Department of Veterans Affairs, Atlanta VA Medical Center, Decatur, Georgia, USA.
Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA.
J Tissue Eng Regen Med. 2022 Dec;16(12):1138-1148. doi: 10.1002/term.3352. Epub 2022 Sep 30.
Articular cartilage injuries have a limited healing capacity and, due to inflammatory and catabolic activities, often experience progressive degeneration towards osteoarthritis. Current repair techniques generally provide short-term symptomatic relief; however, the regeneration of hyaline cartilage remains elusive, leaving both the repair tissue and surrounding healthy tissue susceptible to long-term wear. Therefore, methods to preserve cartilage following injury, especially from matrix loss and catabolism, are needed to delay, or even prevent, the deteriorative process. The goal of this study was to develop and evaluate a cartilage-penetrating hyaluronic-acid (HA) hydrogel to improve damaged cartilage biomechanics and prevent tissue degeneration. At time zero, the HA-based hydrogel provided a 46.5% increase in compressive modulus and a decrease in permeability after simulated degeneration of explants (collagenase application). Next, in a degenerative culture model (interleukin-1β [IL-1β] for 2 weeks), hydrogel application prior to or midway through the culture mitigated detrimental changes to compressive modulus and permeability observed in non-treated explants. Furthermore, localized loss of proteoglycan was observed in degenerative culture conditions alone (non-treated), but hydrogel administration significantly improved the retention of matrix elements. Finally, NITEGE staining and gene expression analysis showed the ability of the HA gel to decrease chondrocyte catabolic activity. These results highlight the importance of reinforcing damaged cartilage with a biomaterial system to both preserve tissue content and reduce catabolism associated with injury and inflammation.
关节软骨损伤的愈合能力有限，并且由于炎症和分解代谢活动，经常会朝着骨关节炎的方向发生进行性退化。目前的修复技术通常只能提供短期的症状缓解；然而，透明软骨的再生仍然难以实现，这使得修复组织和周围的健康组织都容易受到长期磨损的影响。因此，需要在受伤后（尤其是基质丢失和分解代谢）保留软骨的方法，以延迟甚至预防退化过程。本研究的目的是开发和评估一种可穿透软骨的透明质酸（HA）水凝胶，以改善受损软骨的生物力学性能并预防组织退化。在零时，基于 HA 的水凝胶在模拟的外植体退化（胶原酶应用）后提供了 46.5%的压缩模量增加和渗透性降低。接下来，在退行性培养模型（白细胞介素-1β [IL-1β] 培养 2 周）中，在培养前或中途应用水凝胶可以减轻未经处理的外植体中观察到的压缩模量和渗透性的不利变化。此外，仅在退行性培养条件下（未经处理）观察到蛋白聚糖的局部丢失，但水凝胶给药显著改善了基质成分的保留。最后，NITEGE 染色和基因表达分析表明，HA 凝胶能够降低软骨细胞的分解代谢活性。这些结果强调了用生物材料系统强化受损软骨的重要性，以保留组织含量并减少与损伤和炎症相关的分解代谢。
