3-羟基丁酸3-羟基己酸共聚物作为人工睑板替代材料的效果初探
|
摘要
睑板修复是眼睑重建的重要部分。目前的传统治疗手段并不能很好地满足修复需要。因此寻找一种合适的人工睑板替代物成为关键问题。本实验中研究了产自微生物的3-羟基丁酸3-羟基己酸共聚物(PHBHHx)作为人工睑板替代材料的应用潜能。将PHBHHx支架置入Sprague-Dawley大鼠的睑板缺损部位,并在术后第1、2、4、8周分别收集实验组、对照组和空白组大鼠的术眼眼睑进行组织学检测鉴定。对PHBHHx支架和ADM的植入效果以及空白组的术后情况进行比较。结果表明,尽管PHBHHx材料植入后的最初两周内呈现出较明显的炎症反应,但较之空白组,实验组的PHBHHx支架和对照组的ADM材料均表现出较好的修复效果。此外,在实验组中还可以观察到PHBHHx植入部位出现了胶原包裹;同时,支架也出现了降解现象。由于PHBHHx材料综合了由软至刚的可控性能,又具有组织相容性和生物可降解性,因此可能成为人工睑板修复材料的较合适选择。
Tarsal repair is an important part for eyelid reconstruction. Presently traditional clinic treatments do not produce satisfactory repair effects. The key is to find a proper artificial tarsal repair material. Microbial poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) was studied for application as artificial tarsal substitute in this study. PHBHHx scaffolds were implanted into tarsal defects of Sprague-Dawley rats. Eyelid samples of implanted materials and blank defect controls were collected for histological examination at weekly intervals post surgery. Results were compared among PHBHHx scaffolds, commercial acellular dermal matrices (ADM) and blank defect controls. Both PHBHHx scaffolds and ADM provided satisfactory repair results compared with the blank controls even though the implanted PHBHHx scaffolds showed a two weeks inflammation. Fibrous encapsulation and scaffold degradation were observed for the PHBHHx implants. Combined with its strong, soft mechanical properties, the tissue compatible and biodegradable PHBHHx was proven to be a suitable candidate for artificial tarsal repair.
Tarsal repair is an important part for eyelid reconstruction. Presently traditional clinic treatments do not produce satisfactory repair effects. The key is to find a proper artificial tarsal repair material. Microbial poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) was studied for application as artificial tarsal substitute in this study. PHBHHx scaffolds were implanted into tarsal defects of Sprague-Dawley rats. Eyelid samples of implanted materials and blank defect controls were collected for histological examination at weekly intervals post surgery. Results were compared among PHBHHx scaffolds, commercial acellular dermal matrices (ADM) and blank defect controls. Both PHBHHx scaffolds and ADM provided satisfactory repair results compared with the blank controls even though the implanted PHBHHx scaffolds showed a two weeks inflammation. Fibrous encapsulation and scaffold degradation were observed for the PHBHHx implants. Combined with its strong, soft mechanical properties, the tissue compatible and biodegradable PHBHHx was proven to be a suitable candidate for artificial tarsal repair.
引文
[1] Brandl H, Gross RA, Lenz RW, Fuller RC. Plastics form bacteria and for bacteria: poly (β-hydroxyalkanoates) as natural, biocompatible, and biodegradable polyesters. In: Fischer A, editor. Advances in Biochemical Engineering/Biotechnology. Berlin, Heidelberg: Springer-Verlag, 1990; p. 77-93.
[2] Vert M, Lenz RW. Preparation and properties of poly-β-malic acid: functional polyester of potential biomedical importance. Polym Preprints (Am Chem Soc, Div Polym Chem) 1979;20:608-11
[3] Wang J G, Bakken LR. Screening of soil bacteria for polyhydroxybutyric acid production and its role in the survival of statvation. Microbiol Ecol 1998;35:94-101.
[4] Madison LL, Huisman GW. Metabolic engineering of poly(3-hydroxyalkanoates): from DNA to plastic. Microbiol Mol Biol Rev 1999;63:21-53.
[5] Lageveen RG, Huisman GW, Preusting H, Ketelaar P, Eggink G, Witholt B. Formation of polyesters by Pseudomonas oleovorans: effect of substrates on formation and composition of poly-(R)-3-hydroxyalkanoates and poly-(R)-3-hydroxyalkanoates. Appl Environ Microbiol 1988;54:2924-32.
[6] Brandl H, Gross RA, Lenz RW, Fuller RC. Pseudomonas oleovorans as a source of poly (β-hydroxyalkanoates) for potential applications as biodegradable polyesters. Appl Environ Microbiol 1988;54:1977-82.
[7] Fritsche K, Lenz RW, Fuller RC. Bacterial polyesters containing branched poly (β-hydroxyalkanoates) units. Int J Biol Macromol 1990;12:92-101.
[8] He W, Tian W, Zhang G, Chen GQ, Zhang Z. Production of novel polyhydroxyalkanoates by Pseudomonas stutzeri 1317 from glucose and soybean oil. FEMS Microbiol Lett 1998;169:45-9.
[9] Lee SY. Bacterial polyhydroxyalkanoates. Biotechnol Bioeng 1996;49:1-14.
[10] Curley JM, Hazer B, Lenz RW, Fuller RC. Production of polyhydroxyalkanoates containing aromic substituents by Pseudomonas oleovorans. Macromolecules 1996;29:1762-6.
[11] Lee SY. Bacterial ployhydroxyalkanoates. Biotechnol Bioeng 1996;49:1-14.
[12] Huijberts GM, Eggink G, Waard PD, Huisman GW, Witholt B. Peudomonas putida KT2442 cultivated on glucose accumulate poly(3-hydroxyalkanoates) consisting of saturated and unsaturated monomers. Appl Environ Microbiol 1992;58:536-44.
[13] Lageveen RG, Huisman GW, Preusting H, Ketelaar P, Eggink G, Witholt B. Formation of polyesters by pseudomonas deovorans: Effect of substrates on formation and composition of poly-(R)-3-hydroxyalkanoates and poly-(R)-3-hydroxyalkanoates. Appl Environ Microbiol 1988;54:2924-32.
[14] Fritzsche K, Lenz RW, Fuller RC. Bacterial polyesters containing branched poly-(β-hydroxyalkanoate) units. Intl J Biol Macromol 1990;12:85-91.
[15] Kim DY, Kim YB, Rhee YH. Bacterial poly (3-hydroxyalkanoates) bearing carbon-carbon triple bonds. Macromolecules 1998;31:4760-3.
[16] Doi Y, Abe C. Biosynthesis and characterization of a new bacterial coployester of 3-hydroxyalkanoates and 3-hydroxy-ω-chloroalkanoates. Macromolecules 1990;23:2705-3707.
[17] Abe H, Doi Y, Fukui T, Eya H. Biosynthesis from gluconate of a random copolyester consisting of 3-hydroxybutyrate and medium-chain-length 3-hydroxyalkanoates by Pseudomonas SP.61-3. Int J Biol Macromol 1994;16:115-9.
[18] Lara LM, Gjalt WH. Metabolic engineering of poly (3-hydroxyalkanoates): from DNA to plastic. MICROBIOL MOL BIOL R 1999;3:21-53.
[19] Steinbuchel A. Polyhydroxyalkanoic acids, In: Novel biomaterials from biological sources.Byrom D (Ed), MacMillan. New York 1991; p. 21-53.
[20] Eggink G, Waard P, Huijberts GN M. Formation of novel poly (hydroxyalkanoates) from long-chain fatty acids. Can J Microbiol 1995;41(Suppl. 1):14-21.
[21] Kim O, Gross RA, Rutherford DR. Bioengineering of poly (β-hydroxyalkanoates) for advanced material applications: incorporation of cyano and nitrophenoxy side chain substituents. Can J Microbiol 1995;41 (Suppl. 1):32-43.
[22] He WN, Tian WD, Zhang G, Chen GQ, Zhang Z. Production of novel polyhydroxy-alkanoates by Pseudomonas stutzeri 1317 from glucose and soybean oil. FEMS Microbiol Lett 1998;169:45-9.
[23] Song JJ, Toon SC. Biosynthesis of novel aromatic copolyesters from insoluble 11-phenoxyundecanoic acid by Pseudomonas putida BM01. Appl Environ Microbiol 1996;62: 536-44.
[24] Kim YB, Rhee YH, Han SH, Heo GS, Kim JS.Poly-3-hydroxyalkanoates produced from Pseudomonas oleovorans grown withω-phenoxyalkanoates. Macromolecules 1996;29:3432-5.
[25] Furukawa T, Matsusue Y, Yasunaga T, Shikinami Y, Okuno M, Nakamura T. Biodegradation behavior of ultra-high-strengenth hydroxyapatite/poly (L-lactide) composite rods for internal fixation of bone fractures. Biomaterials 2000;21:1921-7.
