Cartilage-penetrating hyaluronic acid hydrogel preserves tissue content and reduces chondrocyte catabolism
Cartilage-penetrating hyaluronic acid hydrogel preserves tissue content and reduces chondrocyte catabolism
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DOI：
10.1002/term.3352
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发表时间：
2022-09-30
影响因子：
3.3
通讯作者：
Patel, Jay M.
中科院分区：
文献类型：
--
作者：
Kowalski, Michael A.;Fernandes, Lorenzo M.;Patel, Jay M.
关节软骨损伤具有有限的愈合能力，并且由于炎症和分解代谢活动，经常经历向骨关节炎的进行性退化。目前的修复技术通常提供短期的症状缓解;然而，透明软骨的再生仍然难以捉摸，使修复组织和周围的健康组织容易受到长期磨损。因此，需要在损伤后保护软骨的方法，特别是防止基质损失和软骨炎，以延迟或甚至防止恶化过程。本研究的目的是开发和评估一种软骨穿透透明质酸（HA）水凝胶，以改善受损软骨的生物力学和防止组织变性。在零时，HA基水凝胶在外植体模拟变性（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，在变性培养模型（白细胞介素-1 β [IL-1 β]持续2周）中，在培养之前或培养中途应用水凝胶减轻了在未处理外植体中观察到的压缩模量和渗透性的有害变化。此外，仅在变性培养条件下（未处理）观察到蛋白聚糖的局部损失，但水凝胶给药显著改善了基质元素的保留。最后，NITEGE染色和基因表达分析显示HA凝胶降低软骨细胞分解代谢活性的能力。这些结果强调了用生物材料系统加固受损软骨的重要性，以保护组织内容物并减少与损伤和炎症相关的分解代谢。
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-1 beta [IL-1 beta] 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.