Biomimetic double network hydrogels of chondroitin sulfate and synthetic polypeptides for cartilage tissue engineering.

IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS
Juhi Singh, Jacob C Kadir, Jason D Orlando, Stefanie A Sydlik
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Abstract

Articular cartilage defects are common, and the progressive deterioration of cartilage frequently results in the onset of osteoarthritis. However, the intrinsic regenerative capacity of articular cartilage is minimal. Synthetic therapeutic solutions for treating cartilage damage are being developed. However, current scaffolds and hydrogels employed in cartilage tissue engineering face limitations in promoting cellular activity and providing sufficient load-bearing strength. This is primarily due to suboptimal crosslinking methods for the synthetic scaffolds composed of natural proteins and glycosaminoglycans (GAGs). Synthetic polypeptides, owing to their customizable reactive functional groups, present an exciting opportunity to enhance crosslinking through both physical and chemical approaches. This study introduces a strategy for the development of injectable, shape-adaptive double network hydrogels that closely replicate the structural integrity and mechanical properties of native cartilage. These hydrogels are composed of photocrosslinkable GAGs, specifically methacrylated chondroitin sulfate A (CSMA), combined with a synthetic polypeptide, poly(L-lysine) (PLL). By varying the degree of polymerization (DP) of PLL and weight percentage of PLL in the composition, the hydrogels can be optimized for desired material properties. Varying DP of PLLs varies the molecular weight between crosslinks, thus leading to tunable rigidity (yield strength, ultimate compression strength, storage modulus) and toughness. We further this tunability through the integration of photoresponsive components, enabling controlled, non-invasive post-injection modifications. Initial testing indicates that these double network hydrogels exhibit significantly improved mechanical strength compared to hydrogels formed solely from CSMA, positioning them as strong candidates for minimally invasive cartilage defect repair. This innovative method offers the potential to accelerate recovery, restore joint function, and improve patients' overall quality of life.

软骨组织工程用硫酸软骨素仿生双网水凝胶及合成多肽。
关节软骨缺损是常见的,软骨的进行性恶化经常导致骨关节炎的发作。然而,关节软骨的内在再生能力是最小的。用于治疗软骨损伤的合成治疗溶液正在开发中。然而,目前用于软骨组织工程的支架和水凝胶在促进细胞活性和提供足够的承载强度方面存在局限性。这主要是由于天然蛋白质和糖胺聚糖(GAGs)组成的合成支架的交联方法不理想。合成多肽由于其可定制的活性官能团,为通过物理和化学方法增强交联提供了令人兴奋的机会。本研究介绍了一种可注射的、自适应形状的双网络水凝胶的开发策略,这种水凝胶可以复制天然软骨的结构完整性和机械性能。这些水凝胶由可光交联的GAGs,特别是甲基丙烯酸硫酸软骨素A (CSMA),与合成的多肽聚l -赖氨酸(PLL)结合而成。通过改变聚乳酸的聚合度(DP)和聚乳酸在组合物中的重量百分比,可以优化水凝胶以达到所需的材料性能。pll的DP变化会改变交联之间的分子量,从而导致可调的刚度(屈服强度、极限压缩强度、存储模量)和韧性。我们通过光响应组件的集成进一步提高了这种可调性,实现了可控的、非侵入性的注射后修改。初步测试表明,与仅由CSMA形成的水凝胶相比,这些双网状水凝胶具有显著提高的机械强度,使其成为微创软骨缺损修复的有力候选者。这种创新的方法提供了加速恢复、恢复关节功能和提高患者整体生活质量的潜力。
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来源期刊
Biomaterials Science
Biomaterials Science MATERIALS SCIENCE, BIOMATERIALS-
CiteScore
11.50
自引率
4.50%
发文量
556
期刊介绍: Biomaterials Science is an international high impact journal exploring the science of biomaterials and their translation towards clinical use. Its scope encompasses new concepts in biomaterials design, studies into the interaction of biomaterials with the body, and the use of materials to answer fundamental biological questions.
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