治疗短鼻畸形的可控性膨胀材料的实验研究
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摘要
研究背景
     短鼻畸形的有效矫正一直是鼻整形外科中的一个难题。针对短鼻畸形所具有的钝性鼻唇角、鼻尖上翘、鼻长高比例失调,鼻面角小、上唇长等特点,产生了各种矫正手术方法,但是这些处理手段和方法存在需要多次手术,瘢痕较明显,移植支架组织量大容易造成血运障碍等问题。鼻支撑结构的可无限延长与鼻软组织覆盖量的供应不足,使得短鼻延长效果远远达不到理想要求。
     近年来随着要求鼻子延长求美者的日益增多,使得短鼻延长术又成为鼻整形的新热点。无论是用自体软骨或者骨组织块,还是各种人工合成材料的鼻支架,都可以用作鼻的延长,但是随访发现一次性过度延长的支架所引起的鼻尖破溃并发症发生率较高。要从根本上杜绝这些并发症的发生,就要在延长支架结构的同时充分估计鼻部覆盖皮肤软组织是否足够,所以鼻部覆盖皮肤软组织量的足够与否成为制约短鼻延长的关键问题。
     要获得增加额外的皮肤软组织量,又不需要移植皮肤,目前最佳的办法是皮肤软组织扩张术,然而鼻部结构特殊,又兼具呼吸功能,若在鼻部应用皮肤软组织扩张器有很大的难度,而且即使应用,也要面临两次手术和不断注水的麻烦,严重影响病人的正常生活和工作;并且由于个体的鼻子形态不同,每个求美者个性化要求也各有所异,这又增加了鼻部皮肤软组织扩张器应用的难度。故虽有学者曾经尝试过鼻部扩张器的研发,但至今在文献检索中仍未见这方面的正式报道。
     解决短鼻的延长的关键在于如何能提供额外的鼻部软组织覆盖量。为了解决短鼻延长治疗中的皮肤软组织覆盖不足,减少手术并发症我们拟研制一种类似皮肤软组织扩张器可在体内自行膨胀延长的材料,既可以充当鼻支架,又具有自动膨胀达到扩张皮肤要求,可以根据鼻子的具体情况,设计鼻延长假体并控制这种材料的膨胀量大小形状,膨胀方向,膨胀时间和膨胀的速度,以保证这种材料在临床使用中安全和有效,一次手术就同时解决鼻支架结构延长和增加鼻软组织覆盖的问题。
     目前最常用的短鼻延长支架为医用硅橡胶,是公认的比较安全的人体植入材料,但不具备扩张膨胀的特性。医用水凝胶(hydrogel)是一类具有亲水性但不溶解于水,只在水中发生溶胀的高分子材料,水凝胶可溶胀产生大于其自身几倍、几十倍或更多的体积,并具有可以接枝到力学性能较好的基材上特性,然而能否将此种材料用作可控性鼻支架尚未有相关研究。
     研究目的
     本课题旨在探讨一种可控性的鼻支架植入短鼻内,令其缓慢膨胀延长,使鼻部皮肤得到缓慢扩张,以减少并发症。为今后短鼻畸形的治疗提供一新的治疗途径。
     研究内容
     1.结合临床手术观察,通过尸体标本鼻部解剖,找出鼻支架结构中与鼻延长有关的结构,并测量通过手术分离可以延长的程度,再用螺旋CT进行鼻部扫描重建,观察鼻部浅表结构,全面认识鼻延长的解剖学基础。
     2.在以往硅胶改性和医用水凝胶的研究基础上,寻找能够与医用硅橡胶相复合的医用水凝胶,制备出既可以自动膨胀代替皮肤软组织扩张器又可以充当鼻部延长永久性支架的复合材料。通过不同比例配方获得不同程度膨胀的量,实现定量扩张;同时通过梯度复合技术控制复合膨胀材料的膨胀的方向,达到复合材料可控膨胀的目的。
     3.对可控性膨胀材料和纯硅胶材料的内部结构进行对比观察和体外回缩实验明确膨胀机理。通过体外膨胀实验观察复合膨胀材料的定向膨胀的可行性。
     4.对照体外实验,将不同比例的SR/PVPP复合膨胀材料植入动物皮下,同体对比观察不同比例SR/PVPP复合膨胀材料和纯硅胶假体是否具有一样或者更好的组织相容性,并从中优化筛选出下一步实验用最佳比例复合膨胀材料。
     5.SR/PVPP复合膨胀材料植入兔鼻尖部,与空白(不植入任何材料)及植入纯硅胶假体试验组形成对照研究;通过观察鼻尖皮肤的血流变化和基底细胞的有丝分裂,证明这种SR/PVPP复合膨胀材料对局部皮肤软组织确实具有扩张的作用:局部皮肤获得生物性增生额外增加的皮肤。
     6.通过核磁共振(MRI)无创性动态观察,为今后这种材料的临床应用提供一个实用的监测手段,同时更加证明这种材料的一次性软组织扩张的有效性。材料与方法
