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用于关节软骨组织工程的具有靶向降解特性的 3D 打印增强支架。

3D-Printed Reinforcement Scaffolds with Targeted Biodegradation Properties for the Tissue Engineering of Articular Cartilage.

机构信息

Institute for Biomechanics, Otto-Stern-Weg 7, ETH Zürich, Zürich, CH-8093, Switzerland.

Poly-Med Inc, 51 Technology Drive, Anderson, SC, 29625, USA.

出版信息

Adv Healthc Mater. 2021 Dec;10(23):e2101094. doi: 10.1002/adhm.202101094. Epub 2021 Oct 18.

Abstract

Achieving regeneration of articular cartilage is challenging due to the low healing capacity of the tissue. Appropriate selection of cell source, hydrogel, and scaffold materials are critical to obtain good integration and long-term stability of implants in native tissues. Specifically, biomechanical stability and in vivo integration can be improved if the rate of degradation of the scaffold material matches the stiffening of the sample by extracellular matrix secretion of the encapsulated cells. To this end, a novel 3D-printed lactide copolymer is presented as a reinforcement scaffold for an enzymatically crosslinked hyaluronic acid hydrogel. In this system, the biodegradable properties of the reinforced scaffold are matched to the matrix deposition of articular chondrocytes embedded in the hydrogel. The lactide reinforcement provides stability to the soft hydrogel in the early stages, allowing the composite to be directly implanted in vivo with no need for a preculture period. Compared to pure cellular hydrogels, maturation and matrix secretion remain unaffected by the reinforced scaffold. Furthermore, excellent biocompatibility and production of glycosaminoglycans and collagens are observed at all timepoints. Finally, in vivo subcutaneous implantation in nude mice shows cartilage-like tissue maturation, indicating the possibility for the use of these composite materials in one-step surgical procedures.

摘要

由于关节软骨的愈合能力较低,实现其再生极具挑战性。合适的细胞来源、水凝胶和支架材料的选择对于获得植入物在天然组织中的良好整合和长期稳定性至关重要。具体来说,如果支架材料的降解速率与包封细胞的细胞外基质分泌使样品变硬的速率相匹配,则可以提高生物力学稳定性和体内整合性。为此,提出了一种新型的 3D 打印丙交酯共聚物作为酶交联透明质酸水凝胶的增强支架。在该体系中,增强支架的可生物降解性能与嵌入水凝胶中的关节软骨细胞的基质沉积相匹配。丙交酯增强物为早期的软水凝胶提供了稳定性,使得复合材料无需预培养即可直接体内植入。与纯细胞水凝胶相比,增强支架对成熟和基质分泌没有影响。此外,在所有时间点都观察到良好的生物相容性和糖胺聚糖和胶原蛋白的产生。最后,在裸鼠的皮下体内植入表明软骨样组织成熟,表明这些复合材料在一步手术中使用的可能性。

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