[26] Kim O, Gross RA, Hammar WJ, et al. Microbial synthesis of poly (3-hydroxyalkanoates) containing fluorinated side-chain substituents. Macromolecules 1996;29:4572-81.
[27] Preusting H, Nijenhuis A, Witholt B. Physical characteristics of poly (3-hydroxyalkanoates) and poly(3-hydroxyalkenoates) produced by Pseudomonas oleovorans grown on aliphatic hydrocarbons. Macromolecules 1990;23:4220-4.
[28] Doi Y, Abe C. Biosynthesis and characterization of new bacterial copolyester of 3-hydroxyalkanoates and 3-hydroxy-11-chloroalkanoates. Macromolecules 1990;23:3705-7.
[29] Kunikoa M, NAkamura Y, Doi Y. New bacterial copolysters produced in Alcaligenus eutrophus from organoic acid. Polymer Commun 1988;29:174-6.
[30] Steinbüchel A, Valentin HE. Diversity of bacterial polyhydroxyalkanoic acids. FEMS Microbiol Lett 1995;128:219.
[31] Sudesh K, Abe H, Doi Y. Synthesis, structure and properties of polyhydroxyalkanoates: biological polyesters. Prog Polym Sci 2000;25:1503-55.
[32] Matsumoto K, Matsusaki H, Taguchi S, et al. Cloning and characterization of the Pseudomonas sp. 61-3 phaG Gene involved in polyhydroxyalkanoate biosynthesis. Biomacromolecules 2001;2:142-7.
[33] Matsusaki H, Abe H, Doi Y. Biosynthesis and properties of poly(3- hydroxybutyrate-co-3-hydroxyalkanoates) by recombinant strains of Pseudomonas sp. 61-3, Biomacromolecules 2000;1:17.
[34]胡平,陈国强,张增民,等.生物可降解塑料聚羟基脂肪酸酯的生产及物性表征.合成树脂及塑料1997;14:45-9.
[35] Peter J B, Phil B, Sally J. Organ physical properties of poly (hydroxybutyrate) and copolymers of hydroxybutyrate and hydroxyvalerate. FEMS Microbiol Rev 1992;103:289-98.
[36] Lemoigne M. Products of dehydration and of polymerization of hydroxybutyric acid. Bull Soc Chem Biol 1926;8:770-82.
[37] Zhao W, Chen GQ. Production and characterization of terpolyester poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) by recombinant aeromonas hydrophila 4AK4 harboring genes phaAB. Process Biochem 2007;42:1342-7.
[38] Yan YB, Wu Q, Zhang RQ. Dynamic accumulation and degradation of poly(3-hydroxyalkanoate)s in living cells of Azotobacter vinelandii UWD characterized by 13C NMR. FEMS Microbiol Lett 2000;193:269-73.
[39] Doi Y, Kitamura S, Abe H. Microbial synthesis and characterization of poly (hydroxybutyrate-co-hydroxyhexanoate). Macromolecules 1995;23:4822-8.
[40] Abe H, Kikkawa Y, Aoki H, et al. Crystallization behavior and thermal properties of melt-crystallized poly [(R)-3-hydroxybutyric acid-co-6-hydroxyhexanoic acid]. Int J Biol Macromolecules 1999;25:177-83.
[41] De Koning G. Physical properties of bacterial poly(R)-3-hydroxyalkanoates. Can J Microbiol 1995;41:303-9;
[42] Cross RA, Demello C, Lenz RW. Biosynthesis and characterization of poly (beta-hydroxyalkanoates) produced by Pseudononas oleovorans. Macromolecules 1989;22:1106-15.
[43] Dowes EA, Senior PJ. The role and regulation of energy reserve polymers in microorganisms. Adv Microb Physiol 1973;10:135-266.
[44] Jendrossek D. Microbial degradation of polyesters. Adv Biochem Eng Biotechnol 2001;71:293-325.
[45] Ruiz JA, López NI, Fernández RO, Méndez BS. Polyhydroxyalkanoate degradation is associated with nucleotide accumulation and enhances stress resistance and survival of Pseudomonas oleovorans in natural water microcosms. Appl Environ Microbiol 2001;67:225-30.
[46] Anderson AJ, Dowes EA. Occurense, metabolism, metabolic role, and industrial use of bacterial polyhydroxyalkanoates. Microb Rev 1990;54:450-72.
[47] Emeruwa AC, Hawirko RZ. Poly-β-hydroxybutyrate metabolism during growth and sporulation of clostridium botulinum. J Bacteriol 1973;116:989-93.
[48] Senior PJ, Dawes EA. The regulation of poly-β-hydroxybutyrate metabolism in Azotobacter beijerinckii. Biochem J 1973;34:225.
[49] Alvarez HM, Pucci OH, Steinbüchel A. Lipid storage compounds in marine bacteria. Appl Microbiol Biotechnol 1997;47:132-9.
[50] Reusch RN, Sadoff HL. D-poly-β-hydroxybutyrate in membranes of genetically competent bacteria. J Bacteriol 1983;156:778.
[51] Reusch RN, Hiske TW, Sadoff HL. Poly-β-hydroxybutyrate membrane structure and its relationship to genetic transformability in Escherichia coli. J Bacteriol 1986;168:553-62.
[52] Sudesh K, Abe H, Doi Y. Synthesis, structure and propreties of polyhydroxyalkanoates: biological polyesters. Prog Polym Sci 2000;25:1503-55.
[53] Takehiro M, Fujimoto S,et al. Chronic exposure toβ-hydroxybutyrate inhibits glucose-induced insulin release from pancreatic islets by decreasing NADH contents. Am J Physiol Endocrinol Metab 2005;288:372-80.
[54] Bessman SP, Fishbein WN. Gamma-hydroxybutyrate, a normal brain metabolite. Nature 1963;200:1207-8.
[55] Hunter AS, Long WJ, Ryrie CC. An evaluation of gamma hydroxybutyric acid in paediatric practice. Br J Anaesth 1971;43:620-7.
[56] Gessa GL, Vargiu L, Crabai F, Tagliamonte A, De Montis G. Selective increase of brain dopamine induced by gamma-hydroxybutyrate. Life Sci 1966;5:1921-30.
[57] Gallimberti L, Ferri M, Ferrara SD, Fadda F, Gessa GL. Gamma-hydroxybutyric acid in the treatment of alcohol dependence: a double-blind study. Alcohol Clin Exp Res 1992;16:673-6.
[58] Addolorato G, Balducci G, Capristo E, Attilia ML, Taggi F, Gasbarrini G, Ceccanti M. Gamma-hydroxybutyric acid (GHB) in the treatment of alcohol withdrawal syndrome: a randomized comparative study versus benzodiazepine. Alcohol Clin Exp Res 1999;23:1596-604.
[59] Mamelak M. Gammahydroxybutyrate: an endogenous regulator of energy metabolism. Neurosci Biobehav Rev 1989;13:187-19.
[60] Müller MJ, Paschen U, Seitz HJ. Effect of ketone bodies on glucose production and utilization in the miniature pig. J Clin Invest 1984;74:249-61.
[61] Plecko B, St?ckler IS, Schober E, Mlynárik V, Harrer G, Gruber S, Moser E, M?slinger D, Silgoner H, Ipsiroglu O. Oral ?-hydroxybutyrate supplementation in two patients with hyperinsulinemic hypoglycemia: Monitoring ofβ-hydroxybutyrate levels in blood, CSF and in the brain by in vivo magnetic resonance spectroscopy. Pediatr Res 2002;52,301-6.
[62] Katayama M., Hiraide A, Sugimoto H, Yoshioka T, and Sugimoto T. Effect of ketone bodies on hyperglycemia and lactic acidemia in hemorrhagic stress. J Parenter Enteral Nutr 1994;18:442-6.
[63] HHiraide AH, HKatayama MH, HMizobata YH, HSugimoto HH, HYoshioka TH, HSugimoto TH. Effect of sodium D-3-hydroxybutyrate on amino acidemia in hemorrhagic hypotension. Eur Surg Res 1991;23:250-5.
[64] Zou ZT, Sasaguri S, Rajesh KG., Suzuki R. 3-Hydroxybutyrate administration preventsmyocardial damage after coronary occlusion in rat hearts. Am J Physiol Heart Circ Physiol 2002;283:1968-74.
[65] Mizobata Y, Hiraide A, Katayama M, Sugimoto H, Yoshioka T, Sugimoto T. Oxidation of d(?)3-hydroxybutyrate administered to rats with extensive burns. Surg Today 1996;26:173-8.
[66] Suzuki M, Suzuki M, Sato K, Dohi S, Sato T, Matsuura A, Hiraide A. Effect ofβ-Hydroxybutyrate, a cerebral function improving agent, on Cerebral Hypoxia, Anoxia and Ischemia in Mice and Rats. Jpn J Pharmacol 2001;87:143-50.