     1.短鼻延长的解剖学基础研究
     按照鼻部整形手术的正常步骤进行2具陈旧成年尸体头颅标本,6具新鲜成年尸体头颅标本鼻子的局部分层解剖。在一定的拉力下测量每个标本鼻翼软骨与侧鼻软骨分离度。在彻底分离开侧鼻软骨和鼻翼软骨之间的联系,保留侧鼻软骨与鼻翼软骨之间鼻粘膜的完整联系时测量两者间距离。
     应用美国CE公司LightSpeed 16排螺旋CT以5mm断层扫描并进行分拆后的图像数据传输到HP workstation XW8000工作站上进行鼻部软组织重建,显示出鼻部软组织结构(鼻软骨)的构图,直接反应术前和术后的情况。
     2.可控性膨胀材料的合成和表征
     用成都有机硅中心生产的医用甲基乙烯基混炼硅橡胶与自制PVPP于开炼机上混炼均匀,室温停放24小时后,置于模具内,在已预热过的平板硫化机上160℃,3MPa下硫化15分钟后取出;二段硫化:鼓风干燥箱内鼓风进行,180℃保温四小时,即得SR/PVPP复合材料。对这种复合材料进行形态分析、亲水性能测试和吸水膨胀性能测试。
     3.可控性膨胀材料的内部结构观察、回缩实验及定向材料的制备。通过Hitachi S-3000型扫描电镜观察SR/PVPP复合膨胀材料和纯硅胶假体材料膨胀前后内部结构形态的变化。
     将不同配方的复合膨胀材料放入生理盐水量杯中膨胀,在达到平衡后(不再变化),将材料取出晾干,每天观察和测量材料膨胀长度和体积的变化。
     利用梯度复合工艺把纯硅胶与复合膨胀材料结合在一起,制造出整块的梯度复合材料,并根据临床使用的要求,雕刻出不同的假体形状,在放入生理盐水中,观察定向扩张的表现。
     4.不同比例可控性SR/PVPP复合膨胀材料在动物皮下植入的反应观察根据拉丁方统计设计原理,选择6×6基本拉丁方来安排6种比例SR/PVPP可控性复合膨胀材料在同一只兔子背部皮下进行对比研究。一共观察6只成年新西兰兔,36块材料,每天人工测量并记录每只兔子的皮下假体的长度变化。在6周后进行测量数据的统计学拉丁方设计资料的方差分析。通过组织切片对比纯硅胶材料,观察复合膨胀材料纤维包膜反应,研究该材料的组织相容性
     5.同一比例可控性复合膨胀材料鼻尖部植入,与空白及对照组对比观察鼻尖皮肤血流及有丝分裂情况
     将14只成年新西兰兔分成三组,实验组兔子鼻尖皮下埋入25%比例SR/PVPP复合膨胀材料假体,同时设立空白对照和试验对照(0%PVPP纯硅胶材料)定期用ES-1000血流多普勒检测仪测量血流流速和峰值,再按照术后3、7、9、14、30、60、90天从喂养的实验组兔子中随机选一只取鼻尖部皮肤做样本,同时从对照组兔子鼻部相同位置取皮肤样本,一起做HE染色组织切片,用光学显微镜观察的组织切片,拍摄不同放大倍数的组织切片图。在高倍镜下以一个视野为单位进行上皮组织基底细胞的有丝分裂细胞数。
     6.可控性复合膨胀材料鼻尖部植入后的检测---MRI动态观察
     用西门子Magneton Impact Expert 1.5T超导磁共振机,用头线圈,对猫和兔子进行空白对照,纯硅胶实验对照和25%SR/PVPP复合材料实验组观察按照术前,术后即时,术后3天,7天,10天,16天,35天分别将上述三组动物在全身麻醉下进行MRI扫描。
     结果:
     1.我们通过尸体解剖和临床手术活体结构的观察,发现和证实了鼻子支撑结构中鼻骨与侧鼻软骨呈重叠连接、中隔软骨与侧鼻软骨呈融合延续连接、侧异软骨与鼻翼软骨呈钩袢连接。其中侧鼻软骨与鼻翼软骨在一定的拉力(支撑力)的作用下,在充分分离两者之间联系,保持连接处下方的粘膜完整的条件下正中位置最大可以向前延伸长7.04 mm,平均延伸5.98 mm,侧边最大可以向前延伸5.03mm,平均延伸3.92mm。
     16排螺旋CT断层扫描并进行鼻部软组织重建,能够清晰显示出鼻部软组织结构特别是鼻软骨的构图。
     2.以医用甲基乙烯基硅橡胶为基体,自制的交联聚乙烯基吡咯烷酮水凝胶(PVPP)为吸水组分,用物理共混法制备了可吸水膨胀的硅橡胶/PVPP水凝胶复合材料。我们用接触角测试结果表明,医用甲基乙烯基硅橡胶中引入PVPP水凝胶后,材料表面亲水性能显著提高。体外膨胀实验证明复合材料随PVPP含量的增加,吸水膨胀体积增加。
