Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, Connecticut, USA.
Department of Orthopaedic Surgery, UConn Health, Farmington, Connecticut, USA.
J Biomed Mater Res A. 2021 Nov;109(11):2137-2153. doi: 10.1002/jbm.a.37200. Epub 2021 May 11.
Whereas synthetic biodegradable polymers have been successfully applied for the delivery of biologics in other tissues, the anatomical complexity, poor blood supply, and reduced clearance of degradation byproducts in the rotator cuff create unique design challenges for implantable biomaterials. Here, we investigated lower molecular weight poly-lactic acid co-epsilon-caprolactone (PLA-CL) formulations with varying molecular weight and film casting concentrations as potential matrices for the therapeutic delivery of biologics in the rotator cuff. Matrices were fabricated with target footprint dimensions to facilitate controlled and protected release of model biologic (Bovine Serum Albumin), and anatomically-unhindered implantation under the acromion in a rodent model of acute rotator cuff repair. The matrix obtained from the highest polymeric-film casting concentration showed a controlled release of model biologics payload. The tested matrices rapidly degraded during the initial 4 weeks due to preferential hydrolysis of the lactide-rich regions within the polymer, and subsequently maintained a stable molecular weight due to the emergence of highly-crystalline caprolactone-rich regions. pH evaluation in the interior of the matrix showed minimal change signifying lesser accumulation of acidic degradation byproducts than seen in other bulk-degrading polymers, and maintenance of conformational stability of the model biologic payload. The context-dependent biocompatibility evaluation in a rodent model of acute rotator cuff repair showed matrix remodeling without eliciting excessive inflammatory reaction and is anticipated to completely degrade within 6 months. The engineered PLA-CL matrices offer unique advantages in controlled and protected biologic delivery, non-toxic biodegradation, and biocompatibility overcoming several limitations of commonly-used biodegradable polyesters.
尽管合成可生物降解聚合物已成功应用于其他组织中生物制剂的递送，但肩袖解剖结构复杂、血液供应不良以及降解副产物清除率降低，为可植入生物材料的设计带来了独特的挑战。在这里，我们研究了不同分子量的低分子量聚乳酸共 ε-己内酯（PLA-CL）配方，以及不同分子量和薄膜铸造浓度的配方，将其作为在肩袖中治疗性递送生物制剂的潜在基质。这些基质的制造尺寸与目标足迹相匹配，以促进模型生物制剂（牛血清白蛋白）的受控和保护释放，并在急性肩袖修复的啮齿动物模型中在肩峰下进行解剖无障碍植入。从最高聚合物薄膜铸造浓度获得的基质显示出模型生物制剂有效负载的控制释放。由于聚合物中内消旋乳酸丰富区域的优先水解，测试的基质在最初的 4 周内迅速降解，随后由于高度结晶的己内酯丰富区域的出现，分子量保持稳定。对基质内部 pH 值的评估表明，酸性降解副产物的积累较少，与其他大量降解聚合物相比，这表明其较少的积累，并且模型生物制剂有效负载的构象稳定性得以维持。在急性肩袖修复的啮齿动物模型中进行的上下文相关的生物相容性评估表明，基质重塑而不会引起过度的炎症反应，预计其将在 6 个月内完全降解。工程 PLA-CL 基质在控制和保护生物制剂递送、无毒生物降解和生物相容性方面具有独特的优势，克服了常用可生物降解聚酯的几种局限性。
