Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, United States.
Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, United States.
Acta Biomater. 2024 Sep 15;186:246-259. doi: 10.1016/j.actbio.2024.07.057. Epub 2024 Aug 5.
Bioresorbable shape memory polymers (SMP) are an emerging class of polymers that can help address several challenges associated with minimally invasive surgery by providing a solution for structural tissue repair. Like most synthetic polymer networks, SMPs require additional biorelevance and modification for biomedical applications. Methodologies used to incorporate bioactive ligands must preserve SMP thermomechanics and ensure biofunctionality following in vivo delivery. We have previously described the development of a novel thermoresponsive bioresorbable SMP, poly (glycerol dodecanedioate) (PGD). In this study, cell-adhesive peptide sequences RGD and YIGSR were conjugated with PGD. We investigated 1) the impact of conjugated peptides on the fixity (R), recovery (R), and recovery rate (dR/dT), 2) the impact of conjugated peptides on cell binding, and 3) the impact of the shape memory cycle (T) on conjugated peptide functionality towards binding human bone marrow stromal cells (BMSC). Peptide conjugation conditions impact fixity but not the recovery or recovery rate (p < 0.01). Peptide-conjugated substrates increased cell attachment and proliferation compared with controls (p < 0.001). Using complementary integrin binding cell-adhesive peptides increased proliferation compared with using single peptides (p < 0.05). Peptides bound to PGD substrates exhibited specificity to their respective integrin targets. Following the shape memory cycle, peptides maintained functionality and specificity depending on the shape memory cycle conditions (p < 0.001). The dissipation of strain energy during recovery can drive differential arrangement of conjugated sequences impacting functionality, an important design consideration for functionalized SMPs. STATEMENT OF SIGNIFICANCE: Shape memory elastomers are an emerging class of polymers that are well-suited for minimally invasive repair of soft tissues. Tissue engineering approaches commonly utilize biodegradable scaffolds to deliver instructive cues, including cells and bioactive signals. Delivering these instructive cues on biodegradable shape memory elastomers requires modification with bioactive ligands. Furthermore, it is necessary to ensure the specificity of the ligands to their biological targets when conjugated to the polymer. Moreover, the bioactive ligand functionality must be conserved after completing the shape memory cycle, for applications in tissue engineering.
生物可吸收形状记忆聚合物（SMP）是一类新兴聚合物，通过为结构性组织修复提供解决方案，可以帮助解决微创手术相关的多个挑战。与大多数合成聚合物网络一样，SMP 在用于生物医学应用时需要额外的生物相关性和修饰。用于结合生物活性配体的方法必须保留 SMP 的热机械性能，并确保在体内输送后保持生物功能性。我们之前已经描述了一种新型热响应型生物可吸收 SMP，聚（十二烷二酸甘油酯）（PGD）的开发。在这项研究中，细胞黏附肽序列 RGD 和 YIGSR 与 PGD 相共轭。我们研究了 1） 共轭肽对固定性（R）、回复性（R）和回复速率（dR/dT）的影响，2） 共轭肽对细胞结合的影响，以及 3） 形状记忆循环（T）对结合人骨髓基质细胞（BMSC）的共轭肽功能的影响。肽共轭条件会影响固定性，但不影响回复性或回复速率（p < 0.01）。与对照相比，肽偶联基底增加了细胞附着和增殖（p < 0.001）。与使用单一肽相比，使用互补整合素结合的细胞黏附肽可增加增殖（p < 0.05）。肽结合到 PGD 基底上表现出对各自整合素靶标的特异性。在形状记忆循环之后，根据形状记忆循环条件，肽保持其功能和特异性（p < 0.001）。在回复过程中应变能的耗散可以驱动共轭序列的差异排列，从而影响功能，这是功能化 SMP 的一个重要设计考虑因素。研究意义：形状记忆弹性体是一类新兴聚合物，非常适合微创修复软组织。组织工程方法通常利用可生物降解的支架来提供包括细胞和生物活性信号在内的指令性线索。在可生物降解的形状记忆弹性体上递送这些指令性线索需要用生物活性配体进行修饰。此外，当与聚合物偶联时，有必要确保配体对其生物靶标的特异性。此外，在完成形状记忆循环后，生物活性配体的功能必须保持不变，以便在组织工程中应用。
