Complete ECM gene array table.

Hyaluronic acid (HA) is ubiquitously found in biological tissues and mediates wound healing mechanisms after injury by promoting cell migration and proliferation. With the development of tissue-engineered neural therapeutics, including off-the-shelf grafts for peripheral nerve repair, HA is an attractive material for clinical use because of its various biological roles. HA-based biomaterials have been carefully engineered to elicit specific in vivo host responses, however an important design feature that should be considered in these scaffolds is endogenous degradation. Hyaluronidases (HYALs) are the complementary enzymes that are responsible for HA turnover. Although HYAL expression has been widely characterized in various tissues, including the central nervous system, and for different pathologies, there remains a lack of knowledge of HYAL mediated turnover in peripheral nerve tissue. In this work, gene expression of two hyaluronidases, HYAL1 and HYAL2, and HA-binding receptor, CD44, were studied in two injury models: rat sciatic nerve crush and critical gap transection. HYAL2 and CD44 were shown to be upregulated 3 days after crush injury, whereas HYAL1 was upregulated at 3 weeks, which collectively demonstrate temporal patterning of HA breakdown. Additionally, differences were observed between HYAL and HA expression at 3 weeks when compared for both nerve injury models. The activity of HYAL in peripheral nerve tissue was determined to be approximately 0.11 μmol/min, which could be used to further model HA-based biomaterial breakdown for peripheral nerve applications. Overall, this work provides a landscape of HA turnover in peripheral nerve that can be used for future neural applications.

透明质酸（Hyaluronic acid, HA）广泛分布于生物组织中，可通过促进细胞迁移与增殖，介导损伤后的伤口愈合进程。随着组织工程化神经治疗技术的发展，包括用于外周神经修复的现成移植体，透明质酸凭借其多样的生物学功能，成为极具临床应用潜力的医用材料。尽管透明质酸基生物材料已通过精心工程化设计以诱导特定的体内宿主应答，但这类组织工程支架的一项关键设计考量因素为内源性降解特性。透明质酸酶（Hyaluronidases, HYALs）是负责透明质酸代谢周转的互补性酶类。尽管目前已在包括中枢神经系统在内的多种组织以及不同病理状态下，对透明质酸酶的表达完成了广泛表征，但针对外周神经组织中透明质酸酶介导的代谢周转，目前仍缺乏系统认知。本研究针对两种神经损伤模型——大鼠坐骨神经压榨损伤模型与临界间隙切断损伤模型，探究了两种透明质酸酶HYAL1、HYAL2以及透明质酸结合受体CD44的基因表达水平。研究结果显示，压榨损伤后3天，HYAL2与CD44的表达即出现上调，而HYAL1的表达上调则发生于损伤后3周，上述现象共同揭示了透明质酸降解的时序调控模式。此外，对比两种神经损伤模型，在损伤后3周时可观察到透明质酸酶与透明质酸的表达存在显著差异。经测定，外周神经组织中透明质酸酶的活性约为0.11 μmol/min，该数据可用于进一步构建适配外周神经应用的透明质酸基生物材料降解模型。综上，本研究全面刻画了外周神经组织中透明质酸的代谢周转全貌，可为未来神经领域的相关应用提供重要参考。