Green Electrospun Silk Fibroin/Galactose Chitosan Composite Nanofibrous Scaffolds for Hepatic Tissue Engineering

The electrospun nanofibrous scaffolds made of proteins and polysaccharides were thought to be able to simulate the structure of natural extracellular matrix well.Silk fibroin(SF)and chitosan(CS)are probably the most widely used natural materials in biomedical fields including liver tissue engineering for their good properties and wide variety of sources.The asialoglycoprotein receptors of hepatocyte were reported to specifically recognize and interact with galactose.In this work,a green electrospun SF/galactosylated chitosan(GC)composite nanofibrous scaffold was fabricated and characterized.The data indicated that the addition of GC greatly influenced the spinning effect of SF aqueous solution,and the average diameter of the composite nanofibers was about 520nm.Moreover,the green electrospun SF/GC nanofibrous scaffolds were demonstrated significantly enhancing the adhesion and proliferation of hepatocyte(RH35)according to our data.The present study did a useful exploration on constructing scaffolds for liver regeneration by green electrospinning,and also laid a good foundation for the further applicative research of this green electrospun scaffolds in liver tissue engineering.

VE TPGS-Loaded Silk Fibroin / Hydroxybutyl Chitosan Nanofibrous Scaffolds for Skin Care Application

Vitamin E( VE) is an ideal antioxidant and a stabilizing agent in biological membranes. In this study,silk fibroin( SF) /hydroxybutyl chitosan( HBC) nanofibrous scaffolds are loaded with VE tocopherol polyethylene glycol 1000 succinate( VE TPGS) via electrospinning. SEM images show that the average nanofibrous diameter has no significant difference when the content of VE TPGS increases to 4. 0%( SF / HBC). However,the average nanofibrous diameter decreases largely to 200 nm when the VE TPGS content reaches 6. 0%. Furthermore,VE TPGS presents a sustained release behavior from the nanofibrous scaffolds. Cell viability studies of mouse skin fibroblasts( L929) demonstrate that VE TPGS loaded SF / HBC nanofibrous scaffolds present good cellular compatibility.Moreover,the incorporation of VE TPGS could strengthen the ability of SF / HBC nanofibrous scaffolds on protecting the cells against oxidation stress using the Tertbutyl hydroperoxide( t-BHP)-induced oxidative injury model. Therefore,VE TPGS-loaded SF /HBC nanofibrous scaffolds might be potential candidates for personal skin care,wound dressing and skin tissue engineering scaffolds.

Silk Fibroin Scaffolds Direct Neural and Glial Differentiation from Embryonic Stem Cells

Spinal cord injury repair is one of the major challenges in medicine,as it can lead to permanent loss of function of central nervous system and damage to other function of the body.Stem cell transplantation together with tissue engineering is increasingly becoming a potential choice of treatment.However,direct transplantation of stem cells without scaffolds has yielded poor clinical outcome.Here we show a strategy of using mouse embryonic stem cells(ESCs)cultured within a silk fibroin(SF)based,three-dimensional scaffold with oriented channels by a directional temperature field freezing technique and lysophilization.We find that the ESCs maintained proliferation and migrated in the scaffolds and the cells migrated fastest along the SF channels.SF scaffolds contributed to ESC differentiation into neural and glial cell like cells and expressions of the neural and glial cell markers MAP2 and GFAP were greatly elevated when retinoic acid was used as an inducing factor.Our results suggest that this approach may offer some hope in the future for spinal cord injury repair using SF scaffolds and ESCs.

Tussah Silk Fibroin Porous Scaffolds Prepared with a Mild Self-assembly Process for Controlled Drug Release

Besides excellent biodegradability and biocompatibility,a useful tissue engineering scaffold should provide favorable surface properties,outstanding mechanical strength and controlled drug release property. In this paper,a mild process to prepare porous tussah silk fibroin( TSF) scaffolds from aqueous solution was described. The n-butanol was used to control the self-assembly of tussah silk. The scaffolds with different TSF concentrations and the same volume showed differences in pore size and distribution. The maximum porosity of the poprepared porous scaffolds was 80% in this paper. And the pore size of the prepared porous scaffolds with different concentrations was between 10μm and 230 μm. X-ray diffraction( XRD) analysis revealed that amorphous TSF was crystallized to β-sheet secondary structure upon gelatin. The TSF scaffolds for controlled drug release was studied and the result showed that the time of drug release was significantly longer. The produced TSF scaffolds with sustained drug release have potential application in tissue engineering.