     3.通过扫描电镜观察SR/PVPP复合膨胀材料和纯硅胶假体材料膨胀前后内部结构形态的变化,可以明显显示两种材料内部完全不同的形态变化。分布在硅胶中的PVPP颗粒在遇水后,可以自行膨胀来使复合膨胀材料整体膨胀。同时我们获得了定向膨胀的SR/PVPP复合膨胀材料。
     4.按6×6基本拉丁方来安排6种不同比例PVPP硅胶可控性复合膨胀材料在同一只兔子背部皮下进行对比研究,与纯硅胶假体比较具有明显的膨胀特点,统计学结果分析两者间有显著差异(P<0.001)。SR/PVPP复合膨胀材料具有良好的组织相容性。25%的SR/PVPP复合膨胀材料膨胀程度适中,是下一步实验中比较安全的鼻尖植入假体。
     5.25%的SR/PVPP复合膨胀材料可以作为合适的鼻尖实验用复合膨胀材料。与空白(不植入任何材料)及植入纯硅胶假体试验组形成对照研究,25%PVPP硅橡胶复合膨胀材料植入兔鼻尖部后,能够明显膨胀并引起鼻尖皮肤的血流增加和基底细胞有丝分裂增加,完全符合局部皮肤得到有效扩张的表现。
     6.通过核磁共振(MRI)无创性动态观察,能够清楚显示出不同时间皮下复合膨胀材料的膨胀变化过程。为今后这种材料的临床应用提供一个实用的监测手段,同时再次证明这种材料的皮肤软组织扩张的有效性。
     结论:
     1.在鼻骨、侧鼻软骨、中隔软骨与鼻翼软骨构建的鼻支架关系中,侧鼻软骨与鼻翼软骨之间的结合特点是短鼻延长的解剖学基础。侧鼻软骨与鼻翼软骨在一定的支撑力的作用下,在充分分离开两者之间的联系后可以鼻子支架和粘膜可以被同时向前延伸。
     2.硅胶和PVPP通过物理混合的方法制备出可吸水膨胀的SR/PVPP复合材料,其表面亲水性能显著提高,两者理化性质保持不变,可以通过自身水凝胶的膨胀引起整体增大,随着PVPP含量的增加,膨胀体积增加达到平衡。
     3.SR/PVPP复合材料与纯硅胶对比,具有明显的膨胀特点,统计学结果分析两者间有显著差异。其中PVPP比例为25%的复合膨胀材料膨胀性能适中,较为适合在鼻尖实验应用。SR/PVPP复合材料能够明显延长鼻尖并引起鼻尖皮肤的血流增加和基底细胞有丝分裂增加,使局部皮肤得到生物学增生,达到鼻尖有效扩张的目的。
     4.现代影像学技术(CT/MRI)能够动态无创地显示鼻部软组织结构,并能作为今后这种新型材料临床应用的检测手段。
Background
     Lengthening the short nose is arguably the most difficult operation in aesthetic rhinoplasty.There are so many techniques to treatment the different characteries such as an obtuse columellarlabial angle,an overprojecting tip and a shallow slope of the dorsum.Of course the length of the nose is short.But all of these methods always accompany with some complications:needing several times operations,lefting more scar on the nose and the recipient site ischemia after getting much more grafts from donor site.We can lengthening the nose frame no limited with different implants, but the nose soft tissue covering is shortage! So we can not reach to our ideal desire for lengthening the nose.
