Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
J Mater Chem B. 2023 Jul 19;11(28):6621-6633. doi: 10.1039/d3tb00265a.
Tissue resorption and remodeling are pivotal steps in successful healing and regeneration, and it is important to design biomaterials that are responsive to regenerative processes in native tissue. The cell types responsible for remodeling, such as macrophages in the soft tissue wound environment and osteoclasts in the bone environment, utilize a class of enzymes called proteases to degrade the organic matrix. Many hydrophobic thermoplastics used in tissue regeneration are designed to degrade and resorb passively through hydrolytic mechanisms, leaving the potential of proteolytic-guided degradation underutilized. Here, we report the design and synthesis of a tyrosol-derived peptide-polyester block copolymer where protease-mediated resorption is tuned through changing the chemistry of the base polymer backbone and protease specificity is imparted through incorporation of specific peptide sequences. Quartz crystal microbalance was used to quantify polymer surface resorption upon exposure to various enzymes. Aqueous solubility of the diacids and the thermal properties of the resulting polymer had a significant effect on enzyme-mediated polymer resorption. While peptide incorporation at 2 mol% had little effect on the final thermal and physical properties of the block copolymers, its incorporation improved polymer resorption significantly in a peptide sequence- and protease-specific manner. To our knowledge, this is the first example of a peptide-incorporated linear thermoplastic with protease-specific sensitivity reported in the literature. The product is a modular system for engineering specificity in how polyesters can resorb under physiological conditions, thus providing a potential framework for improving vascularization and integration of biomaterials used in tissue engineering.
组织吸收和重塑是成功愈合和再生的关键步骤，设计对天然组织再生过程有响应的生物材料非常重要。负责重塑的细胞类型，如软组织伤口环境中的巨噬细胞和骨环境中的破骨细胞，利用一类称为蛋白酶的酶来降解有机基质。许多用于组织再生的疏水性热塑性塑料被设计为通过水解机制被动降解和吸收，从而未充分利用蛋白水解引导的降解的潜力。在这里，我们报告了一种酪氨酸衍生的肽-聚酯嵌段共聚物的设计和合成，其中通过改变基础聚合物主链的化学性质来调节蛋白酶介导的吸收，并且通过掺入特定的肽序列赋予蛋白酶特异性。石英晶体微天平用于量化暴露于各种酶时聚合物表面的吸收。二酸的水溶解度和所得聚合物的热性能对酶介导的聚合物吸收有很大影响。虽然在 2mol%的肽掺入对嵌段共聚物的最终热和物理性能几乎没有影响，但它以肽序列和蛋白酶特异性的方式显著改善了聚合物的吸收。据我们所知，这是文献中报道的第一个具有蛋白酶特异性敏感性的肽掺入线性热塑性塑料的实例。该产品是一种用于工程聚酯在生理条件下如何吸收的特异性的模块化系统，从而为改善用于组织工程的生物材料的血管化和整合提供了潜在框架。