Three-dimensional bioprinting collagen/silk fibroin scaffold combined with neural stem cells promotes nerve regeneration after spinal cord injury

Many studies have shown that bio-scaffolds have important value for promoting axonal regeneration of injured spinal cord.Indeed,cell transplantation and bio-scaffold implantation are considered to be effective methods for neural regeneration.This study was designed to fabricate a type of three-dimensional collagen/silk fibroin scaffold (3D-CF) with cavities that simulate the anatomy of normal spinal cord.This scaffold allows cell growth in vitro and in vivo.To observe the effects of combined transplantation of neural stem cells (NSCs) and 3D-CF on the repair of spinal cord injury.Forty Sprague-Dawley rats were divided into four groups: sham (only laminectomy was performed),spinal cord injury (transection injury of T10 spinal cord without any transplantation),3D-CF (3D scaffold was transplanted into the local injured cavity),and 3D-CF + NSCs (3D scaffold co-cultured with NSCs was transplanted into the local injured cavity.Neuroelectrophysiology,imaging,hematoxylin-eosin staining,argentaffin staining,immunofluorescence staining,and western blot assay were performed.Apart from the sham group,neurological scores were significantly higher in the 3D-CF + NSCs group compared with other groups.Moreover,latency of the 3D-CF + NSCs group was significantly reduced,while the amplitude was significantly increased in motor evoked potential tests.The results of magnetic resonance imaging and diffusion tensor imaging showed that both spinal cord continuity and the filling of injury cavity were the best in the 3D-CF + NSCs group.Moreover,regenerative axons were abundant and glial scarring was reduced in the 3D-CF + NSCs group compared with other groups.These results confirm that implantation of 3D-CF combined with NSCs can promote the repair of injured spinal cord.This study was approved by the Institutional Animal Care and Use Committee of People’s Armed Police Force Medical Center in 2017 (approval No.2017-0007.2).

Human amniotic epithelial cells combined with silk fibroin scaffold in the repair of spinal cord injury

Treatment and functional reconstruction after central nervous system injury is a major medical and social challenge. An increasing number of researchers are attempting to use neural stem cells combined with artificial scaffold materials, such as fibroin, for nerve repair. However, such approaches are challenged by ethical and practical issues. Amniotic tissue, a clinical waste product, is abundant, and amniotic epithe- lial cells are pluripotent, have low immunogenicity, and are not the subject of ethical debate. We hypothesized that amniotic epithelial cells combined with silk fibroin scaffolds would be conducive to the repair of spinal cord injury. To test this, we isolated and cultured amniotic epithelial cells, and constructed complexes of these cells and silk fibroin scaffolds. Implantation of the cell-scaffold complex into a rat model of spinal cord injury resulted in a smaller glial scar in the damaged cord tissue than in model rats that received a blank scaffold, or amniotic epithelial cells alone. In addition to a milder local immunological reaction, the rats showed less inflammatory cell infiltration at the trans- plant site, milder host-versus-graft reaction, and a marked improvement in motor function. These findings confirm that the transplantation of amniotic epithelial ceils combined with silk fibroin scaffold can promote the repair of spinal cord injury. Silk fibroin scaffold can provide a good nerve regeneration microenvironment for amniotic epithelial cells.

Novel conductive polypyrrole/silk fibroin scaffold for neural tissue repair

Three dimensional（3D） bioprinting, which involves depositing bioinks（mixed biomaterials） layer by layer to form computer-aided designs, is an ideal method for fabricating complex 3D biological structures. However, it remains challenging to prepare biomaterials with micro-nanostructures that accurately mimic the nanostructural features of natural tissues. A novel nanotechnological tool, electrospinning, permits the processing and modification of proper nanoscale biomaterials to enhance neural cell adhesion, migration, proliferation, differentiation, and subsequent nerve regeneration. The composite scaffold was prepared by combining 3D bioprinting with subsequent electrochemical deposition of polypyrrole and electrospinning of silk fibroin to form a composite polypyrrole/silk fibroin scaffold. Fourier transform infrared spectroscopy was used to analyze scaffold composition. The surface morphology of the scaffold was observed by light microscopy and scanning electron microscopy. A digital multimeter was used to measure the resistivity of prepared scaffolds. Light microscopy was applied to observe the surface morphology of scaffolds immersed in water or Dulbecco＇s Modified Eagle＇s Medium at 37℃ for 30 days to assess stability. Results showed characteristic peaks of polypyrrole and silk fibroin in the synthesized conductive polypyrrole/silk fibroin scaffold, as well as the structure of the electrospun nanofiber layer on the surface. The electrical conductivity was 1 × 10^-5–1 × 10^-3 S/cm, while stability was 66.67%. A 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyl-2-H-tetrazolium bromide assay was employed to measure scaffold cytotoxicity in vitro. Fluorescence microscopy was used to observe Ed U-labeled Schwann cells to quantify cell proliferation. Immunohistochemistry was utilized to detect S100β immunoreactivity, while scanning electron microscopy was applied to observe the morphology of adherent Schwann cells. Results demonstrated that the polypyrrole/silk fibroin scaffold was not cytotoxic and did not affect Schwann cell proliferation. Moreover, filopodia formed on the scaffold and Schwann cells were regularly arranged. Our findings verified that the composite polypyrrole/silk fibroin scaffold has good biocompatibility and may be a suitable material for neural tissue engineering.

