可降解生物材料聚乳酸／磷酸钙陶瓷在骨组织工程中的应用

聚乳酸和磷酸钙陶瓷都是骨组织工程中常用的可降解生物材料。前者是人工合成的多聚物，在体内降解时间较长，可起到临时支架的作用，不同结构的聚乳酸又有不同的生物特性；后者生物活性好，亲和性高，但是脆性大，抗折强度低。两者的复合物在一定程度上弥补了各自的不足，能成为新型的骨组织工程支架材料。     

骨组织工程支架材料聚磷酸钙生物陶瓷研究进展

为修复创伤及病理因素导致的骨缺损,骨组织工程是一项迅速发展、不断革新的课题。多孔聚磷酸钙生物陶瓷是可吸收生物陶瓷的一种,具有良好的生物相容性以及可降解性,在骨组织工程中日益被人们所认识。骨组织工程中细胞生长速率与材料的降解速率相匹配一直是有待解决的问题,聚磷酸钙由于具有独特的结构及降解性能,因此有望解决这个问题。本文对作为骨组织工程支架材料之一的聚磷酸钙生物陶瓷的理化性质、制备方法、研究进展、骨结合机理等进行了综述,并对其研究和发展作出了展望。     

可降解生物材料聚乳酸/磷酸钙陶瓷在骨组织工程中的应用

聚乳酸和磷酸钙陶瓷都是骨组织工程中常用的可降解生物材料。前者是人工合成的多聚物,在体内降解时间较长,可起到临时支架的作用,不同结构的聚乳酸又有不同的生物特性;后者生物活性好,亲和性高,但是脆性大,抗折强度低。两者的复合物在一定程度上弥补了各自的不足,能成为新型的骨组织工程支架材料。     

骨组织工程支架材料及其血管化的研究进程

背景：随着骨组织工程学技术的不断发展,利用组织工程骨修复大面积骨缺损成为当今研究的热点。 目的：介绍骨组织工程中的种子细胞、细胞因子、支架材料的特性及材料血管化情况。 方法：以“骨组织工程,支架材料,血管化”为中文关键词,以“bone tissue engineering,scafold,vascularization”为英文关键词,采用计算机检索2000年1月至2012年1月CNKI数据库和PubMed数据库相关文章,选择与骨组织工程学概述、支架材料和血管化方面相关的文章进行分析。 结果与结论：种子细胞的选择、细胞因子的应用、支架材料的性能及血管化程度均对组织工程骨成功修复骨损伤产生着重要影响。适宜的种子细胞是骨组织工程的研究基础,细胞因子是骨组织工程研究的催化剂,具有良好三维结构的支架材料对于促进细胞的生长增殖、组织长入、成骨方式和血管化等方面均有积极的促进作用。但每种支架材料都有其不足之处,所以可以通过将多种材料进行复合达到综合效应来满足临床需求。另外也要积极寻求新的材料制备工艺和对已有方法进行改进,以制造出更加优良的支架材料。但血管化仍然是骨组织工程要面对的重大考验。目前所应用的促进组织工程骨血管化的方法均存在一定缺陷,如利用生长因子促进血管化时,易造成代谢异常患者病情恶化等情况发生;利用显微外科技术促进组织工程骨血管化,易导致其他部位形成创伤和畸形,不利于患者的身体康复等。     

骨组织工程支架材料的研究现状与应用前景CSCD

背景:目前组织工程骨修复骨缺损在临床应用中较为关键的问题是建立血管网,为新骨的形成提供氧气及营养物质,并为机体提供代谢途径。目的:综述近年组织工程骨支架材料的特点,并着重介绍复合支架材料的研究现状。方法:以"骨组织工程,血管化,支架材料,复合支架材料"为中文检索词,以"bone tissue engineering,vascularization,scaffold,composite scaffold"英文检索词,应用计算机在中国期刊全文数据库和PubMed数据库检索2001年1月至2014年1月的相关文章,将所有文章进行初步筛选后,对保留的文章进一步详细分析、归纳并总结。结果与结论:按照组织工程骨支架材料的来源不同,可将其分为人工合成材料、天然衍生材料和复合支架材料,单一支架材料难以作为最理想的材料修复骨缺损,复合支架材料能在不同程度上弥补单一支架材料的缺陷,因此近年来组织工程支架材料的发展由单一材料发展为复合材料,并呈现人工合成材料与天然材料有机结合的趋势。但复合支架材料在临床应用中仍然有许多尚待解决的问题,主要有控制复合材料比例,使材料降解速率与组织细胞的生长速率相适应,保持复合材料的多孔隙和高机械强度。     