[67] Kashiwaya Y, Takeshima T, Mori N, Nakashima K, Clarke K, Veech RL. D-β-Hydroxy-butyrate protects neurons in models of Alzheimer's and Parkinson’s disease. Proc Natl Acad Sci 2000;97:5440-4.
[68] Reger MA,Welsh RK,Watson GS, Cholerton B, Baker LD, Craft S. The Relationship between neuropsychological functioning and driving ability in Dementia: a meta-analysis. Neurobiology of Aging 2004;25:311-4.
[69] Nakamura S, Shibuya M, Saito Y, Nakashima H, Saito F, Higuchi A, Tsubota K. Protective Effect of D-β-Hydroxybutyrate on corneal epithelia in dry eye conditions through suppression of apoptosis. IOVS 2003;44:4682-8.
[70] Scotchfold CA, Cascone MG, et al. HOsteoblast responses to collagen-PVA bioartificial polymers in vitro: the effects of cross-linking method and collagen contentH. Biomaterials1998;19:1-11.
[71] Denuziere A, Ferrier D, Damour O, Domard A. HChitosan–chondroitin sulfate and chitosan–hyaluronate polyelectrolyte complexes: biological propertiesH. Biomaterials 1998;19:1275-85.
[72] Vacanti JP. Looking back and looking ahead. Tissue Engineering 2001;7:107-10.
[73] Caplan AI. Tissue engineering designs for the Future: new logics, old molecules. Tissue Eng 2000;6:1-8.
[74] Langer R, Vacanti JP. Tissue Eng Sci 1993;260:920-6.
[75] Spector M. Novel cell-scaffold interactions encountered in tissue engineering: contractile behavior of musculoskeletal connective tissue cells. Tissue Eng 2002;8:351-7.
[76] Athanasiou KA, Zhu C, Lanctot DR, Agrawal CM, Wang X. Fundamentals of biomechanics in tissue engineering of bone. Tissue Eng 2000;6:361-81
[77] Shin H, Jo S, Mikos AG. Biomimetic materials for tissue engineering. Biomaterials 2003;24:4353-64.
[78]王常勇,袁晓辉,刘爽,等.聚羟基丁酸酯载体人工软骨体内培育的实验研究.中华外科杂志2000;38 :269-71.
[79] Cao Y L, Vacanti JP, Paige KT, Upton J, Vacanti CA. Transplantation of chondrocytes utilizing a polymer-cell contruct to produce tissue engineered cartilage in the shape of a human ear. Plast Reconstr Surg. 1997;100:297-302.
[80]颜炜群,申鸣,杨国书,等.伴刀豆蛋白A及其衍生物对培养软骨细胞蛋白多糖代谢的影响.中国生物化学与分子生物学报1996;6:686-92.
[81]宋业光,马海欢,蔡哲,等.牛透明软骨细胞与组织引导再生胶原膜体外培养后植入体内的研究.中华整形外科杂志1999;15:175-7.
[82]杨志明,项丹,龚全.肌腱组织工程研究.中国现代手术学杂志2000;4:226-8.
[83]张其清,刘玲蓉.医用组织引导再生材料的发展现状基发展方向.中国修复重建外科杂志1997;11:365-7.
[84]姚康德,尹玉姬,成国祥,等.壳聚糖基聚合物的生物医学研究进展.高技术通讯1998;9:55-8.
[85] Xiang Z, Spector M. A glimpse of tissue engineering in China. Tissue Eng 2002;8:169-74.
[86] Liu W, Cui L, Cao Y. A closer view of tissue engineering in China: the experience of tissue construction in immunocompetent animals. Tissue Eng 2003;9:17-30.
[87] Vacanti JP, Langer R. Tissue engineering: the design and fabrication of living replacement devices for surgical reconstruction and transplantation. Lancet 1999:354:32-4.
[88] Nerem RM. Tissue engineering in the USA. Med Biol Eng Comput 1992;30:81.
[89] HHutmacher DW, Sittinger M.H Periosteal cells in bone tissue engineering. Tissue Eng 2003;9 Suppl 1:45-64.
[90] HStrehl R, Schumacher K, de Vries U, Minuth WW.H Proliferating cells versus differentiated cells in tissue engineering. Tissue Eng 2002;8:37-42.
[91] Shin H, Jo S, Mikos AG. Biomimetic materials for tissue engineering. Biomaterials 2003;24:4353-64.
[92] Zinn M, Witholt B, Egli T. Occurrence, synthesis and medical application of bacterial polyhydroxyalkanoates. Adv Drug Delivery Rev 2001;53:5-21.
[93] Williams SF, Martin DP, Horowitz DH. PHA applications: addressing the price performance issue I. Tissue engineering. Int J Biol Macromol 1999;25:111-21.
[94] Reusch RN. Low molecular weight complexed poly(3-hydroxybutyrate): a dynamic and versatile molecule in vivo, Can J Microbiol 41 (Suppl. 1) 1995;50-4.
[95] Sun J, Dai ZW, Zhao Y, Chen GQ. In vitro effect of oligo-hydroxyalkanoates on the growth of mouse fibroblast cell line L929. Biomaterials 2007;28:3896-903.
[96] Martin DP, Peoples OP, Williams SF, Zhong LH. Nutritional and therapeutic uses of 3-hydroxyalkanoate oligomers. US Patent Appl 359086, 1999.
[97] Miller ND, Williams DF. On the biodegradation of poly beta-hydroxybutyrate homopolymer and poly beta-hydroxybutyrate-hydroxyvalerate copolymers. Biomaterials 1987;8:129-37.
[98] Freier T, Kunze G, Nischan C, Kramer S, Sternberg K, SaX M, Hopt UT, Schmitz KP. In vitro and in vivo degradation studies for development of a biodegradable patch based on poly(3-hydroxybutyrate). Biomaterials 2002;23:2649-57.
[99] Wang YW, Mo WK, Yao HL, Wu Q, Chen JC, Chen GQ. Biodegradation studies of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate). Polym Degrad Stabil 2004;85:815–21.
[100] Qu XH, Wu Q, Zhang KY, Chen GQ. In vivo studies of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) based materials: biodegradation and tissue reactions. Biomaterials 2006;27:3540-8.
[101] Williams SF, Martin DP, Horowitz DM, Peoples OP. PHA applications: addressing the price performance issue I. Tissue engineering. Int J Biol Macromol 1999;25:111–21.
[102] Singh S, Maxwell D. Tools of the trade. Best Prac Res Clin Obst Gyn 2006;20:41-59.
[103] Shishatskaya EI, Volova TG, Puzyr AP, Mogilnaya OA, Efremov SN. Tissue response to the implantation of biodegradable polyhydroxyalkanoate sutures. J Mater Sci-Mater M 2004;15: 719-28.
[104] Volova T, Shishatskaya E, Sevastianov V, Efremov S, Mogilnaya O. Results of biomedical investigations of PHB and PHB/PHV fibers. Biochem Eng J 2003;16:125-33.
[105] Baptist JN, Ziegler JB. Method of making absorbable surgical sutures from poly beta hydroxyacids. US Patent No: 3225766, 1965.
[106] Shishatskaya EI, Volova TG, Puzyr AP, Mogilnaya OA and Efremov SN: Tissue response to the implantation of biodegradable polyhydroxyalkanoate sutures. J Mater Sci Mater Med 2004;15:719-28.
[107] Misra SK, Valappil SP, Roy I, Boccaccini AR. Polyhydroxyalkanoate (PHA)/inorganic phase composites for tissue engineering applications. Biomacromolecules 2006;7:2249-58.
[108] Ni J, Wang M. In vitro evaluation of hydroxyapatite reinforced polyhydroxybutyrate composite. Mater Sci Eng C-Bio S 2002;20:101-9.
[109] Luklinska ZB, Bonfield W. Morphology and ultrastructure of the interface between hydroxyapatite-polyhydroxybutyrate composite implant and bone. J Mater Sci-Mater M 1997;8:379-83.
[110] Chen LJ, Wang M. Production and evaluation of biodegradable composites based on PHB-PHV copolymer. Biomaterials 2002;23:2631-9.
[111] K?se GT, Korkusuz F, Korkusuz P, Hasirci V. In vivo tissue engineering of bone using poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) and collagen scaffolds. Tissue Eng2004;10:1234-50.
[112] Wang YW, Wu QO, Chen GQ. Attachment, proliferation and differentiation of osteoblasts on random biopolyester poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) scaffolds. Biomaterials 2004;25:669-75.
[113] Wang YW, Wu Q, Chen JC, Chen GQ. Evaluation of threedimensional scaffolds made of blends of hydroxyapatite and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) for bone reconstruction. Biomaterials 2005;26:899-904.
[114] Yang M, Zhu SS, Chen Y, Chang ZJ, Chen GQ, Gong YD, Zhao NM, Zhang XF. Studies on bone marrow stromal cells affinity of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate). Biomaterials 2004; 25:1365-73.