Research on the Development of Fibroin and Nano-Fiber from Silk Cocoons for Regenerated Tissue Engineering Applications by Electro-Spinning

In this paper, the main goal is to prepare silk fibroin nano-fiber, which is used for regenerated tissue applications. Silk scaffold nano-fibers made by electro-spinning technology can be used in regenerated tissue applications. The purpose of the research is to prepare a silk-fibroin nano-fiber solution for potential applications in tissue engineering. Using a degumming process, pure silk fibroin protein is extracted from silk cocoons. The protein solution for fibroin is purified, and the protein content is determined. The precise chemical composition, exact temperature, time, voltage, distance, ratio, and humidity all have a huge impact on degumming, solubility, and electro-spinning nano-fibers. The SEM investigates the morphology of silk fibroin nano-fibres at different magnifications. It also reveals the surface condition, fiber orientation, and fiber thickness of the silk fibroin nano-fiber. The results show that regenerated silk fibroin and nano-fiber can be used in silk fibroin scaffolds for various tissue engineering applications.

A Review on Silk Fibroin as a Biomaterial in Tissue Engineering

Regenerative medicine progress is based on the development of cell and tissue bioengineering. One of the aims of tissue engineering is the development of scaffolds, which should substitute the functions of the replaced organ after their implantation into the body. The tissue engineering material must meet a range of requirements, including biocompatibility, mechanical strength, and elasticity. Furthermore, the materials have to be attractive for cell growth: stimulate cell adhesion, migration, proliferation and differentiation. One of the natural biomaterials is silk and its component (silk fibroin). An increasing number of scientists in the world are studying silk and silk fibroin. The purpose of this review article is to provide information about the properties of natural silk (silk fibroin), as well as its manufacture and clinical application of each configuration of silk fibroin in medicine. Materials and research methods. Actual publications of foreign authors on resources PubMed, Medline, E-library have been analyzed. The selection criteria were materials containing information about the structure and components of silk, methods of its production in nature. This article placed strong emphasis on silk fibroin, the ways of artificial modification of it for use in various sphere of medicine.

The degradation behavior of silk fibroin derived from different ionic liquid solvents

Establishing an appropriate degradation rate is critical for tissue engineering scaffolds. In this study, the degradation rate of silk fibroin three-dimensional scaffolds was regulated by changing the molecular weight (MW) of the silk fibroin. The solubility of silk fibroin depends primarily on the ionic ability of the slovent to dissolve silk fibroin, therefore, we regulated the MW of the silk fibroin using LiBr, Ca(NO3)2 and CaCl2 to dissolve the silk fibers. SDS-PAGE analysis showed that the MW of the CaCl2-derived silk fibroin was lower than the MW produced using LiBr and Ca(NO3)2. In vitro and in vivo degradation results showed that the scaffolds prepared by low-MW silk fibroin were more rapidly degraded. Furthermore, FTIR and amino acid analysis suggested that the amorphous regions were preferentially degraded by Collagenase IA, while the SDS-PAGE and amino acid analysis indicated that the scaffolds were degraded into polypeptides (mainly at 10-30 kDa) and amino acids. Because the CaCl2-derived scaffolds contained abundant low MW polypeptides, inter-intramolecular entanglement and traversing of molecular chains in the crystallites reduced, which resulted in rapid degradation. The in vivo degradation results suggested that the degradation rate of the CaCl2-derived scaffolds was better matched to dermis regeneration, indicating that the degradation rate of silk fibroin can be effectively regulated by changing the MW to achieve a suitable dermal tissue regeneration rate.