骨组织工程支架材料的研究现状与应用前景

背景：目前组织工程骨修复骨缺损在临床应用中较为关键的问题是建立血管网,为新骨的形成提供氧气及营养物质,并为机体提供代谢途径。 目的：综述近年组织工程骨支架材料的特点,并着重介绍复合支架材料的研究现状。 方法：以“骨组织工程,血管化,支架材料,复合支架材料”为中文检索词,以“bone tissue engineering, vascularization,scaffold,composite scaffold”英文检索词,应用计算机在中国期刊全文数据库和PubMed数据库检索2001年1月至2014年1月的相关文章,将所有文章进行初步筛选后,对保留的文章进一步详细分析、归纳并总结。 结果与结论：按照组织工程骨支架材料的来源不同,可将其分为人工合成材料、天然衍生材料和复合支架材料,单一支架材料难以作为最理想的材料修复骨缺损,复合支架材料能在不同程度上弥补单一支架材料的缺陷,因此近年来组织工程支架材料的发展由单一材料发展为复合材料,并呈现人工合成材料与天然材料有机结合的趋势。但复合支架材料在临床应用中仍然有许多尚待解决的问题,主要有控制复合材料比例,使材料降解速率与组织细胞的生长速率相适应,保持复合材料的多孔隙和高机械强度。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

骨组织工程支架材料的研究进展及临床应用

背景：骨组织工程研究的中心环节是研制能够作为细胞移植与引导新骨生长的支架材料,以作为细胞外基质的替代物。 目的：总结骨组织工程支架材料的研究进展,并展望其发展趋势。 方法：由第一作者检索1995-01-12/2011-01 PubMed数据、中国知网数据库及维普数据库有关人工合成材料及天然支架材料相关文献。英文检索词为“bone tissue engineering,scaffold material,DBM,chitosan,HA,β-TCP”;中文检索词为：“骨组织工程,支架材料,细胞外基质,脱钙骨基质,壳聚糖,羟基磷灰石,β-磷酸三钙”。根据纳入标准排除重复性研究,保留30篇文献进行归纳总结。 结果及结论：支架材料是构建组织工程骨的主体,行使细胞外基质的功能,包括为组织细胞的修复活动提供适宜的微环境,抵挡来自周围组织的压力,用于承重部位暂时行使部分功能等。目前人工合成材料和天然材料各有优缺点,人工合成材料现存问题主要在于材料的细胞黏附率低,难以完全降解,致畸性和致癌性有待明确;天然材料则需要更好地解决材料的抗原性和机械性能的关系,降解速度的调控问题。充分了解现有材料的特点为寻找新方法及新材料提供理论依据。     

异种／异体骨衍生骨组织工程支架材料研究进展

支架材料是组织工程研究中的重要内容之一。本就用于骨组织工程中的异种／异体骨衍生骨支架材料的加工方法、材料的生物相容性和生物功能性进行了综述，并对需要进一步研究的内容进行了探讨。     

新型大孔隙磷酸钙骨水泥作为骨组织工程支架的相关研究

目的 探讨新型大孔隙磷酸钙骨水泥(CPC)材料支架的细胞毒性和对细胞黏附、生长和增殖的影响.方法 通过添加甘露醇制孔剂和应用磷酸钠溶液作为CPC固化液的方法合成新型CPC材料.通过CCK8法检测细胞在新型CPC材料浸提液中的生长增殖情况;通过电子扫描电镜测试材料孔径和细胞在材料表面上黏附生长情况;应用力学三点弯曲实验测试新型CPC的生物力学性能.结果 新型CPC材料的孔径值达到(267.43±118.01)μm,孔隙率为(66.15±6.91)％.新型CPC材料的最大负荷、抗弯强度和坚韧度较传统CPC均增加了约1倍(P＜0.05).新型CPC材料浸提液与细胞共培养2、4、6、8d后CCK8法测试吸光度(OD)值与阴性对照组比较其差异无统计学意义(P＞0.05).结论 新型CPC材料具有强大的生物力学性能、大孔隙、高孔隙率和良好的生物相容性,有望成为理想的骨组织工程支架.     