     More and more cosmetic requirements have made us to look for the useful ways for lengthening the nose.We can use the autos cartilages or bone grafts,or artificial implants to make the nose longer,but so many papers reported the complication about the nose tip broken after putting over long implants in the nose.We should avoid this serious complication with sufficient estimate for the nose soft tissue covering enough when we lenghtening the nose.So it is the key point in our treatment for the short nose to get enough covering,not only the frame.
     The best way to get the epactal skin coveting is the soft tissue expandsion.But is is so difficuty to bury the expander in the nose because of it complex construction and with the important breath function.It is not easy to accept the way even we use the expander in the nose with injection water continue and twice operations trouble.Another problem for use the expander in the nose is the nose shape is so individual.So there is not any formal report about using expander on the nose.
     How to solve the problem that we face the nose soft tissue covering insufficient?
     We imagine an idea creating the automatic expanding implant just like the soft tissue expander in the nose.We can make the desige the implant size,shape and the expand direction and time(speed) according the patient and the doctor requirments. We use this kind of automic expand implant can make more soft tissue coveting for lengthening the nose frame at the same time.
     The silicone nose implant is the most common to use for lengthening the short nose.It is the idea implant material received in the world.But it is not of the expand ability.The hydrogel is the polymers with hydrophilicity.It can expand to be much times size in water but not dissolve in water.It can also inoculate to some material with better mechanical property.Both of them can just meet our requirement for the automatic expanding implant.It can fill the vacuilty in rhinoplasty implant research in the world.
     Reasearch Purpose
     1.To study the nose frame anatomy through the dissection for the different aparts in nose hard structure to find the foundation for lengthening nose.To look for the useful method to observe the nasal cartilage without operation.
     2.Use the silicone and the hydrogel to creat a new composite automatic expanding implant with both of expand and support features.To make this implant to be controlled the size and the direction by different PVPP rate and the hard silicone as prohibit the expand direction we do not want.
     3.To study the expand property through the electron microscope observe the structure inside SR/PVPP automatic composite implant.
     4.To study the different expand property and histocompatibility between the SR/PVPP automatic composite implant and pure silicone implant in the same rabbit back using 6 different PVPP rate from 0%to 35%.
     5.To study the effective expanding in the rabbit nose tip through observe the skin stroma cell mitochysis and the local blood variations.
     6.To look for the useful way to observe the automatic expand SR/PVPP implant change in the body.
     Material and Methods
     1.Lenghtening short nose basic anatomy research
     We dissect the nasal strcture on the surfacial 2 fixation cadavers and 6 fresh cadavers.We measure the separating distance between the upper lateral cartilage and the lower lateral cartilage after dissecting their connection lefting integrated the mucosa when we pull the nose tip with 300g force.We chose the 3 points to measure, the middle and both sides.Except the cadaver disscttion,we use the US CE co.ltd CT to scan the nose in 5mm and use the HP workstation XW8000 workstation to reconstruction nasal soft surface frame.
     2.SR/PVPP controllability automatic expand implant synthesis and exosyndrome
     We mix the medical methylvinylsilicone and PVPP in the special machine,let the mixing material stay in room temperature 24hours.Then we put it in another machine under 160℃/3MPa 15min.At last we put it into dry blast machine under 180℃for 4 hours.After those procedures,we get the SR/PVPP composite implant.We test the implant properties including the countenances,the hydrophilicity and the hydrating expanding.3.
     3.We use the Hitachi S-3000 type electron microscope to observe the different structure between the SR/PVPP composite implant and the pure SR implant.We observe the changes for the SR/PVPP composite implantswith different PVPP rate after expanding in saline in the dry condition.We measure the implants length and volume.To study the SR/PVPP composite implant internal structure,observe the recovery test for this implant and test the controlled direction expanding.We use the gradient compound technique to make the silicone and the SR/PVPP composite implant to be the lateralization expanding implant.
     4.To observe the body responses to the different PVPP rate SR/PVPP composite implants in the rabbit body.
     We put 36 cakes SR/PVPP composite implants with 6 different PVPP rate into the different site on the rabbit back according the Latin square statistical design.We buried 6 different PVPP rate composite implants in the same rabbit back.We measured the lenghter of the rabbit nose with the new implant everyday.We analysis the result after 60days we put in the implant.
