny Chitosan:A Unique Polysaccharide for Drug Delivery [J] Drug Development and Industrial Pharmacy 1998, Vol.24(No.11): Pages 979-993.
16. S. M. Kuo, S. J. Chang, G. C. C. Niu, C. W. Lan, W. T. Cheng and C. Z. Yang Guided Tissue Regeneration with Use of beta-TCP/Chitosan Composite Membrane [J] Journal of Applied Polymer Science 2009,112(5):3127-3134.
17. R. Kormey, N. Peppas and R. Gumy Mechanisms of solute release from prous hydrophilic polymer [J] International Journal of Pharmaceutics 1983,15(1):25.
18. W. W. Thein-Han, J. Saikhun, C. Pholpramoo, R. D. K. Misra and Y. Kitiyanant Chitosan-gelatin scaffolds for tissue engineering:Physico-chemical properties and biological response of buffalo embryonic stem cells and transfectant of GFP-buffalo embryonic stem cells [J] Acta Biomaterialia 2009,5(9):3453-3466.
19. M. Takechi, Y. Miyamoto, Y. Momota, T. Yuasa, S. Tatehara, M. Nagayama, K. Ishikawa and K. Suzuki The in vitro antibiotic release from anti-washout apatite cement using chitosan [J] Journal of Material Science and Material Medicine 2002, 13(973-978.
20. M. Zilberman and J. J. Elsner Antibiotic-eluting medical devices for various applications [J] Journal of Controlled Release 2008,130(3):202-215.
21. L. S. Nair and C. T. Laurencin Biodegradable polymers as biomaterials [J] Progress in Polymer Science 32(8-9):762-798.
22. Q. Zou, Y. B. Li, L. Zhang, Y. Zuo, J. F. Li and J. D. Li Antibiotic delivery system using nano-hydroxyapatite/chitosan bone cement consisting of berberine [J] Journal of Biomedical Materials Research Part A 2009,89A(4):1108-1117.
1. May, J.W., et al., Clinical classification of post-traumatic tibial osteomyelitis. Journal of Bone and Joint Surgery-American Volume,1989.71A(9):p.1422-1428.
2. He, Y., et al., Effect of antibiotics on the properties of poly(methylmethacrylate)-based bone cement. Journal of Biomedical Materials Research,2002.63(6):p.800-806.
3. Mader, J.T., et al., Antimicrobial treatment of chronic osteomyelitis. Clinical Orthopaedics and Related Research,1999(360):p.47-65.
4. Nikkola, L., P. Viitanen, and N. Ashammakhi, Temporal Control of Drug Release From Biodegradable Polymer:Multicomponent Diclofenac Sodium Releasing PLGA 80/20 Rod. Journal of Biomedical Materials Research Part B-Applied Biomaterials, 2009.89B(2):p.518-526.
5. Schnieders, J., et al., Controlled release of gentamicin from calcium phosphate-poly(lactic acid-co-glycolic acid) composite bone cement. Biomaterials,2006.27(23): p.4239-4249.
6. Walenkamp, G., Self-mixed antibiotic bone cement:western countries learn from developing countries. Acta Orthopaedica,2009.80(5):p.505-507.
7. Meng, Z.X., et al., Fabrication, characterization and in vitro drug release behavior of electrospun PLGA/chitosan nanofibrous scaffold. Materials Chemistry and Physics,2011.125(3):p.606-611.
8. Neut, D., et al., The effect of mixing on gentamicin release from polymethylmethacrylate bone cements. Acta Orthopaedica Scandinavica,2003.74(6): p.670-676.
9. Rasyid, H.N., et al., Concepts for increasing gentamicin release from handmade bone cement beads. Acta Orthopaedica,2009.80(5):p.508-513.
10. De, P., et al., Structure-release rate correlation in collagen gels containing fluorescent drug analogs. Biomaterials,2005.26:p.7164-72.
11. Langer, R., Invited review:polymeric delivery systems for controlled drug release. Chemical Engineering Comminication,1980.6.
12. Parsons, B. and E. Strauss, Surgical management of chronic osteomyelitis. American Journal of Surgery,2004.188(1A):p.57S-66S.