骨组织工程的支架材料

寻找理想的支架材料是目前骨组织工程研究的热点之一,本对用于骨组织工程支架材料的人工合成材料、天然生物衍生材料及两的复合材料的研究现状进行综述,并分析了这些材料的优缺点及骨组织支架材料今后尚待解决的问题和发展趋势。     

Biphasic calcium phosphate nanocomposite porous scaffolds for load-bearing bone tissue engineering

A novel biodegradable nanocomposite porous scaffold comprising a beta-tricalcium phosphate (beta-TCP) matrix and hydroxyl apatite (HA) nanofibers was developed and studied for load-bearing bone tissue engineering. HA nanofibers were prepared with a biomimetic precipitation method. The composite scaffolds were fabricated by a method combining the gel casting and polymer sponge techniques. The role of HA nanofibers in enhancing the mechanical properties of the scaffold was investigated. Compression tests were performed to measure the compressive strength, modulus and toughness of the porous scaffolds. The identification and morphology of HA nanofibers were determined by X-ray diffraction and transmission electron microscopy, respectively. Scanning electron microscopy was used to examine the morphology of porous scaffolds and fracture surfaces to reveal the dominant toughening mechanisms. The results showed that the mechanical property of the scaffold was significantly enhanced by the inclusion of HA nanofibers. The porous composite scaffold attained a compressive strength of 9.8 +/- 0.3 MPa, comparable to the high-end value (2-10 MPa) of cancellous bone. The toughness of the scaffold increased from 1.00+/-0.04 to 1.72+/-0.02 kN/m, as the concentration of HA nanofibers increased from 0 to 5 wt %.     

Biocompatibility and osteogenicity of degradable Ca-deficient hydroxyapatite scaffolds from calcium phosphate cement for bone tissue engineering

Ca-deficient hydroxyapatite (CDHA) porous scaffolds were successfully fabricated from calcium phosphate cement (CPC) by a particle-leaching method. The morphology, porosity and mechanical strength as well as degradation of the scaffolds were characterized. The results showed that the CDHA scaffolds with a porosity of 81% showed open macropores with pore sizes of 400-500mum. Thirty-six per cent of these CDHA scaffolds were degraded after 12 weeks in Tris-HCl solution. Mesenchymal stem cells (MSCs) were cultured, expanded and seeded on the scaffolds, and the proliferation and differentiation of MSCs into osteoblastic phenotype were determined using MTT assay, alkaline phosphatase activity and scanning electron microscopy. The results revealed that the CDHA scaffolds were biocompatible and had no negative effects on the MSCs in vitro. The in vivo biocompatibility and osteogenicity of the scaffolds were investigated. Both CDHA scaffolds and MSC/scaffold constructs were implanted in rabbit mandibles and studied histologically. The results showed that CDHA scaffolds exhibited good biocompatibility and osteoconductivity. Moreover, the introduction of MSCs into the scaffolds dramatically enhanced the efficiency of new bone formation, especially at the initial stage after implantation (from 2 to 4 weeks). However, the CDHA scaffolds showed as good biocompatibility and osteogenicity as the hybrid ones at 8 weeks. These results indicate that the CDHA scaffolds fulfill the basic requirements of bone tissue engineering scaffold.     