Novel magnetic silk fibroin scaffolds with delayed degradation for potential long-distance vascular repair

Although with the good biological properties,silk fibroin(SF)is immensely restrained in long-distance vascular defect repair due to its relatively fast degradation and inferior mechanical properties.It is necessary to construct a multifunctional composite scaffold based on SF.In this study,a novel magnetic SF scaffold(MSFCs)was prepared by an improved infiltration method.Compared with SF scaffold(SFC),MSFCs were found to have better crystallinity,magnetocaloric properties,and mechanical strength,which was ascribed to the rational introduction of iron-based magnetic nanoparticles(MNPs).Moreover,in vivo and in vitro experiments demonstrated that the degradation of MSFCs was significantly extended.The mechanism of delayed degradation was correlated with the dual effect that was the newly formed hydrogen bonds between SFC and MNPs and the complexing to tyrosine(Try)to inhibit hydrolase by internal iron atoms.Besides,theβ-crystallization of protein in MSFCs was increased with the rise of iron concentration,proving the beneficial effect after MNPS doped.Furthermore,although macrophages could phagocytose the released MNPs,it did not affect their function,and even a reasonable level might cause some cytokines to be upregulated.Finally,in vitro and in vivo studies demonstrated that MSFCs showed excellent biocompatibility and the growth promotion effect on CD34-labeled vascular endothelial cells(VECs).In conclusion,we confirm that the doping of MNPs can significantly reduce the degradation of SFC and thus provide an innovative perspective of multifunctional biocomposites for tissue engineering.

Silk fibroin-based scaffolds for tissue engineering

Silk fibroin （SF） from the Bombyx mori silkworm exhibits attractive potential applications as biomechanical materials, due to its unique mechanical and biological properties. This review outlines the structure and properties of SF, including of its biocompatibility and biodegradability. It highlights recent researches on the fabrication of various SF-based composites scaffolds that are promising for tissue engineering applications, and discusses synthetic methods of various SF-based composites scaffolds and valuable approaches for controlling cell behaviors to promote the tissue repair. The function of extracellular matrices and their interaction with cells are also reviewed here.

Random lasing detection of structural transformation and compositions in silk fibroin scaffolds

In tissue engineering, microstructure and material composition of tissue scaffolds have major influences on the proliferation and differentiation of cells in the scaffolds. However, once tissue scaffolds implanted, it is extremely difficult to monitor the change of their microstructure and compositions during tissue regeneration. Here, we report how random lasing can be utilized to non-invasively monitor the structure and composition of scaffolds. We hypothesize that morphological and compositional change of silk fibroin (SF) scaffolds can be conveniently detected based on random lasing responses. Engineered SF scaffolds with hydroxyapatite (HAP) nanoparticles and controlled pore alignment were fabricated, and their random lasing responses were analyzed depending on the concentration of HAP nanoparticles and the degree of,:internal pore alignment. We also examined the real-time random lasing responses of porous SF scaffolds by applying a compressive force to' the scaffolds. Introduction of HAP nanoparticles lowered the lasing thresholds and narrowed the random lasing (RL) width dramatically, which :is likely due to the increase in heterogeneity in both refractive index and physical arrangement within the SF and HAP composites. The strong dependency of RL response on pore alignment was also measured and validated by numerical calculation with the finite element method (FEM).Finally, real-time monitoring of RL on compressed scaffolds demonstrated the possibility of using RL as a monitoring tool for structural change of SF scaffolds in vivo.

Fabrication of glycidyl methacrylate-modified silk fibroin/poly(L-lactic acid-co-ε-caprolactone)-polyethylene glycol diacrylate hybrid 3D nanofibrous scaffolds for tissue engineering

In order to provide a biomimetic natural extracellular matrix microenvironment with excellent mechanical capacity for tissue regeneration,a novel porous hybrid glycidyl methacrylate-modified silk fibroin/poly(L-lactic acid-co-ε-caprolactone)–polyethylene glycol diacrylate(SFMA/P(LLA-CL)–PEGDA)hybrid three-dimensional(3D)nanofibrous scaffolds was successfully fabricated through the combination of 3D nanofibrous platforms and divinyl PEGDA based photocrosslinking,and then further improved water resistance by ethanol vapor post-treatment.Scanning electron microscopy and micro-computed tomography results demonstrated significant PEGDA hydrogel-like matrices bonded nanofibers,which formed a 3D structure similar to that of“steel bar(nanofibers)‒cement(PEGDA)”,with proper pore size,high porosity,and high pore connectivity density.Meanwhile,the hybrid 3D nanofibrous scaffolds showed outstanding swelling properties as well as improved compressive and tensile properties.Furthermore,these hybrid 3D nanofibrous scaffolds could provide a biocompatible microenvironment,capable of inducing the material‒cell hybrid and regulating human umbilical vein endothelial cells proliferation.They thus present significant potential in tissue regeneration.