13. Shirtliff, M.E., J.H. Calhoun, and J.T. Mader, Experimental osteomyelitis treatment with antibiotic-impregnated hydroxyapatite. Clinical Orthopaedics and Related Research,2002(401):p.239-247.
14. Javed, S. and K. Kohli, Local Delivery of Minocycline Hydrochloride:A Therapeutic Paradigm in Periodontal Diseases. Current Drug Delivery,2010.7(5):p. 398-406.
15. McLaren, A.C., Alternative materials to acrylic bone cement for delivery of depot antibiotics in orthopaedic infections. Clinical Orthopaedics and Related Research, 2004(427):p.101-106.
16. Thein-Han, W.W., et al., Chitosan-gelatin scaffolds for tissue engineering: Physico-chemical properties and biological response of buffalo embryonic stem cells and transfectant of GFP-buffalo embryonic stem cells. Acta Biomaterialia,2009.5(9): p.3453-3466.
17. Sevy, J.O., et al., Assay method for polymer-controlled antibiotic release from allograft bone to target orthopaedic infections-biomed 2010. Biomed Sci Instrum, 2010.46:p.136-41.
18. Prabu, P., et al., Preparation and drug release activity of scaffolds containing collagen and poly(caprolactone). Journal of Biomedical Materials Research Part A, 2006.79A(1):p.153-158.
19. Roseman, T. and W. Higuchi, Release of medroxyprogesterone acetate from a silicone polymer. Journal of Pharmaceutical Science,1970.59:p.353-357.
20. Chandrasekaran, S. and D. Paul, Dissolution-controlled transport from dispersed matrixes. Journal of Pharmaceutical Science,1982.71(12):p.1339-1402.
21. Peppas, N., ed. Athematical modeling of diffusion process in drug delivery polymeric systems. Controlled Drug Bioavailability ed. V. Smolen and L. Ball. Vol.1. 1984, John Wiley and Sons:New York.203-237.
22. Verguaud, J., ed. Controlled Drug Release of Oral Dosage Forms.1993, Ellis Horwood:New York.21-390.
23. Narasimhan, B. and N. Peppas, eds. The role of modeling studies in the development of future controlled-release devices. Controlled Drug Delivery, ed. K. Park.1997, ACS:Washington, DC.529-555.
24.高秋明and刘兴炎,慢性骨髓炎的治疗.中国矫形外科杂志,2002.10(11)：p.1120-1121.
25. Mackey, D., A. Varlet, and D. Debeaumont, Antibiotic loaded plaster of Paris pellets:an in vitro study of a possible method of local antibiotic therapy in bone infection. Clinical Orthopaedics,1982((167):p.263-8.
26. Mcnally, M., J. Small, and H.e.a. Tofighi, Two-stage management of chronic osteomyelitis of the long bones. Journal of Bone and Joint Surgery,1993.75:p.375-380.
27. Chan, Y., W. Ueng, and C. Wang, Management of small infected tibial defects with antibiotic-impregnated autogenic cancellous bone grafting. Journal of traumatology,1998,45(4):p.758-764.
1. J. W. May, J. B. Jupiter, A. J. Weiland and H. S. Byrd, Clinical classification of post-traumatic tibial osteomyelitis. [J] Journal of Bone and Joint Surgery-American Volume 1989,71A(9):1422-1428.
2. M. Wilson, K. Kelley and T. Thornhill, Infection as a complication of total kneereplacement arthroplasty. Risk factors and treatment in sixty-seven cases.. [J] Journal of Bone and Joint Surgery Am 1990,72(6):878-883.
3. E. Salvati, R. Robinson and S. Zeno, et al., Infection rates after 3175 hip and total knee replacements performed with and without a horizontal unidirectional filtered air-flow system. [J] Journal of Bone and Joint Surgery Am 1982,64(4): 525-535.
4. A. Hanssen and J. Rand, Evaluation and treatment of infection at the site of a total hip or knee arthroplasty. [J] Instrument Course Lecture 1999,48(111-122.
