Biomaterials and Multiscale Mechanics Lab, Department of Metallurgical and Materials Engineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India; Molecular Endocrinology Lab, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India; Centre of Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India.
Department of Pharmacy, Maharshi Markandeshwar University (Deemed to Be University), Mullana, Haryana 133207, India.
Biomater Adv. 2022 Aug;139:212980. doi: 10.1016/j.bioadv.2022.212980. Epub 2022 Jun 9.
Full-thickness wounds are difficult to heal spontaneously. Scaffolds, meant for treating full-thickness wounds, should ensure proper tissue regeneration, both structurally and functionally. An ideal scaffold should mimic the physical, mechanical and biochemical properties of natural skin. However, available mono- or bi-layer skin scaffolds lack in the precise architecture and functionality, thus, failing to provide scar-free regeneration of full-thickness skin wounds. These unmet challenges of scar-free skin regeneration have been addressed in the present study for the first time. This research deals with the synthesis of a low-cost, structurally and functionally graded single unit biodegradable polymeric scaffold. The functional gradient in this scaffold was achieved by varying polymer concentration and electrospinning parameters. This gradient in the scaffold provided the required microenvironment for proper functional and structural reconstruction of all the layers of natural skin. The mechanical property of the scaffold matched that of the natural skin. Besides, the degradation kinetics of the scaffold was in coordination with the regeneration time for the full-thickness wound. The porosity and hydrophilicity gradients of the scaffold helped it mimic the in vivo hypodermal, dermal and epidermal microenvironments of the skin, simultaneously. Co-culturing PCS-201 (dermal fibroblasts) and HaCaT (keratinocytes) on the scaffold resulted in successful regeneration through cellular proliferation, differentiation and organization of the skin tissue. The scaffold also displayed better wound healing in vivo, in terms of speedy wound closure and proper tissue regeneration, in comparison to the standard treatment. Altogether, this study successfully established a simple, one-step synthesis process of a functionally graded, bioresorbable scaffold for scar-free, native-like, structural and functional regeneration of full-thickness skin wounds. Due to cost-effectiveness, easy synthesis process and microarchitectural features, the designed scaffold possesses a potential of translation to a good commercial wound healing product.
全层创面难以自发愈合。用于治疗全层创面的支架应确保适当的组织再生，无论是在结构上还是功能上。理想的支架应模仿天然皮肤的物理、机械和生化特性。然而，现有的单层或双层皮肤支架在精确的结构和功能上存在不足，因此无法实现全层皮肤创面的无瘢痕再生。本研究首次针对无瘢痕皮肤再生的这些未满足的挑战进行了研究。本研究涉及一种低成本、结构和功能梯度的单一可生物降解聚合物支架的合成。该支架中的功能梯度通过改变聚合物浓度和静电纺丝参数来实现。支架中的这种梯度为天然皮肤所有层的适当功能和结构重建提供了所需的微环境。支架的机械性能与天然皮肤相匹配。此外，支架的降解动力学与全层创面的再生时间相协调。支架的孔隙率和亲水性梯度使其能够同时模拟体内皮下、真皮和表皮的微环境。将 PCS-201（真皮成纤维细胞）和 HaCaT（角质形成细胞）共培养在支架上，通过细胞增殖、分化和组织排列，成功实现了皮肤的再生。与标准治疗相比，支架在体内也显示出更好的伤口愈合效果，表现在更快的伤口闭合和适当的组织再生。总之，本研究成功建立了一种简单的、一步法合成功能梯度、可生物降解的支架，用于全层皮肤创面的无瘢痕、原生样、结构和功能再生。由于成本效益高、合成工艺简单和微观结构特征，设计的支架具有转化为良好商业伤口愈合产品的潜力。