     5.We divide 14 rabbits to three groups(SR/PVPP composite implant group,SR implant group and no implant group).We use ES-1000type Doppler to test the nose tip skin blood flow rate and the peak value。Then we random chose a rabbit to get the nose tip skin sample to do the HE hitological section 3、7、9、14、30、60、90days after inset the implant into the nose tip.We use the microscope to get the pictures in high power lens and count the cell mitochysis number in the skin stroma continuously in the different day after input the implant..
     6.We use Siemens Magneton Impact Expert 1.5T MRI to test the different implant in the different animal groups(cats and rabbits).We check the cats or rabbits nose tip with or without implant 3,7,10,16,35days after putting the implant into the nose tip continuously.All the animals are all under general anaesthesia.
     Result:
     1.Through the dissection for the different aparts in nose hard structure we found the connection between the ULC and theLLC is the foundation for lengthening nose. The largest separating distance in the middle is 7.04 mm,average 5.98 mm and,the The largest separating distance in the side is 5.03mm,average 3.92mm between the ULC and the LLC after dissecting their connection lefting integrated mucosa with 300g pull force.The CT to scan the nose and the HP workstation XW8000 workstation are the useful method to observe the nasal cartilage without operation.
     2.According the researches for silicone reshaping and the medical hydrogel application before,we use the silicone as the basal body to composite with the PVPP (as the water absorb component) to create new automatic expand composite implants. Contact angle results indicated that after the introduction of PVPP hydrogel,the surface hydrophilic properties of silicone rubber material were significantly improved. The water swelling properties and mechanical properties were also investigated.And it was found that,with the increasing of PVPP content,composites' volume swelling ratio increased while mechanical properties decreased.And the equilibrated volume swelling ratio in physiological saline was similar with deionized water.
     3.After studying the SR/PVPP composite implant internal structure,we found that the PVPP is the reason for SR/PVPP composite implant expanding when it meet water.We found that the SR/PVPP composite implants with different PVPP rate can be recover to original size and shape after expanding in saline in the dry condition.
     Using the gradient compound technique we creaded the silicone and the SR/PVPP composite implant to be the lateralization expanding implant.
     4.We put 36 cakes SR/PVPP composite implants with 6 different PVPP rate into the different site on the rabbit back according the Latin square statistical design.We found that the SR/PVPP composite implants can expand notably.There is a significant deviation between the SR/PVPP composite implant and the SR implant.The experiment result showed us the optimization PVPP rate is 25%.From our test,we have discovered that PVPP-silicone composite expand implant has better histocompatibility than the pure silicone implant.
     5.We put the 25%SR/PVPP composite implant t the nose tip in 9 rabbits.At same time,we put the pure silicone implants in another rabbits nose tip.We made the control study among the 25%SR/PVPP composite implant,silicone implant and not any implant(blank).We found that the 25%SR/PVPP composite implant can expand the local skin soft tissue effectively through the study the nose tip skin blood flow and the skin epicyte karyokinetic division.
     6.We also use the MRI in dynamic state to observe the SR/PVPP composite implant in the cats and rabbits body.The result has proved that the SR/PVPP composite implant could expand the soft tissue and to be the implant in the nose.
     Conclution:
     1.Through the dissection for the different aparts in nose hard structure we found the connection between the ULC and theLLC is the foundation for lengthening nose.
     2.After the SR and PVPP mixed with the physical way,the surface hydrophilic properties of silicone rubber material were significantly improved.With different PVPP rate the increasing of PVPP content,composites' volume swelling ratio increased.And the equilibrated volume swelling ratio in physiological saline was similar with deionized water.Using the gradient compound technique we treaded the silicone and the SR/PVPP composite implant to be the lateralization expanding implant.The SR/PVPP composite implants can expand notably.There is a significant deviation between the SR/PVPP composite implant and the SR implant. 3.The SR/PVPP composite implant can expand the local skin soft tissue effectively through increasing the nose tip skin blood flow and the skin epicyte karyokinetic division.The SR/PVPP composite implant not only is the common implant for nose frame,but also is the expander in the nose to make more skin for nose tip.
     4.The CT to scan the nose and the soft tissue reconstruction technique are the useful method to observe the nasal cartilage without operation.MRI can be used to observe the PVPP-silicone composite implant in the bodye in dynamic,continously and no-invision.It is the useful tool to test the SR/PVPP expand implant in human body as we requirement
引文
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