5. R. J. Fitzgerald, Total hip arthroplasty sepsis. Prevention and diagnosis. [J] Orthopaedic Clinics of North America 1992,23(2):259-264.
6. P. J. Wilson, H. Amstutz and A. Czerniecki, et al., Total hip replacement with fixation by acrylic cement. A preliminary study of 100 consecutive McKee-Farrar prosthetic replacements. [J] Journal of Bone and Joint Surgery Am 1972,54(2): 207-236.
7. D. G. Barrett and M. N. Yousaf, Design and Applications of Biodegradable Polyester Tissue Scaffolds Based on Endogenous Monomers Found in Human Metabolism. [J] Molecules 2009,14(10):4022-4050.
8. F. Couet, N. Rajan and D. Mantovani, Macromolecular biomaterials for scaffold-based vascular tissue engineering. [J] Macromolecular Bioscience 2007,7(5): 701-718.
9. E. Witso, L. Persen, P. Benum and K. Bergh, Cortical allograft as a vehicle for antibiotic delivery. [J] Acta Orthopaedica 2005,76(4):481-486.
10. L. Meinel, R. Fajardo, S. Hofmann, R. Langer, J. Chen, B. Snyder, G. Vunjak-Novakovic and D. Kaplan, Silk implants for the healing of critical size bone defects. [J] Bone 2005,37(5):688-698.
11. J. H. Yeo, K. G. Lee, Y. W. Lee and S. Y. Kim, Simple preparation and characteristics of silk fibroin microsphere. [J] European Polymer Journal 2003,39(6): 1195-1199.
12. Y. Yang, F. Ding, H. Wu, W. Hu, W. Liu, H. Liu and X. Gu, Development and evaluation of silk fibroin-based nerve grafts used for peripheral nerve regeneration. [J] Biomaterials 2007,28(36):5526-5535.
13. Y. Morita, N. Tomita, H. Aoki, M. Sonobe, S. Wakitani, Y. Tamada, T. Suguro and K. Ikeuchi, Frictional properties of regenerated cartilage in vitro. [J] Journal of Biomechanics 2006,39(1):103-109.
14. M. Chevillard, P. Couble and J. C. Prudhomme, COMPLETE NUCLEOTIDE-SEQUENCE OF THE GENE ENCODING THE BOMBYX-MORISILK PROTEIN-P25 AND PREDICTED AMINO-ACID-SEQUENCE OF THEPROTEIN. [J] Nucleic Acids Research 1986,14(15):6341-6342.
15. K. Tanaka, N. Kajiyama, K. Ishikura, S. Waga, A. Kikuchi, K. Ohtomo, T. Takagi and S. Mizuno, Determination of the site of disulfide linkage between heavy and light chains of silk fibroin produced by Bombix mori. [J] Biochimica Et Biophysica Acta-Protein Structure and Molecular Enzymology 1999,1432(1):92-103.
16. C. Z. Zhou, F. Confalonieri, M. Jacquet, R. Perasso, Z. G. Li and J. Janin, Silk fibroin:Structural implications of a remarkable amino acid sequence. [J] Proteins-Structure Function and Genetics 2001,44(2):119-122.
17.熊思勇,李明忠,用丝素水溶液制备三维生物材料支架.[J]国外丝绸2009,5：1-4.
18. E. M. Pritchard, T. Valentin, D. Boison and D. L. Kaplan, Incorporation of proteinase inhibitors into silk-based delivery devices for enhanced control of degradation and drug release. [J] Biomaterials 2011,32(3):909-918.
19. V. Karageorgiou and D. Kaplan, Porosity of 3D biornaterial scaffolds and osteogenesis. [J] Biomaterials 2005,26(27):5474-5491.
20.曹正兵,[J]复旦大学博士学位论文2005.
1. Krasko, M.Y., et al., Gentamicin extended release from an injectable polymeric implant. Journal of Controlled Release,2007.117(1):p.90-96.
2. Schnieders, J., et al., Controlled release of gentamicin from calcium phosphate-poly(lactic acid-co-glycolic acid) composite bone cement. Biomaterials,2006.27(23): p.4239-4249.