[115] Hu YJ, Wei X, Zhao W, Liu YS, Chen GQ. Biocompatibility of poly(3- hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) with bone marrow mesenchymal stem cells. Acta Biomater 2008;5:1115-25.
[116] L?bler M, SaX M, Schmitz KP, Hopt UT. Biomaterial implants induce the inflammation marker CRP at the site of implantation. J Biomed Mater Res 2003;61:165-7.
[117] Behrend D, Nischan C, Kunze C, Sass M, Schmitz KP. Resorbable sacffold for tissue engineering. Med. Biol. Eng. Comput. 1999;37:1510-1.
[118] Fukuda S, Sakai N, Kamata SE, Nameki H, Kishimoto S, Nishikawa N, Kaneko S, Miyata M, Fujii M, Inuyama Y. Surgical results of skull base surgery for the treatment of head and neck malignancies involving skull base: multi-institutional studies on 143 cases in Japan. Auris Nasus Larynx 2001;28:S71-5.
[119] Bowald SF, Johansson EG. A novel surgical materials. Eurpean Patent No. 0349 505 A2, 1990.
[120] Janousek P, Kabelka Z, Rygl M, Lesny P, Grabec P, Fajstavr J, Jurovcík M, Snajdauf J. Corrosive injury of the oesophagus in children. Int J Ped Otorhinol 2006;70:1103-7.
[121] Williams SF, Martin DP. Application of PHAs in Medicine and Pharmacy. In: Doi Y, Steinbüchel A, editors. Biopolymers, vol. 10. Weinheim: Wiley-VCH; 2002, p. 91-121.
[122] Opitz F, Schenke-Layland K, Richter W, Martin DP, Degenkolbe I, Wahlers T, StockUA. Tissue engineering of ovine aortic blood vessel substitutes using applied shear stress and enzymatically derived vascular smooth muscle cells. Ann Biomed Eng 2004;32:212-22.
[123] Opitz F, Schenke-Layland K, Cohnert TU, Starcher B, Halbhuber KJ, Martin DP, StockUA. Tissue engineering of aortic tissue: dire consequence of suboptimal elastic fiber synthesis in vivo. Cardiovasc Res 2004;63:719-30.
[124] Qu XH, Wu Q, Liang J, Qu X, Wang SG, Chen GQ. Enhanced vascular-related cellular affinity on surface modified copolyesters of 3-hydroxybutyrate and 3-hydroxyhexanoate (PHBHHx). Biomaterials 2005;26:6991-7001.
[125] Qu XH, Wu Q, Zhang KY, Chen GQ. In vivo studies of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) based materials: biodegradation and tissue reactions. Biomaterials 2006;27:3540-8.
[126] Qu XH, Wu Q, Liang J, Zou B, Chen GQ. Effect of 3-hydroxyhexanoate content in poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) on in vitro growth and differentiation of smooth muscle cells. Biomaterials 2006;27:2944-50.
[127] Qu XH, Wu Q, Chen GQ. In vitro study on hemocompatibility and cytocompatibility of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate). J Biomater Sci Polym Ed 2006;17:1107-21.
[128] Sodian R, Hoerstrup SP, Sperling JS, Daebritz S, Martin DP, Moran AM, Kim BS, Schoen FJ, Vacanti JP, Mayer JE. Early in vivo experience with tissue-engineered trileaflet heart valves. Circulation 2000;102(Suppl.):22-9.
[129] Martin DP, Williams SF. Medical applications of poly 4-hydroxybutyrate: a strong flexible absorbable biomaterial. Biochem Eng J 2003;16:97-105.
[130] Sodian R, Loebe M, Hein A, Martin DP, Hoerstrup SP, Potapov EV, Hausmann H, Lueth T, Hetzer R. Application of stereolithography for scaffold fabrication for tissue engineered heart valves. ASAIO J 2002;48:12-6.
[131] Hazari A, Johansson-Rudén G, Junemo-Bostrom K, Ljungberg C, Terenghi G, Green C, Wiberg M. A new resorbable wrap around implant as an alternative nerve repair technique. J Hand Surg 1999;24:291-5.
[132] Ljungberg C, Johansson RG, Bostrom KJ, Novikov L, Weiberg M. Neuronal survival using a resorbable synthetic conduit as an alternative to primary nerve repair. Microsurgery 1999;19:250-64.
[133] Hazari A, Wiberg M, Johansson RG, Green C, Terenghi G. A resorbable nerve conduit as an alternative to nerve autograft in nerve gap repair. Br J Plast Surg 1999;52:653-7.
[134] Mosahebi A, Fuller P, Wiberg M, Terenghi G. Effect of allogeneic schwann cell transplantation on peripheral nerve regeneration. Exp Neurol 2002;173:213-23.
[135] Li J, Li L, Ren BC. Experimental study of the eyelid reconstruction in situ with the acellular xenogeneic dermal matrix. Chin J Plast Surg 2007;23:170-4.
[136]侯忠敏,荣运久.眼科基础与临床问答.北京:人民军医出版社; 1998. p. 9-10.
[137]杨安峰,王平.大鼠的解剖和组织.北京:科学出版社; 1985. p. 34.
[138] Goldberg RA, Joshi AR, McCann JD, Shorr N. Management of severe cicatricial entropion using shared mucosal grafts. Arch Ophthalmol 1999;117:1255-9.
[139] Chen JQ, Gu JJ, Peng HJ, Huang T, Chen LS, et al. The eyelid reconstruction in situ with allograft acellular dermal matrix. Chin J Ophthalmol 2005;41:409-13.
[140] Mannor GE, Mathers WD, Wolfley DE, Martinez JA. Hard-palate mucosa graft in Stevens-Johnson syndrome. Am J Ophthalmol 1994;118:786-91
[141] Wójcicki P, Kobus K. Treatment of entropion using mucous membrane and cartilage graftsfrom the nasal septum. Klin Oczna 2006;108:431-3.
[142] Tenzel RR, Miller GR, Rubenzik R. Cicatricial upper lid entropion: treated with banked scleral graft. Arch Ophthalmol 1975;93:999-1000.
[143] Ren BC, Zhao JQ, Zhang J. Experimental study on eyelid reconstruction with acellular xenogenic dermal matrix. Chin J Ophthalmol 2007;43:906-11.
[144] Sabate FN, Buesseler JA, Krosney NM, Yamashita T. Experimental and clinical studies of glycerin preserved scleral homografts. Eye Ear Nose Throat Monthly 1967;46:1162-6.
[145] Seiff SR, Chang JS, MH Hurt, Khayam-Bashi H. Polymerase chain reaction identification of human immunodeficiency virus-1 in preserved human sclera. Am J Ophthalmol 1994;118:528-30.
[146] McCord C, Nahai FR, Codner MA, Hester TR. Use of porcine acellular dermal matrix (Enduragen) grafts in eyelids: a review of 69 patients and 129 eyelids. Plast Reconstr Surg 2008;122:1206-13.
[147] Aragona F. Is bovine collagen safe? J Urol 1991;97:279-81.
[148] Srivastava A, Jennings LJ, Hanumadass M, Sethi S, DeSagun E, Pavlis N, Reyes H, Walter RJ. Xenogeneic acellular dermal matrix as a dermal substitute in rats. J Burn Care Res 1999;20:382-90.
[149] Clark G. Staining procedures. Baltimore: Williams and Wilkins; 1973, p. 33-5.
[150] Cheng ST, Chen ZF, Chen GQ. The expression of cross-linked elastin by rabbit blood vessel smooth muscle cells cultured in polyhydroxyalkanoate scaffolds. Biomaterials 2008;29:4187-94.
[151] The Association for Research in Vision and Ophthalmology. Statement for the use of animals in ophthalmic and vision research. In: Animals in Research Committee, editor. Handbook for the use of animals in biomedical research. Bethesda: The Association forResearch in Vision and Ophthalmology; 1993. p. 15-16.
[152] Stocum DL. Regenerative biology and medicine. Oxford: Elsevier Science; 2006. p. 21-36.
[153] Anderson JM. Biological responses to materials. Annu Rev Mater Res 2001;31:81-110.
[154] Jutila MA. Leukocyte traffic to sites of inflammation. APMIS 1992;100:191-201.
[155] Cotran RZ, Kumar V, Robbins SL, editors. Pathologic basis of disease. Philadelphia: Saunders; 1979. p. 50-112.
[156] Williams GT, Williams WJ. Granulomatous inflammation--a review. J Clin Pathol 1983;36:723-33.
[157] Lanza RP, Langer R, Chick WL. Principles of tissue engineering. Austin: Academic Press; 1997.
[158] B?stman OM. Absorbable implants for the fixation of fractures. J Bone Joint Surg Am 1991;73:148-53.
[159] Williams SF, Martin DP. Applications of PHAs in medicine and pharmacy. In: Doy I, Steinbuchel A, editors. Biopolymers polyesters III. Weinheim: Wiley-VCH; 2001. p. 91-127.
