Smart Healthcare, Interdisciplinary Research Division, Indian Institute of Technology-Jodhpur, NH 62, Surpura Bypass Road, Karwar, Rajasthan 342030, India.
Department of Bioscience & Bioengineering, Indian Institute of Technology-Jodhpur, NH 62, Surpura Bypass Road, Karwar, Rajasthan 342030, India.
ACS Appl Mater Interfaces. 2024 Jun 19;16(24):30929-30957. doi: 10.1021/acsami.4c05559. Epub 2024 Jun 4.
Bioengineered composite hydrogel platforms made of a supramolecular coassembly have recently garnered significant attention as promising biomaterial-based healthcare therapeutics. The mechanical durability of amyloids, in conjunction with the structured charged framework rendered by biologically abundant key ECM component glycosaminoglycan, enables us to design minimalistic customized biomaterial suited for stimuli responsive therapy. In this study, by harnessing the heparin sulfate-binding aptitude of amyloid fibrils, we have constructed a pH-responsive extracellular matrix (ECM) mimicking hydrogel matrix. This effective biocompatible platform comprising heparin sulfate-amyloid coassembled hydrogel embedded with polyphenol functionalized silver nanoparticles not only provide a native skin ECM-like conductive environment but also provide wound-microenvironment responsive on-demand superior antibacterial efficacy for effective diabetic wound healing. Interestingly, both the cytocompatibility and antibacterial properties of this bioinspired matrix can be fine-tuned by controlling the mutual ratio of heparin sulfate-amyloid and incubated silver nanoparticle components, respectively. The designed biomaterial platform exhibits notable effectiveness in the treatment of chronic hyperglycemic wounds infected with multidrug-resistant bacteria, because of the integration of pH-responsive release characteristics of the incubated functionalized AgNP and the antibacterial amyloid fibrils. In addition to this, the aforementioned assemblage shows exceptional hemocompatibility with significant antibiofilm and antioxidant characteristics. Histological evidence of the incised skin tissue sections indicates that the fabricated composite hydrogel is also effective in controlling pro-inflammatory cytokines such as IL6 and TNFα expressions at the wound vicinity with significant upregulation of angiogenesis markers like CD31 and α-SMA.
由超分子共组装制成的生物工程复合水凝胶平台最近作为有前途的基于生物材料的医疗治疗方法引起了极大的关注。淀粉样蛋白的机械耐久性，结合生物丰富的关键细胞外基质成分糖胺聚糖提供的结构化带电框架，使我们能够设计极简定制的生物材料，适合刺激响应治疗。在这项研究中，我们利用淀粉样纤维的肝素硫酸结合能力，构建了一种 pH 响应的细胞外基质（ECM）模拟水凝胶基质。这种有效的生物相容性平台由肝素硫酸-淀粉样共组装水凝胶组成，其中嵌入了多酚功能化的银纳米粒子，不仅提供了类似于天然皮肤 ECM 的导电环境，而且还提供了对伤口微环境的响应，按需提供卓越的抗菌功效，以有效治疗糖尿病伤口。有趣的是，通过分别控制肝素硫酸-淀粉样和孵育银纳米粒子成分的相互比例，可以调整这种仿生基质的细胞相容性和抗菌性能。由于孵育的功能化 AgNP 和抗菌淀粉样纤维的 pH 响应释放特性的整合，所设计的生物材料平台在治疗感染多药耐药菌的慢性高血糖伤口方面表现出显著的效果。此外，上述组合还表现出出色的血液相容性，具有显著的抗生物膜和抗氧化特性。切口皮肤组织切片的组织学证据表明，所制备的复合水凝胶还可以有效控制伤口附近促炎细胞因子（如 IL6 和 TNFα）的表达，并显著上调血管生成标志物（如 CD31 和 α-SMA）。