3. Hendricks, K.J., et al., Elution characteristics of tobramycin from polycaprolactone in a rabbit model. Clinical Orthopaedics and Related Research, 2001(392):p.418-426.
4. Foster, L.J.R., et al., Chitosan-Vancomysin Composite Biomaterial as a Laser Activated Surgical Adhesive with Regional Antimicrobial Activity. Biomacromolecules, 2010.11(12):p.3563-3570.
5. Sarasam, A., et al., Antibacterial activity of chitosan-based matrices on oral pathogens. Journal of Materials Science:Materials in Medicine,2008.19(3):p. 1083-1090.
6. Bleier, B.S., et al., Antibiotic eluting chitosan glycerophosphate implant in the setting of acute bacterial sinusitis:A rabbit model. American Journal of Rhinology & Allergy,2010.24(2):p.129-132.
7. Draget, K.I., G. SkjakBraek, and O. Smidsrod, Alginate based new materials. International Journal of Biological Macromolecules,1997.21(1-2):p.47-55.
8. Matsuno, T., et al., Preparation of injectable 3D-formed beta-tricalcium phosphate bead/alginate composite for bone tissue engineering. Dental Materials Journal,2008.27(6):p.827-834.
9. Hunt, N.C., et al., Encapsulation of fibroblasts causes accelerated alginate hydrogel degradation. Acta Biomaterialia,2010.6(9):p.3649-3656.
10. Wu, C.T., et al., Bioactive inorganic-materials/alginate composite microspheres with controllable drug-delivery ability. Journal of Biomedical Materials Research Part B-Applied Biomaterials,2010.94B(1):p.32-43.
11. Fu, Y.C., et al., Porous bioceramic bead prepared by calcium phosphate with sodium alginate gel and PE powder. Materials Science & Engineering C-Biomimetic and Supramolecular Systems,2008.28(7):p.1149-1158.
12. Koyama, K., et al., Preparation and in Vitro Evaluation of Chitosan-coated Alginate/Calcium Complex Microparticles Loaded with Fluorescein-labeled Lactoferrin. Yakugaku Zasshi-Journal of the Pharmaceutical Society of Japan,2009. 129(12):p.1507-1514.
13. Spicer, P.P. and A.G. Mikos, Fibrin glue as a drug delivery system. Journal of Controlled Release,2010.148(1):p.49-55.
14. Yang, Y, et al., Development and evaluation of silk fibroin-based nerve grafts used for peripheral nerve regeneration. Biomaterials,2007.28(36):p.5526-5535.
15. Yeo, J.H., et al., Simple preparation and characteristics of silk fibroin microsphere. European Polymer Journal,2003.39(6):p.1195-1199.
16. Meinel, L., et al., Silk implants for the healing of critical size bone defects. Bone, 2005.37(5):p.688-698.
17. Morita, Y, et al., Frictional properties of regenerated cartilage in vitro. Journal of Biomechanics,2006.39(1):p.103-109.
18. Pritchard, E.M., et al., Incorporation of proteinase inhibitors into silk-based delivery devices for enhanced control of degradation and drug release. Biomaterials, 2011.32(3):p.909-918.
19. Witso, E., et al., Cortical allograft as a vehicle for antibiotic delivery. Acta Orthopaedica,2005.76(4):p.481-486.
20. Ueng, S.W.N., et al., Development of a biodegradable alginate carrier system for antibiotics and bone cells. Journal of Orthopaedic Research,2007.25(1):p.62-72.
21. Benghuzzi, H., et al., Targeted sustained delivery of tobramycin at the site of a femoral osteotomy, in Biomedical Sciences Instrumentation, Vol 42, L. Waite, Editor. 2006, Instrument Soc Amer:Research Triangle Park. p.530-535.
22. Galjour, C., et al., Stimulation of fracture healing by continuous delivery of demineralized bone matrix proteins and tobramycin, in Biomedical Sciences Instrumentation, J. Gillette, Editor.2005, Instrument Soc Amer. p.122-127.
23. Makarov, C., et al., Vancomycin release from bioresorbable calcium phosphate-polymer composites with high ceramic volume fractions. Journal of Materials Science,2010.45(23):p.6320-6324.