In vitro evaluation of potential calcium phosphate scaffolds for tissue engineering

Nanocrystalline calcium phosphates are very interesting candidates as scaffolds for bone tissue engineering. These materials show excellent in vivo biocompatibility, cell proliferation, and resorption. In this work we have studied the osteoblast-like cell behavior seeded onto HA and BCP synthesized by controlled crystallization method and treated at different temperatures. In vitro cell attachment, proliferation, differentiation, spreading, and cytotoxicity tests have been carried out. The results can be explained as a function of the phase composition and microstructure. Under in vitro closed conditions, nanocrystalline HA depletes the calcium of the medium avoiding cell proliferation, whereas well-crystallized HA enhances high cell proliferation. On the other hand, nanocrystalline BCPs supply Ca(2+) to the medium due to the higher solubility of the beta-TCP component, allowing an excellent in vitro cellular response when osteoblast-like cells are seeded on it. These features make BCPs excellent candidates as scaffolds for bone tissue engineering.     

Direct deposited porous scaffolds of calcium phosphate cement with alginate for drug delivery and bone tissue engineering

This study reports the preparation of novel porous scaffolds of calcium phosphate cement (CPC) combined with alginate, and their potential usefulness as a three-dimensional (3-D) matrix for drug delivery and tissue engineering of bone. An α-tricalcium phosphate-based powder was mixed with sodium alginate solution and then directly injected into a fibrous structure in a Ca-containing bath. A rapid hardening reaction of the alginate with Ca(2+) helps to shape the composite into a fibrous form with diameters of hundreds of micrometers, and subsequent pressing in a mold allows the formation of 3-D porous scaffolds with different porosity levels. After transformation of the CPC into a calcium-deficient hydroxyapatite phase in simulated biological fluid the scaffold was shown to retain its mechanical stability. During the process biological proteins, such as bovine serum albumin and lysozyme, used as model proteins, were observed to be effectively loaded onto and released from the scaffolds for up to more than a month, proving the efficacy of the scaffolds as a drug delivering matrix. Mesenchymal stem cells (MSCs) were isolated from rat bone marrow and then cultured on the CPC-alginate porous scaffolds to investigate the ability to support proliferation of cells and their subsequent differentiation along the osteogenic lineage. It was shown that MSCs increasingly actively populated and also permeated into the porous network with time of culture. In particular, cells cultured within a scaffold with a relatively high porosity level showed favorable proliferation and osteogenic differentiation. An in vivo pilot study of the CPC-alginate porous scaffolds after implantation into the rat calvarium for 6 weeks revealed the formation of new bone tissue within the scaffold, closing the defect almost completely. Based on these results, the newly developed CPC-alginate porous scaffolds could be potentially useful as a 3-D matrix for drug delivery and tissue engineering of bone.     

Printability of calcium phosphate powders for three-dimensional printing of tissue engineering scaffolds

Three-dimensional printing (3DP) is a versatile method to produce scaffolds for tissue engineering. In 3DP the solid is created by the reaction of a liquid selectively sprayed onto a powder bed. Despite the importance of the powder properties, there has to date been a relatively poor understanding of the relation between the powder properties and the printing outcome. This article aims at improving this understanding by looking at the link between key powder parameters (particle size, flowability, roughness, wettability) and printing accuracy. These powder parameters are determined as key factors with a predictive value for the final 3DP outcome. Promising results can be expected for mean particle size in the range of 20-35 μm, compaction rate in the range of 1.3-1.4, flowability in the range of 5-7 and powder bed surface roughness of 10-25 μm. Finally, possible steps and strategies in pushing the physical limits concerning improved quality in 3DP are addressed and discussed.     

Perfusion electrodeposition of calcium phosphate on additive manufactured titanium scaffolds for bone engineering

A perfusion electrodeposition (P-ELD) system was reported to functionalize additive manufactured Ti6Al4V scaffolds with a calcium phosphate (CaP) coating in a controlled and reproducible manner. The effects and interactions of four main process parameters - current density (I), deposition time (t), flow rate (f) and process temperature (T) - on the properties of the CaP coating were investigated. The results showed a direct relation between the parameters and the deposited CaP mass, with a significant effect for t (P=0.001) and t-f interaction (P=0.019). Computational fluid dynamic analysis showed a relatively low electrolyte velocity within the struts and a high velocity in the open areas within the P-ELD chamber, which were not influenced by a change in f. This is beneficial for promoting a controlled CaP deposition and hydrogen gas removal. Optimization studies showed that a minimum t of 6 h was needed to obtain complete coating of the scaffold regardless of I, and the thickness was increased by increasing I and t. Energy-dispersive X-ray and X-ray diffraction analysis confirmed the deposition of highly crystalline synthetic carbonated hydroxyapatite under all conditions (Ca/P ratio=1.41). High cell viability and cell-material interactions were demonstrated by in vitro culture of human periosteum derived cells on coated scaffolds. This study showed that P-ELD provides a technological tool to functionalize complex scaffold structures with a biocompatible CaP layer that has controlled and reproducible physicochemical properties suitable for bone engineering.     