[160] Rashid ST, Salacinski HJ, Hamilton G, Seifalian AM. The use of animal models in developing the discipline of cardiovascular tissue engineering: a review. Biomaterials 2004;25:1627–37.
[161] Shishatskaya EI, Volova TG, Puzyr AP, Mogilnaya OA, Efremov SN. Tissue response to the implantation of biodegradable polyhydroxyalkanoate sutures. J Mater Sci Mater Med 2004;15:719-28.
[162] Anderson JM. Mechanisms of inflammation and infection with implanted devices. Cardiovasc Pathol 1993;2:33-41.
[163] Anderson JM. Inflammatory response to implants. ASAIO Trans 1988;34:101-7.
[164] Rae T. The macrophage response to implant materials. Crit Rev Biocompatibility 1986;2:97-126.
[165] Chambers TJ, Spector WG. Inflammatory giant cells. Immunobiology 1982;161:283-9.
[166] Anderson JM. Biological responses to materials. Annu Rev Mater Res 2001;31:81-110.
[167] Srivastava A, DeSagun EZ, Jennings LJ, Sethi S, Phuangsab A, Hanumadass M, Reyes HM, Walter RJ. Use of porcine acellular dermal matrix as a dermal substitute in rats. Ann Surg 2001;233:400-8.
[168] Schoen FJ, Mitchell RN. Tissue, the extracellular matrix, and cell-biomaterial interactions. In: Ratner BD, Hoffman AS, Schoen FJ, Lemons JE, editors. Biomaterials science: an introduction to materials in medicine. Singapore: Elsevier science Pte Ltd; 2004. p. 260-81.
[169] Williams DF. On the nature of biomaterials. Biomaterials 2009;30:5897-909.
[2] Vert M, Lenz RW. Preparation and properties of poly-β-malic acid: functional polyester of potential biomedical importance. Polym Preprints (Am Chem Soc, Div Polym Chem) 1979;20:608-11
[3] Wang J G, Bakken LR. Screening of soil bacteria for polyhydroxybutyric acid production and its role in the survival of statvation. Microbiol Ecol 1998;35:94-101.
[4] Madison LL, Huisman GW. Metabolic engineering of poly(3-hydroxyalkanoates): from DNA to plastic. Microbiol Mol Biol Rev 1999;63:21-53.
[5] Lageveen RG, Huisman GW, Preusting H, Ketelaar P, Eggink G, Witholt B. Formation of polyesters by Pseudomonas oleovorans: effect of substrates on formation and composition of poly-(R)-3-hydroxyalkanoates and poly-(R)-3-hydroxyalkanoates. Appl Environ Microbiol 1988;54:2924-32.
[6] Brandl H, Gross RA, Lenz RW, Fuller RC. Pseudomonas oleovorans as a source of poly (β-hydroxyalkanoates) for potential applications as biodegradable polyesters. Appl Environ Microbiol 1988;54:1977-82.
[7] Fritsche K, Lenz RW, Fuller RC. Bacterial polyesters containing branched poly (β-hydroxyalkanoates) units. Int J Biol Macromol 1990;12:92-101.
[8] He W, Tian W, Zhang G, Chen GQ, Zhang Z. Production of novel polyhydroxyalkanoates by Pseudomonas stutzeri 1317 from glucose and soybean oil. FEMS Microbiol Lett 1998;169:45-9.
[9] Lee SY. Bacterial polyhydroxyalkanoates. Biotechnol Bioeng 1996;49:1-14.
[10] Curley JM, Hazer B, Lenz RW, Fuller RC. Production of polyhydroxyalkanoates containing aromic substituents by Pseudomonas oleovorans. Macromolecules 1996;29:1762-6.
[11] Lee SY. Bacterial ployhydroxyalkanoates. Biotechnol Bioeng 1996;49:1-14.
[12] Huijberts GM, Eggink G, Waard PD, Huisman GW, Witholt B. Peudomonas putida KT2442 cultivated on glucose accumulate poly(3-hydroxyalkanoates) consisting of saturated and unsaturated monomers. Appl Environ Microbiol 1992;58:536-44.
[13] Lageveen RG, Huisman GW, Preusting H, Ketelaar P, Eggink G, Witholt B. Formation of polyesters by pseudomonas deovorans: Effect of substrates on formation and composition of poly-(R)-3-hydroxyalkanoates and poly-(R)-3-hydroxyalkanoates. Appl Environ Microbiol 1988;54:2924-32.
[14] Fritzsche K, Lenz RW, Fuller RC. Bacterial polyesters containing branched poly-(β-hydroxyalkanoate) units. Intl J Biol Macromol 1990;12:85-91.
[15] Kim DY, Kim YB, Rhee YH. Bacterial poly (3-hydroxyalkanoates) bearing carbon-carbon triple bonds. Macromolecules 1998;31:4760-3.
[16] Doi Y, Abe C. Biosynthesis and characterization of a new bacterial coployester of 3-hydroxyalkanoates and 3-hydroxy-ω-chloroalkanoates. Macromolecules 1990;23:2705-3707.
[17] Abe H, Doi Y, Fukui T, Eya H. Biosynthesis from gluconate of a random copolyester consisting of 3-hydroxybutyrate and medium-chain-length 3-hydroxyalkanoates by Pseudomonas SP.61-3. Int J Biol Macromol 1994;16:115-9.
[18] Lara LM, Gjalt WH. Metabolic engineering of poly (3-hydroxyalkanoates): from DNA to plastic. MICROBIOL MOL BIOL R 1999;3:21-53.
[19] Steinbuchel A. Polyhydroxyalkanoic acids, In: Novel biomaterials from biological sources.Byrom D (Ed), MacMillan. New York 1991; p. 21-53.
[20] Eggink G, Waard P, Huijberts GN M. Formation of novel poly (hydroxyalkanoates) from long-chain fatty acids. Can J Microbiol 1995;41(Suppl. 1):14-21.
[21] Kim O, Gross RA, Rutherford DR. Bioengineering of poly (β-hydroxyalkanoates) for advanced material applications: incorporation of cyano and nitrophenoxy side chain substituents. Can J Microbiol 1995;41 (Suppl. 1):32-43.
[22] He WN, Tian WD, Zhang G, Chen GQ, Zhang Z. Production of novel polyhydroxy-alkanoates by Pseudomonas stutzeri 1317 from glucose and soybean oil. FEMS Microbiol Lett 1998;169:45-9.
[23] Song JJ, Toon SC. Biosynthesis of novel aromatic copolyesters from insoluble 11-phenoxyundecanoic acid by Pseudomonas putida BM01. Appl Environ Microbiol 1996;62: 536-44.
[24] Kim YB, Rhee YH, Han SH, Heo GS, Kim JS.Poly-3-hydroxyalkanoates produced from Pseudomonas oleovorans grown withω-phenoxyalkanoates. Macromolecules 1996;29:3432-5.
[25] Furukawa T, Matsusue Y, Yasunaga T, Shikinami Y, Okuno M, Nakamura T. Biodegradation behavior of ultra-high-strengenth hydroxyapatite/poly (L-lactide) composite rods for internal fixation of bone fractures. Biomaterials 2000;21:1921-7.
[26] Kim O, Gross RA, Hammar WJ, et al. Microbial synthesis of poly (3-hydroxyalkanoates) containing fluorinated side-chain substituents. Macromolecules 1996;29:4572-81.
[27] Preusting H, Nijenhuis A, Witholt B. Physical characteristics of poly (3-hydroxyalkanoates) and poly(3-hydroxyalkenoates) produced by Pseudomonas oleovorans grown on aliphatic hydrocarbons. Macromolecules 1990;23:4220-4.
[28] Doi Y, Abe C. Biosynthesis and characterization of new bacterial copolyester of 3-hydroxyalkanoates and 3-hydroxy-11-chloroalkanoates. Macromolecules 1990;23:3705-7.
[29] Kunikoa M, NAkamura Y, Doi Y. New bacterial copolysters produced in Alcaligenus eutrophus from organoic acid. Polymer Commun 1988;29:174-6.
[30] Steinbüchel A, Valentin HE. Diversity of bacterial polyhydroxyalkanoic acids. FEMS Microbiol Lett 1995;128:219.
[31] Sudesh K, Abe H, Doi Y. Synthesis, structure and properties of polyhydroxyalkanoates: biological polyesters. Prog Polym Sci 2000;25:1503-55.
[32] Matsumoto K, Matsusaki H, Taguchi S, et al. Cloning and characterization of the Pseudomonas sp. 61-3 phaG Gene involved in polyhydroxyalkanoate biosynthesis. Biomacromolecules 2001;2:142-7.
[33] Matsusaki H, Abe H, Doi Y. Biosynthesis and properties of poly(3- hydroxybutyrate-co-3-hydroxyalkanoates) by recombinant strains of Pseudomonas sp. 61-3, Biomacromolecules 2000;1:17.