不同肝细胞配体修饰的壳聚糖作为肝组织再生支架材料的比较研究:制备、表征和评价

为了获得理想的肝脏再生支架,使用乳酸(lactobionic acid,LA)或/和甘草次酸(glycyrrhetinic acid,GA)对壳聚糖(chitosan,CS)进行改性,得到LA改性的CS(LC)、GA改性的CS(GC)和GA/LA双改性的CS(GLC),并采用绿色静电纺丝法制备了由丝素蛋白(silk fibroin,SF)和上述改性CS组成的复合纳米纤维支架。这些支架是亲水的,其亲水性和热稳定性随着改性CS的增加而降低,而结晶度则相反。这些支架在促进HepG2细胞增殖及分泌白蛋白和尿素方面表现出良好的性能。此外,与SF/GC或SF/GLC支架相比,SF/LC支架具有更好的肝细胞相容性。

丝素蛋白联合壳聚糖基热敏水凝胶的性能评估

目的在壳聚糖(CS)/羟丙基甲基纤维素(HPMC)热敏水凝胶的基础上,利用丝素蛋白(SF)与CS交联,构建CS/HPMC/SF水凝胶,研究SF对水凝胶的性能影响。方法共混法制备CS/HPMC混合溶液,向其中分别添加1%、5%、10%的SF溶液及交联剂京尼平,加入圆柱形模具中,升温至37℃,使溶液转为凝胶态。对水凝胶进行形貌、傅里叶变换红外光谱仪(FTIR)、X射线衍射(XRD)以及亲水性及力学性能表征检测。结果扫描电子显微镜下观察水凝胶为多孔状,随着SF的加入,孔隙减少,出现裂痕。FTIR和XRD结果显示,CS与HPMC混合后结晶程度改变,当加入SF后,SF与CS发生化学交联,结构发生转变,水凝胶的亲水性也因此减弱。力学表征显示,当SF的添加量为5%时,水凝胶的回弹性最优,弹性模量最大,且基本保持不变。结论SF与CS的交联改进了CS基热敏水凝胶的性能,相比于其他组水凝胶,CS/HPMC-5%SF保持良好的亲水性且具有较好的力学性能。

丝素蛋白/明胶/壳聚糖三维多孔软骨组织支架的制备及体外评价

背景:软骨缺损是骨科医生面临的主要临床挑战之一,组织工程是一种结合了工程学和细胞生物学知识的跨学科方法,为软骨缺损的修复提供了新思路与途径。目的:基于丝素蛋白、明胶和壳聚糖制备多组分复合支架,通过评估其理化性质和生物学性能,筛选能够适合软骨再生的三维多孔支架。方法:以丝素蛋白、明胶和壳聚糖为基础材料,通过真空冷冻干燥法制备4组多孔支架,分别为明胶/壳聚糖支架、丝素蛋白/壳聚糖支架、丝素蛋白/明胶支架和丝素蛋白/明胶/壳聚糖支架,通过扫描电镜、X射线衍射、孔隙率、吸水膨胀率和生物降解率及力学性能等检测筛选出合适的软骨支架。然后将软骨支架与骨关节炎患者软骨细胞共培养,通过细胞黏附率、活死染色和增殖活性等检测体外评估多孔支架用于软骨损伤修复的可行性。结果与结论:①4组支架均具有多孔结构,综合物理性能检测结果得出丝素蛋白/明胶/壳聚糖支架更符合软骨缺损修复的要求,该支架的孔径为(176.00±53.68)μm,孔隙率为(80.15±2.57)%,吸水溶胀率为(3712±358)%,体外浸泡于含溶菌酶的PBS中28 d后的生物降解速率为(46.87±3.25)%,且具有良好的机械性能;②软骨细胞可在丝素蛋白/明胶/壳聚糖支架上良好黏附,且随着时间的延长,细胞黏附率增加;CCK8和活/死细胞双染检测结果显示,丝素蛋白/明胶/壳聚糖支架具有良好的生物相容性和较低的细胞毒性;③结果表明,丝素蛋白/明胶/壳聚糖支架具有高度水合3D结构、合适的孔径和孔隙率、良好的生物降解性能和优越的机械性能,可以为营养物质的转运和软骨细胞的附着、增殖提供良好的网状骨架和微环境。

