Gao Daqian, Shipman William D, Sun Yaping, Yang Weijun, Mathew Angelin Tresa, Beraki Leleda, Glahn Joshua Zev, Kochen Alejandro, Kyriakides Themis R, Horsley Valerie, Hsia Henry C
Division of Plastic Surgery, Department of Surgery, Yale School of Medicine, Yale University, 310 Cedar Street, New Haven, Connecticut 06510, United States.
VA Connecticut Healthcare, 950 Campbell Ave, West Haven, Connecticut 06516, United States.
ACS Appl Bio Mater. 2025 Feb 17;8(2):1675-1683. doi: 10.1021/acsabm.4c01853. Epub 2025 Jan 31.
Encapsulating fibroblasts in alginate hydrogels is a promising strategy to promote wound healing. However, improving the cell function within the alginate matrix remains a challenge. In this study, we engineer an injectable hydrogel through mixing alginate function with collagen and fibronectin, creating a better microenvironment for enhancing fibroblast function and cytokine secretion. We systematically analyze microstructure, mechanical properties, and fibroblast behavior of the developed hydrogel and compare it to alginate control. Our results demonstrate that inclusion collagen and fibronectin lead to the formation of fibrils on macroporous structures with pore sizes ranging from 100 to 500 μm. Compared to collagen hydrogel, the composite hydrogel shows approximately 12-fold increase in storage modulus. After encapsulating fibroblasts into the modified hydrogels, we observed increased fibroblast spreading, proliferation, and cytokine secretion when compared to neat alginate hydrogel. In addition, VEGF secretion of encapsulated fibroblasts is upregulated, indicating its pro-angiogenic potential. These findings suggest that the alginate/collagen/fibronectin hydrogel-encapsulated fibroblasts might serve as a promising therapeutic approach for wound healing.
将成纤维细胞包裹在海藻酸盐水凝胶中是促进伤口愈合的一种有前景的策略。然而,改善海藻酸盐基质内的细胞功能仍然是一项挑战。在本研究中,我们通过将海藻酸盐功能与胶原蛋白和纤连蛋白混合来设计一种可注射水凝胶,从而为增强成纤维细胞功能和细胞因子分泌创造更好的微环境。我们系统地分析了所开发水凝胶的微观结构、力学性能和成纤维细胞行为,并将其与海藻酸盐对照进行比较。我们的结果表明,加入胶原蛋白和纤连蛋白会导致在孔径为100至500μm的大孔结构上形成原纤维。与胶原蛋白水凝胶相比,复合水凝胶的储能模量增加了约12倍。将成纤维细胞封装到改性水凝胶中后,与纯海藻酸盐水凝胶相比,我们观察到成纤维细胞的铺展、增殖和细胞因子分泌增加。此外,封装的成纤维细胞的VEGF分泌上调,表明其具有促血管生成潜力。这些发现表明,海藻酸盐/胶原蛋白/纤连蛋白水凝胶封装的成纤维细胞可能是一种有前景的伤口愈合治疗方法。