[34]胡平,陈国强,张增民,等.生物可降解塑料聚羟基脂肪酸酯的生产及物性表征.合成树脂及塑料1997;14:45-9.
[35] Peter J B, Phil B, Sally J. Organ physical properties of poly (hydroxybutyrate) and copolymers of hydroxybutyrate and hydroxyvalerate. FEMS Microbiol Rev 1992;103:289-98.
[36] Lemoigne M. Products of dehydration and of polymerization of hydroxybutyric acid. Bull Soc Chem Biol 1926;8:770-82.
[37] Zhao W, Chen GQ. Production and characterization of terpolyester poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) by recombinant aeromonas hydrophila 4AK4 harboring genes phaAB. Process Biochem 2007;42:1342-7.
[38] Yan YB, Wu Q, Zhang RQ. Dynamic accumulation and degradation of poly(3-hydroxyalkanoate)s in living cells of Azotobacter vinelandii UWD characterized by 13C NMR. FEMS Microbiol Lett 2000;193:269-73.
[39] Doi Y, Kitamura S, Abe H. Microbial synthesis and characterization of poly (hydroxybutyrate-co-hydroxyhexanoate). Macromolecules 1995;23:4822-8.
[40] Abe H, Kikkawa Y, Aoki H, et al. Crystallization behavior and thermal properties of melt-crystallized poly [(R)-3-hydroxybutyric acid-co-6-hydroxyhexanoic acid]. Int J Biol Macromolecules 1999;25:177-83.
[41] De Koning G. Physical properties of bacterial poly(R)-3-hydroxyalkanoates. Can J Microbiol 1995;41:303-9;
[42] Cross RA, Demello C, Lenz RW. Biosynthesis and characterization of poly (beta-hydroxyalkanoates) produced by Pseudononas oleovorans. Macromolecules 1989;22:1106-15.
[43] Dowes EA, Senior PJ. The role and regulation of energy reserve polymers in microorganisms. Adv Microb Physiol 1973;10:135-266.
[44] Jendrossek D. Microbial degradation of polyesters. Adv Biochem Eng Biotechnol 2001;71:293-325.
[45] Ruiz JA, López NI, Fernández RO, Méndez BS. Polyhydroxyalkanoate degradation is associated with nucleotide accumulation and enhances stress resistance and survival of Pseudomonas oleovorans in natural water microcosms. Appl Environ Microbiol 2001;67:225-30.
[46] Anderson AJ, Dowes EA. Occurense, metabolism, metabolic role, and industrial use of bacterial polyhydroxyalkanoates. Microb Rev 1990;54:450-72.
[47] Emeruwa AC, Hawirko RZ. Poly-β-hydroxybutyrate metabolism during growth and sporulation of clostridium botulinum. J Bacteriol 1973;116:989-93.
[48] Senior PJ, Dawes EA. The regulation of poly-β-hydroxybutyrate metabolism in Azotobacter beijerinckii. Biochem J 1973;34:225.
[49] Alvarez HM, Pucci OH, Steinbüchel A. Lipid storage compounds in marine bacteria. Appl Microbiol Biotechnol 1997;47:132-9.
[50] Reusch RN, Sadoff HL. D-poly-β-hydroxybutyrate in membranes of genetically competent bacteria. J Bacteriol 1983;156:778.
[51] Reusch RN, Hiske TW, Sadoff HL. Poly-β-hydroxybutyrate membrane structure and its relationship to genetic transformability in Escherichia coli. J Bacteriol 1986;168:553-62.
[52] Sudesh K, Abe H, Doi Y. Synthesis, structure and propreties of polyhydroxyalkanoates: biological polyesters. Prog Polym Sci 2000;25:1503-55.
[53] Takehiro M, Fujimoto S,et al. Chronic exposure toβ-hydroxybutyrate inhibits glucose-induced insulin release from pancreatic islets by decreasing NADH contents. Am J Physiol Endocrinol Metab 2005;288:372-80.
[54] Bessman SP, Fishbein WN. Gamma-hydroxybutyrate, a normal brain metabolite. Nature 1963;200:1207-8.
[55] Hunter AS, Long WJ, Ryrie CC. An evaluation of gamma hydroxybutyric acid in paediatric practice. Br J Anaesth 1971;43:620-7.
[56] Gessa GL, Vargiu L, Crabai F, Tagliamonte A, De Montis G. Selective increase of brain dopamine induced by gamma-hydroxybutyrate. Life Sci 1966;5:1921-30.
[57] Gallimberti L, Ferri M, Ferrara SD, Fadda F, Gessa GL. Gamma-hydroxybutyric acid in the treatment of alcohol dependence: a double-blind study. Alcohol Clin Exp Res 1992;16:673-6.
[58] Addolorato G, Balducci G, Capristo E, Attilia ML, Taggi F, Gasbarrini G, Ceccanti M. Gamma-hydroxybutyric acid (GHB) in the treatment of alcohol withdrawal syndrome: a randomized comparative study versus benzodiazepine. Alcohol Clin Exp Res 1999;23:1596-604.
[59] Mamelak M. Gammahydroxybutyrate: an endogenous regulator of energy metabolism. Neurosci Biobehav Rev 1989;13:187-19.
[60] Müller MJ, Paschen U, Seitz HJ. Effect of ketone bodies on glucose production and utilization in the miniature pig. J Clin Invest 1984;74:249-61.
[61] Plecko B, St?ckler IS, Schober E, Mlynárik V, Harrer G, Gruber S, Moser E, M?slinger D, Silgoner H, Ipsiroglu O. Oral ?-hydroxybutyrate supplementation in two patients with hyperinsulinemic hypoglycemia: Monitoring ofβ-hydroxybutyrate levels in blood, CSF and in the brain by in vivo magnetic resonance spectroscopy. Pediatr Res 2002;52,301-6.
[62] Katayama M., Hiraide A, Sugimoto H, Yoshioka T, and Sugimoto T. Effect of ketone bodies on hyperglycemia and lactic acidemia in hemorrhagic stress. J Parenter Enteral Nutr 1994;18:442-6.
[63] HHiraide AH, HKatayama MH, HMizobata YH, HSugimoto HH, HYoshioka TH, HSugimoto TH. Effect of sodium D-3-hydroxybutyrate on amino acidemia in hemorrhagic hypotension. Eur Surg Res 1991;23:250-5.
[64] Zou ZT, Sasaguri S, Rajesh KG., Suzuki R. 3-Hydroxybutyrate administration preventsmyocardial damage after coronary occlusion in rat hearts. Am J Physiol Heart Circ Physiol 2002;283:1968-74.
[65] Mizobata Y, Hiraide A, Katayama M, Sugimoto H, Yoshioka T, Sugimoto T. Oxidation of d(?)3-hydroxybutyrate administered to rats with extensive burns. Surg Today 1996;26:173-8.
[66] Suzuki M, Suzuki M, Sato K, Dohi S, Sato T, Matsuura A, Hiraide A. Effect ofβ-Hydroxybutyrate, a cerebral function improving agent, on Cerebral Hypoxia, Anoxia and Ischemia in Mice and Rats. Jpn J Pharmacol 2001;87:143-50.
[67] Kashiwaya Y, Takeshima T, Mori N, Nakashima K, Clarke K, Veech RL. D-β-Hydroxy-butyrate protects neurons in models of Alzheimer's and Parkinson’s disease. Proc Natl Acad Sci 2000;97:5440-4.
[68] Reger MA,Welsh RK,Watson GS, Cholerton B, Baker LD, Craft S. The Relationship between neuropsychological functioning and driving ability in Dementia: a meta-analysis. Neurobiology of Aging 2004;25:311-4.
[69] Nakamura S, Shibuya M, Saito Y, Nakashima H, Saito F, Higuchi A, Tsubota K. Protective Effect of D-β-Hydroxybutyrate on corneal epithelia in dry eye conditions through suppression of apoptosis. IOVS 2003;44:4682-8.
[70] Scotchfold CA, Cascone MG, et al. HOsteoblast responses to collagen-PVA bioartificial polymers in vitro: the effects of cross-linking method and collagen contentH. Biomaterials1998;19:1-11.
[71] Denuziere A, Ferrier D, Damour O, Domard A. HChitosan–chondroitin sulfate and chitosan–hyaluronate polyelectrolyte complexes: biological propertiesH. Biomaterials 1998;19:1275-85.
[72] Vacanti JP. Looking back and looking ahead. Tissue Engineering 2001;7:107-10.
[73] Caplan AI. Tissue engineering designs for the Future: new logics, old molecules. Tissue Eng 2000;6:1-8.
[74] Langer R, Vacanti JP. Tissue Eng Sci 1993;260:920-6.
[75] Spector M. Novel cell-scaffold interactions encountered in tissue engineering: contractile behavior of musculoskeletal connective tissue cells. Tissue Eng 2002;8:351-7.