同轴静电纺壳聚糖/聚氧化乙烯-丝素纤维的制备及其生物活性

以壳聚糖(CS)、聚氧化乙烯(PEO)和丝素蛋白(SF)为原料,采用同轴静电纺丝制备了具有核-壳结构的CSPEO-SF纤维。通过SEM、TEM和FTIR等对纤维形貌和结构进行表征分析,研究纤维的溶胀率、孔隙率和机械性能,并对其抗菌性能和体外生物活性进行评估。结果表明:所制备的纤维具有核壳结构,孔隙率均在80%以上,溶胀率最大可达675%,断裂强度最高可达7.85 MPa;该纤维对大肠杆菌和金黄色葡萄球菌均具有显著抗菌性,并且具有良好的体外生物活性,在骨组织工程领域的应用具有良好的应用前景。

丝素蛋白基骨修复材料的应用研究进展

为拓展和促进丝素蛋白材料在骨再生领域中的应用,综述了近年来丝素蛋白骨修复材料的研究进展,简要概括了丝素蛋白骨修复材料的种类和制备方法,重点阐述了丝素蛋白骨修复材料的仿生设计以及力学性能和成骨性能的调控方法。分析发现:丝素蛋白基薄膜、水凝胶和多孔支架均能诱导骨再生;调控分子量、β-折叠结构或形成定向通道可有效提高材料的力学性能;与羟基磷灰石复合不仅能提高力学性能还可促进成骨分化;同时,负载细胞或生长因子可显著增加新生骨的体积,进而修复大尺寸骨缺损。最后,总结使用丝素蛋白修复骨缺损存在的问题,并指出丝素蛋白支架的仿生设计以及保持生长因子或种子细胞的活性仍是未来研究中考虑的重点。

缓释万古霉素三维支架修复兔感染性骨软骨缺损

背景:大量研究证实组织工程支架几乎可完全修复骨软骨缺损,但当骨软骨缺损合并感染时,即使前期经过彻底的清创,单纯骨软骨组织工程支架的修复效果往往不理想。目的:制备盐酸万古霉素缓释微球丝素蛋白/壳聚糖/纳米羟基磷灰石支架,观察其对兔股骨远端感染性骨软骨缺损的修复效果。方法:①采用乳化溶剂挥发法制备盐酸万古霉素缓释微球;将不同质量(7.5,10,12.5 mg)的缓释微球分别与丝素蛋白-壳聚糖-纳米羟基磷灰石溶液混合,利用化学交联法制备盐酸万古霉素缓释微球丝素蛋白/壳聚糖/纳米羟基磷灰石支架,表征支架的孔隙率、吸水膨胀率、热水溶失率及体外药物缓释等。②将45只新西兰大白兔随机分为空白组、对照组、实验组,每组15只,均建立右后肢股骨远端骨软骨缺损并感染模型,空白组不作任何处理,对照组缺损处植入丝素蛋白-壳聚糖-纳米羟基磷灰石支架,实验组缺损处植入盐酸万古霉素缓释微球(10 mg)丝素蛋白/壳聚糖/纳米羟基磷灰石支架。术后1周,检测血液样本C-反应蛋白、白细胞水平;术后4,8,12周取术区组织,分别进行大体观察与病理学观察。结果与结论:①随着缓释微球含量的增加,支架的孔隙率降低,组间比较差异有显著性意义(P<0.05);3组支架的孔径大小、吸水膨胀率、热水溶失率比较差异均无显著性意义(P>0.05);3组支架体外均可持续释放盐酸万古霉素达30 d以上。②实验组兔血液样本C-反应蛋白、白细胞水平均低于空白组、对照组(P<0.05);实验组兔术后各时间点的大体软骨修复情况明显好于空白组、对照组;苏木精-伊红、Masson、阿利新蓝及Ⅱ型胶原免疫组化染色显示,实验组兔术后各时间点的骨软骨修复效果明显优于空白组、对照组。③结果表明,盐酸万古霉素缓释微球丝素蛋白/壳聚糖/纳米羟基磷灰石支架能有效促进开放性骨软骨缺损的修复。