Synthesis and characterization of macroporous chitosan/calcium phosphate composite scaffolds for tissue engineering

Chitosan scaffolds reinforced by beta-tricalcium phosphate (beta-TCP) and calcium phosphate invert glass were fabricated with a low-cost, bioclean freeze-drying technique via thermally induced phase separation. The microstructure, mechanical performance, biodegradation, and bioactivity of the scaffolds were studied. The composite scaffolds were macroporous, and the pore structures of the scaffolds with beta-TCP and the glass appeared very different. Both the compressive modulus and yield strength of the scaffolds were greatly improved, and reinforced microstructures were achieved. The bioactivity tests showed a continuous decrease in both Ca and P concentrations of a simulated body fluid (SBF) after the scaffolds with beta-TCP were immersed in the SBF for more than 20 h, which suggests that an apatite layer might be formed on the scaffolds. However, the same was not observed for the pure chitosan scaffolds or the scaffolds incorporated with the glass. This was further confirmed by micrographs from scanning electron microscopy. This study suggests that the desirable pore structure, biodegradation rate, and bioactivity of the composite scaffolds might be achieved through controlling the ratio of chitosan and calcium phosphates or beta-TCP and the glass.     

Acidic peptide hydrogel scaffolds enhance calcium phosphate mineral turnover into bone tissue

Designed peptides may generate molecular scaffolds in the form of hydrogels to support tissue regeneration. We studied the effect of hydrogels comprising β-sheet-forming peptides rich in aspartic amino acids and of tricalcium phosphate (β-TCP)-loaded hydrogels on calcium adsorption and cell culture in vitro, and on bone regeneration in vivo. The hydrogels were found to act as efficient depots for calcium ions, and to induce osteoblast differentiation in vitro. In vivo studies on bone defect healing in rat distal femurs analyzed by microcomputerized tomography showed that the peptide hydrogel itself induced better bone regeneration in comparison to non-treated defects. A stronger regeneration capacity was obtained in bone defects treated with β-TCP-loaded hydrogels, indicating that the peptide hydrogels and the mineral act synergistically to enhance bone regeneration. In vivo regeneration was found to be better with hydrogels loaded with porous β-TCP than with hydrogels loaded with non-porous mineral. It is concluded that biocompatible and biodegradable matrices, rich in anionic moieties that efficiently adsorb calcium ions while supporting cellular osteogenic activity, may efficiently promote β-TCP turnover into bone mineral.     

双相钙磷生物陶瓷/硫酸钙骨水泥多孔三维支架的生物性能

背景：随着组织工程技术的发展,多孔生物陶瓷被越来越多的运用到骨缺损的修复中,当前的研究主要集中在这种生物陶瓷的合成及其各项性能的评价。 目的：研究一种新型骨水泥的制备方法并测定其理化性能及与成骨细胞的生物相容性。 方法：共沉淀法制备双相钙磷生物陶瓷粉体,利用胶体团聚成颗粒,烧结后得到颗粒状、多孔羟基磷灰石/磷酸三钙生物陶瓷,并按不同比例与高纯度医用半水硫酸钙混合制备钙磷陶瓷/硫酸钙骨水泥。 结果与结论：X射线衍射证实合成物质为双相钙磷陶瓷,颗粒状双相钙磷陶瓷具有多孔网状结构,骨水泥在   3 min内保持可塑状态,固化时间为15 min,固化温度为36.5 ℃,压缩强度最高为5.82 MPa,MTT毒性级为0级,成骨细胞在材料表面生长良好。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：