[76] Athanasiou KA, Zhu C, Lanctot DR, Agrawal CM, Wang X. Fundamentals of biomechanics in tissue engineering of bone. Tissue Eng 2000;6:361-81
[77] Shin H, Jo S, Mikos AG. Biomimetic materials for tissue engineering. Biomaterials 2003;24:4353-64.
[78]王常勇,袁晓辉,刘爽,等.聚羟基丁酸酯载体人工软骨体内培育的实验研究.中华外科杂志2000;38 :269-71.
[79] Cao Y L, Vacanti JP, Paige KT, Upton J, Vacanti CA. Transplantation of chondrocytes utilizing a polymer-cell contruct to produce tissue engineered cartilage in the shape of a human ear. Plast Reconstr Surg. 1997;100:297-302.
[80]颜炜群,申鸣,杨国书,等.伴刀豆蛋白A及其衍生物对培养软骨细胞蛋白多糖代谢的影响.中国生物化学与分子生物学报1996;6:686-92.
[81]宋业光,马海欢,蔡哲,等.牛透明软骨细胞与组织引导再生胶原膜体外培养后植入体内的研究.中华整形外科杂志1999;15:175-7.
[82]杨志明,项丹,龚全.肌腱组织工程研究.中国现代手术学杂志2000;4:226-8.
[83]张其清,刘玲蓉.医用组织引导再生材料的发展现状基发展方向.中国修复重建外科杂志1997;11:365-7.
[84]姚康德,尹玉姬,成国祥,等.壳聚糖基聚合物的生物医学研究进展.高技术通讯1998;9:55-8.
[85] Xiang Z, Spector M. A glimpse of tissue engineering in China. Tissue Eng 2002;8:169-74.
[86] Liu W, Cui L, Cao Y. A closer view of tissue engineering in China: the experience of tissue construction in immunocompetent animals. Tissue Eng 2003;9:17-30.
[87] Vacanti JP, Langer R. Tissue engineering: the design and fabrication of living replacement devices for surgical reconstruction and transplantation. Lancet 1999:354:32-4.
[88] Nerem RM. Tissue engineering in the USA. Med Biol Eng Comput 1992;30:81.
[89] HHutmacher DW, Sittinger M.H Periosteal cells in bone tissue engineering. Tissue Eng 2003;9 Suppl 1:45-64.
[90] HStrehl R, Schumacher K, de Vries U, Minuth WW.H Proliferating cells versus differentiated cells in tissue engineering. Tissue Eng 2002;8:37-42.
[91] Shin H, Jo S, Mikos AG. Biomimetic materials for tissue engineering. Biomaterials 2003;24:4353-64.
[92] Zinn M, Witholt B, Egli T. Occurrence, synthesis and medical application of bacterial polyhydroxyalkanoates. Adv Drug Delivery Rev 2001;53:5-21.
[93] Williams SF, Martin DP, Horowitz DH. PHA applications: addressing the price performance issue I. Tissue engineering. Int J Biol Macromol 1999;25:111-21.
[94] Reusch RN. Low molecular weight complexed poly(3-hydroxybutyrate): a dynamic and versatile molecule in vivo, Can J Microbiol 41 (Suppl. 1) 1995;50-4.
[95] Sun J, Dai ZW, Zhao Y, Chen GQ. In vitro effect of oligo-hydroxyalkanoates on the growth of mouse fibroblast cell line L929. Biomaterials 2007;28:3896-903.
[96] Martin DP, Peoples OP, Williams SF, Zhong LH. Nutritional and therapeutic uses of 3-hydroxyalkanoate oligomers. US Patent Appl 359086, 1999.
[97] Miller ND, Williams DF. On the biodegradation of poly beta-hydroxybutyrate homopolymer and poly beta-hydroxybutyrate-hydroxyvalerate copolymers. Biomaterials 1987;8:129-37.
[98] Freier T, Kunze G, Nischan C, Kramer S, Sternberg K, SaX M, Hopt UT, Schmitz KP. In vitro and in vivo degradation studies for development of a biodegradable patch based on poly(3-hydroxybutyrate). Biomaterials 2002;23:2649-57.
[99] Wang YW, Mo WK, Yao HL, Wu Q, Chen JC, Chen GQ. Biodegradation studies of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate). Polym Degrad Stabil 2004;85:815–21.
[100] Qu XH, Wu Q, Zhang KY, Chen GQ. In vivo studies of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) based materials: biodegradation and tissue reactions. Biomaterials 2006;27:3540-8.
[101] Williams SF, Martin DP, Horowitz DM, Peoples OP. PHA applications: addressing the price performance issue I. Tissue engineering. Int J Biol Macromol 1999;25:111–21.
[102] Singh S, Maxwell D. Tools of the trade. Best Prac Res Clin Obst Gyn 2006;20:41-59.
[103] Shishatskaya EI, Volova TG, Puzyr AP, Mogilnaya OA, Efremov SN. Tissue response to the implantation of biodegradable polyhydroxyalkanoate sutures. J Mater Sci-Mater M 2004;15: 719-28.
[104] Volova T, Shishatskaya E, Sevastianov V, Efremov S, Mogilnaya O. Results of biomedical investigations of PHB and PHB/PHV fibers. Biochem Eng J 2003;16:125-33.
[105] Baptist JN, Ziegler JB. Method of making absorbable surgical sutures from poly beta hydroxyacids. US Patent No: 3225766, 1965.
[106] Shishatskaya EI, Volova TG, Puzyr AP, Mogilnaya OA and Efremov SN: Tissue response to the implantation of biodegradable polyhydroxyalkanoate sutures. J Mater Sci Mater Med 2004;15:719-28.
[107] Misra SK, Valappil SP, Roy I, Boccaccini AR. Polyhydroxyalkanoate (PHA)/inorganic phase composites for tissue engineering applications. Biomacromolecules 2006;7:2249-58.
[108] Ni J, Wang M. In vitro evaluation of hydroxyapatite reinforced polyhydroxybutyrate composite. Mater Sci Eng C-Bio S 2002;20:101-9.
[109] Luklinska ZB, Bonfield W. Morphology and ultrastructure of the interface between hydroxyapatite-polyhydroxybutyrate composite implant and bone. J Mater Sci-Mater M 1997;8:379-83.
[110] Chen LJ, Wang M. Production and evaluation of biodegradable composites based on PHB-PHV copolymer. Biomaterials 2002;23:2631-9.
[111] K?se GT, Korkusuz F, Korkusuz P, Hasirci V. In vivo tissue engineering of bone using poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) and collagen scaffolds. Tissue Eng2004;10:1234-50.
[112] Wang YW, Wu QO, Chen GQ. Attachment, proliferation and differentiation of osteoblasts on random biopolyester poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) scaffolds. Biomaterials 2004;25:669-75.
[113] Wang YW, Wu Q, Chen JC, Chen GQ. Evaluation of threedimensional scaffolds made of blends of hydroxyapatite and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) for bone reconstruction. Biomaterials 2005;26:899-904.
[114] Yang M, Zhu SS, Chen Y, Chang ZJ, Chen GQ, Gong YD, Zhao NM, Zhang XF. Studies on bone marrow stromal cells affinity of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate). Biomaterials 2004; 25:1365-73.
[115] Hu YJ, Wei X, Zhao W, Liu YS, Chen GQ. Biocompatibility of poly(3- hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) with bone marrow mesenchymal stem cells. Acta Biomater 2008;5:1115-25.
[116] L?bler M, SaX M, Schmitz KP, Hopt UT. Biomaterial implants induce the inflammation marker CRP at the site of implantation. J Biomed Mater Res 2003;61:165-7.
[117] Behrend D, Nischan C, Kunze C, Sass M, Schmitz KP. Resorbable sacffold for tissue engineering. Med. Biol. Eng. Comput. 1999;37:1510-1.
[118] Fukuda S, Sakai N, Kamata SE, Nameki H, Kishimoto S, Nishikawa N, Kaneko S, Miyata M, Fujii M, Inuyama Y. Surgical results of skull base surgery for the treatment of head and neck malignancies involving skull base: multi-institutional studies on 143 cases in Japan. Auris Nasus Larynx 2001;28:S71-5.
[119] Bowald SF, Johansson EG. A novel surgical materials. Eurpean Patent No. 0349 505 A2, 1990.
[120] Janousek P, Kabelka Z, Rygl M, Lesny P, Grabec P, Fajstavr J, Jurovcík M, Snajdauf J. Corrosive injury of the oesophagus in children. Int J Ped Otorhinol 2006;70:1103-7.
[121] Williams SF, Martin DP. Application of PHAs in Medicine and Pharmacy. In: Doi Y, Steinbüchel A, editors. Biopolymers, vol. 10. Weinheim: Wiley-VCH; 2002, p. 91-121.
[122] Opitz F, Schenke-Layland K, Richter W, Martin DP, Degenkolbe I, Wahlers T, StockUA. Tissue engineering of ovine aortic blood vessel substitutes using applied shear stress and enzymatically derived vascular smooth muscle cells. Ann Biomed Eng 2004;32:212-22.
