Biodegradable and elastic flock scaffolds from a single material system based on chitosan for articular cartilage regeneration

本课题的目的是从单一材料系统中开发出一种可生物降解的、机械稳定的弹性植绒支架，并对其作为组织工程软骨三维载体结构的应用进行系统的细胞生物学研究。为此，将开发一种可重复的纺丝工艺，用于描绘具有定义的生物功能和适用于纺织加工的特性的纯壳聚糖长丝纱线。将开发一种壳聚糖膜和一种新型超轻表面结构壳聚糖织物作为基底（载体材料）。采用一种新型的壳聚糖胶粘剂将植绒纤维与基材粘合在一起。为了保证新型静电植绒用壳聚糖植绒纤维的导电性能，合成了具有生物相容性的制备配方。一个完全可生物降解的植绒支架，这是作为一个单一的材料系统的基础上壳聚糖作为基板，植绒纤维和粘合剂，是通过有针对性的配置的每个组件的植绒过程中产生的。关于支架的医疗应用的高要求需要封闭的工艺链。这将导致限定的、可缩放的孔径（优选110-150 μm），并且同时通过最小的材料需求而导致支架的高尺寸稳定性。结构的各向异性形态保证了机械强度、弹性和高孔隙率。所有组件的生物相容性均通过细胞培养研究证明。通过体外试验对实际工作状态进行连续、合格的评估，并规范有关材料和结构的要求，作为目标技术和结构开发的基础。此外，还将研究细胞培养条件下植绒支架的稳定性及其降解行为。将人原代软骨细胞（hCh）和人间充质干细胞（hMSC）接种到可生物降解的植绒支架上并分析其软骨分化，证明了各向异性孔形态对细胞行为的影响。将通过产生用于在可生物降解的植绒支架上培养hCh/hMSC的合适的生物聚合物凝胶来开发这些开放多孔支架的细胞接种的有效方法。在另外的实验中，将研究周期性机械载荷对在植绒支架中培养的细胞的基质合成和成软骨分化的影响，这将为关节软骨缺损的新疗法提供基础。

The aim of this project is the development of a biodegradable and mechanically stable elastic flock scaffold from a single material system with adjustable parameters based on chitosan as well as the systematic cell biological investigation in regard to its application as three-dimensional carrier structure for tissue engineering of articular cartilage. For this a reproducible spin process for depiction of filament yarns from pure chitosan with defined biological function and properties suitable for textile processing will be developed. Both a chitosan membrane and a novel ultra light surface structured chitosan woven fabric will be developed as substrate (carrier material). A novel adhesive based on chitosan, is applied to join the flock fibers with the substrate. In order to guarantee the electrical conductivity of novel chitosan flock fibers for electrostatic flocking, biocompatible recipe for preparation will be synthesized. A completely biodegradable flock scaffold, which is available as a single material system based on chitosan as substrate, flock fiber and adhesive, is generated by targeted configuration of each component of the flock process. The high demands concerning medical application of the scaffolds require a closed process chain. This will lead to a defined, scalable pore size (preferably 110-150 µm) and simultaneously to a high dimension stability of the scaffolds by minimum material requisition. The anisotropic morphology of the constructs guarantees both mechanical strength, elasticity and a high porosity at the same time.The biocompatibility of all components is proved by cell culture investigations. A continuous and qualified evaluation of the actual work state and a specification of requirements concerning the materials and structures as a fundament for targeted technology and structure development is carried out by means of in vitro tests. Also stability of the flock scaffolds under cell culture conditions and their degradation behavior will e studied. Seeding of biodegradable flock scaffolds with human primary chondrocytes (hCh) and human mesenchymal stem cells (hMSC) and analysis of their chondrogenic differentiation demonstrate the effects of anisotropic pore morphology on the cell behavior. An effective method of cell seeding of these open porous scaffolds will be developed by generating suited biopolymer gels for cultivation of hCh/hMSC on biodegradable flock scaffolds. In additional experiments the effect of cyclic mechanical loading on matrix synthesis and chondrogenic differentiation of cells cultivated in flock scaffolds will be investigated, which will provide the basis for a novel therapy of articular cartilage defects.