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Photocrosslinkable hydrogels as cell-scaffolds for tissue engineering cartilage: A study examining gel properties, degradation, mechanical loading and clinical relevance.

机译：可光交联的水凝胶作为组织工程软骨的细胞支架：一项研究凝胶性质，降解，机械负荷和临床相关性的研究。

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Cartilage, unlike other tissues, has a limited ability for self-repair. Therefore, approaches to engineer cartilage through the development of cell-carriers are important. We are particularly interested in using photopolymerizable hydrogels as a chondrocyte-carrier. Photopolymerization is desirable because the scaffold can be formed in situ at physiological conditions with temporal and spatial control over the polymerization. In designing an in situ forming cell-scaffold, the scaffold should promote cell proliferation and tissue secretion, span the thickness of native cartilage, restore function initially, degrade at a similar rate to tissue formation, transfer mechanical signals to the cells, and integrate into the surrounding tissue. This thesis tests the hypothesis that photocrosslinked hydrogels will meet these design requirements for a suitable chondrocyte-carrier to engineer cartilage.; To test this hypothesis, photocrosslinked hydrogels based on poly(ethylene glycol) were employed as a model system. Using these gels, we have shown that chondrocytes survive the photoencapsulation process, remaining viable and functional, particularly in hydrogels that span the thickness of native cartilage and exhibit similar properties to the native tissue. The spatial distribution of secreted extracellular matrix (ECM) molecules was closely related to the crosslinking density (ρx) of the hydrogel and was controlled by incorporating degradable crosslinks into the hydrogel.; This knowledge was expanded into developing multivinyl macromers derived from natural components found in cartilage (negatively charged chondroitin sulfate) and from poly(vinyl alcohol) to design hydrogels that mimic the native tissue and to gain additional control over the gel macroscopic properties and degradation times. Interestingly, the ECM composition depended on the gel chemistry.; This research has also aimed to address issues associated with in situ formed cell-carriers, such as mechanical loading and clinical concerns. Mechanical loading influenced cell morphology and cell function in a ρx-dependent manner. From a clinical perspective, in situ polymerization was shown to improve initial adhesion of the gel to the adjacent cartilage, and the neocartilaginous tissue integrated into the surrounding native tissue.; In summary, photocrosslinked hydrogels are promising cell-carriers that can be in situ polymerized into any shaped defect, and the 3-D gel environment promotes the formation of a functional tissue rich in cartilage-like ECM components, facilitating integrative repair.
机译：与其他组织不同，软骨的自我修复能力有限。因此，通过细胞载体的发育来工程化软骨的方法很重要。我们对使用可光聚合的水凝胶作为软骨细胞载体特别感兴趣。光聚合是合乎需要的，因为支架可以在生理条件下通过聚合的时间和空间控制就地形成。在设计原位形成细胞支架时，支架应促进细胞增殖和组织分泌，跨越天然软骨的厚度，最初恢复功能，以与组织形成相似的速率降解，传递机械信号进入细胞，并整合到周围组织中。本论文检验了光交联水凝胶将满足这些设计要求的合适软骨细胞载体工程化软骨的假设。为了验证这一假设，将基于聚乙二醇的光交联水凝胶用作模型系统。使用这些凝胶，我们已经显示，软骨细胞在光囊化过程中幸存下来，保持活力和功能，特别是在跨越天然软骨厚度并表现出与天然组织相似性质的水凝胶中。分泌的细胞外基质（ECM）分子的空间分布与水凝胶的交联密度（ρ x ）密切相关，并通过将可降解的交联结合到水凝胶中来控制。该知识被扩展到开发由软骨（带负电的硫酸软骨素）中的天然成分和聚乙烯醇制得的聚乙烯基大分子单体，以设计模仿天然组织的水凝胶，并获得对凝胶宏观特性和降解时间的额外控制。有趣的是，ECM的组成取决于凝胶的化学性质。这项研究还旨在解决与原位形成的细胞载体相关的问题，例如机械负荷和临床问题。机械载荷以依赖于ρ x 的方式影响细胞形态和细胞功能。从临床角度来看，显示原位聚合可改善凝胶与相邻软骨的初始粘附，并使新软骨组织整合到周围的天然组织中。总之，光交联的水凝胶是有希望的细胞载体，可以被就地聚合成任何形状的缺陷，并且3-D凝胶环境促进了富含软骨样ECM成分的功能组织的形成，促进整体维修。

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