[123] Opitz F, Schenke-Layland K, Cohnert TU, Starcher B, Halbhuber KJ, Martin DP, StockUA. Tissue engineering of aortic tissue: dire consequence of suboptimal elastic fiber synthesis in vivo. Cardiovasc Res 2004;63:719-30.
[124] Qu XH, Wu Q, Liang J, Qu X, Wang SG, Chen GQ. Enhanced vascular-related cellular affinity on surface modified copolyesters of 3-hydroxybutyrate and 3-hydroxyhexanoate (PHBHHx). Biomaterials 2005;26:6991-7001.
[125] Qu XH, Wu Q, Zhang KY, Chen GQ. In vivo studies of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) based materials: biodegradation and tissue reactions. Biomaterials 2006;27:3540-8.
[126] Qu XH, Wu Q, Liang J, Zou B, Chen GQ. Effect of 3-hydroxyhexanoate content in poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) on in vitro growth and differentiation of smooth muscle cells. Biomaterials 2006;27:2944-50.
[127] Qu XH, Wu Q, Chen GQ. In vitro study on hemocompatibility and cytocompatibility of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate). J Biomater Sci Polym Ed 2006;17:1107-21.
[128] Sodian R, Hoerstrup SP, Sperling JS, Daebritz S, Martin DP, Moran AM, Kim BS, Schoen FJ, Vacanti JP, Mayer JE. Early in vivo experience with tissue-engineered trileaflet heart valves. Circulation 2000;102(Suppl.):22-9.
[129] Martin DP, Williams SF. Medical applications of poly 4-hydroxybutyrate: a strong flexible absorbable biomaterial. Biochem Eng J 2003;16:97-105.
[130] Sodian R, Loebe M, Hein A, Martin DP, Hoerstrup SP, Potapov EV, Hausmann H, Lueth T, Hetzer R. Application of stereolithography for scaffold fabrication for tissue engineered heart valves. ASAIO J 2002;48:12-6.
[131] Hazari A, Johansson-Rudén G, Junemo-Bostrom K, Ljungberg C, Terenghi G, Green C, Wiberg M. A new resorbable wrap around implant as an alternative nerve repair technique. J Hand Surg 1999;24:291-5.
[132] Ljungberg C, Johansson RG, Bostrom KJ, Novikov L, Weiberg M. Neuronal survival using a resorbable synthetic conduit as an alternative to primary nerve repair. Microsurgery 1999;19:250-64.
[133] Hazari A, Wiberg M, Johansson RG, Green C, Terenghi G. A resorbable nerve conduit as an alternative to nerve autograft in nerve gap repair. Br J Plast Surg 1999;52:653-7.
[134] Mosahebi A, Fuller P, Wiberg M, Terenghi G. Effect of allogeneic schwann cell transplantation on peripheral nerve regeneration. Exp Neurol 2002;173:213-23.
[135] Li J, Li L, Ren BC. Experimental study of the eyelid reconstruction in situ with the acellular xenogeneic dermal matrix. Chin J Plast Surg 2007;23:170-4.
[136]侯忠敏,荣运久.眼科基础与临床问答.北京:人民军医出版社; 1998. p. 9-10.
[137]杨安峰,王平.大鼠的解剖和组织.北京:科学出版社; 1985. p. 34.
[138] Goldberg RA, Joshi AR, McCann JD, Shorr N. Management of severe cicatricial entropion using shared mucosal grafts. Arch Ophthalmol 1999;117:1255-9.
[139] Chen JQ, Gu JJ, Peng HJ, Huang T, Chen LS, et al. The eyelid reconstruction in situ with allograft acellular dermal matrix. Chin J Ophthalmol 2005;41:409-13.
[140] Mannor GE, Mathers WD, Wolfley DE, Martinez JA. Hard-palate mucosa graft in Stevens-Johnson syndrome. Am J Ophthalmol 1994;118:786-91
[141] Wójcicki P, Kobus K. Treatment of entropion using mucous membrane and cartilage graftsfrom the nasal septum. Klin Oczna 2006;108:431-3.
[142] Tenzel RR, Miller GR, Rubenzik R. Cicatricial upper lid entropion: treated with banked scleral graft. Arch Ophthalmol 1975;93:999-1000.
[143] Ren BC, Zhao JQ, Zhang J. Experimental study on eyelid reconstruction with acellular xenogenic dermal matrix. Chin J Ophthalmol 2007;43:906-11.
[144] Sabate FN, Buesseler JA, Krosney NM, Yamashita T. Experimental and clinical studies of glycerin preserved scleral homografts. Eye Ear Nose Throat Monthly 1967;46:1162-6.
[145] Seiff SR, Chang JS, MH Hurt, Khayam-Bashi H. Polymerase chain reaction identification of human immunodeficiency virus-1 in preserved human sclera. Am J Ophthalmol 1994;118:528-30.
[146] McCord C, Nahai FR, Codner MA, Hester TR. Use of porcine acellular dermal matrix (Enduragen) grafts in eyelids: a review of 69 patients and 129 eyelids. Plast Reconstr Surg 2008;122:1206-13.
[147] Aragona F. Is bovine collagen safe? J Urol 1991;97:279-81.
[148] Srivastava A, Jennings LJ, Hanumadass M, Sethi S, DeSagun E, Pavlis N, Reyes H, Walter RJ. Xenogeneic acellular dermal matrix as a dermal substitute in rats. J Burn Care Res 1999;20:382-90.
[149] Clark G. Staining procedures. Baltimore: Williams and Wilkins; 1973, p. 33-5.
[150] Cheng ST, Chen ZF, Chen GQ. The expression of cross-linked elastin by rabbit blood vessel smooth muscle cells cultured in polyhydroxyalkanoate scaffolds. Biomaterials 2008;29:4187-94.
[151] The Association for Research in Vision and Ophthalmology. Statement for the use of animals in ophthalmic and vision research. In: Animals in Research Committee, editor. Handbook for the use of animals in biomedical research. Bethesda: The Association forResearch in Vision and Ophthalmology; 1993. p. 15-16.
[152] Stocum DL. Regenerative biology and medicine. Oxford: Elsevier Science; 2006. p. 21-36.
[153] Anderson JM. Biological responses to materials. Annu Rev Mater Res 2001;31:81-110.
[154] Jutila MA. Leukocyte traffic to sites of inflammation. APMIS 1992;100:191-201.
[155] Cotran RZ, Kumar V, Robbins SL, editors. Pathologic basis of disease. Philadelphia: Saunders; 1979. p. 50-112.
[156] Williams GT, Williams WJ. Granulomatous inflammation--a review. J Clin Pathol 1983;36:723-33.
[157] Lanza RP, Langer R, Chick WL. Principles of tissue engineering. Austin: Academic Press; 1997.
[158] B?stman OM. Absorbable implants for the fixation of fractures. J Bone Joint Surg Am 1991;73:148-53.
[159] Williams SF, Martin DP. Applications of PHAs in medicine and pharmacy. In: Doy I, Steinbuchel A, editors. Biopolymers polyesters III. Weinheim: Wiley-VCH; 2001. p. 91-127.
[160] Rashid ST, Salacinski HJ, Hamilton G, Seifalian AM. The use of animal models in developing the discipline of cardiovascular tissue engineering: a review. Biomaterials 2004;25:1627–37.
[161] Shishatskaya EI, Volova TG, Puzyr AP, Mogilnaya OA, Efremov SN. Tissue response to the implantation of biodegradable polyhydroxyalkanoate sutures. J Mater Sci Mater Med 2004;15:719-28.
[162] Anderson JM. Mechanisms of inflammation and infection with implanted devices. Cardiovasc Pathol 1993;2:33-41.
[163] Anderson JM. Inflammatory response to implants. ASAIO Trans 1988;34:101-7.
[164] Rae T. The macrophage response to implant materials. Crit Rev Biocompatibility 1986;2:97-126.
[165] Chambers TJ, Spector WG. Inflammatory giant cells. Immunobiology 1982;161:283-9.
[166] Anderson JM. Biological responses to materials. Annu Rev Mater Res 2001;31:81-110.
[167] Srivastava A, DeSagun EZ, Jennings LJ, Sethi S, Phuangsab A, Hanumadass M, Reyes HM, Walter RJ. Use of porcine acellular dermal matrix as a dermal substitute in rats. Ann Surg 2001;233:400-8.
[168] Schoen FJ, Mitchell RN. Tissue, the extracellular matrix, and cell-biomaterial interactions. In: Ratner BD, Hoffman AS, Schoen FJ, Lemons JE, editors. Biomaterials science: an introduction to materials in medicine. Singapore: Elsevier science Pte Ltd; 2004. p. 260-81.
[169] Williams DF. On the nature of biomaterials. Biomaterials 2009;30:5897-909.