Abstract

Dermal lesions and chronic wounds associated with burns or some diseases like diabetes are the more important public health concerns which can affect the quality of life. Currently, tissue engineering is considered as the most effective therapeutic method although the design of polymeric substrates for epidermal-dermal differentiation and wound healing (scar-free) is the main challenge. For this purpose, we designed a hybrid three-dimensional scaffold (CPCP) based on collagen/chitosan modified by PEG/PCL composite that can imitate differentiation pattern of both epidermis/dermis cells, via mimicking the structure and function of human skin. The physicochemical, mechanical and biological properties of designed scaffolds were evaluated to study their function for skin tissue engineering applications. Comparison of FTIR analysis showed a chemical similarity between CPCP and decellularized dermal matrix (DDM). Our results showed that combination of two natural/two synthetic polymers led to the formation of stronger 3D-network together with higher modulus (-18), water absorption (4-fold), porosity (-92) and consequently lower pores size (-54 um), compared to natural, synthetic and natural/ synthetic copolymer-based scaffolds. The observation of human skin fibroblast cells proliferation and morphology showed that CPCP was more beneficial to cell adhesion, proliferation, and extension than that of other designed scaffolds due to its hydrophilicity and higher wettability (WCA=60°). According to the results of RT-PCR, the more expression of epidermal-dermal keratinocytes induced by human-adipose-derived stem cells was observed on the CPCP along with a pattern similar to skin. The results demonstrate CPCP can act as a super-absorbent substrate/dressing for continuous absorption of wound exudates. Furthermore, it can potentially be effective for re-epithelialization of skin together with its derivative (hair follicles, sebaceous/sweat glands). This study indicates new insights into the design of skin- engineered scaffolds.

中文翻译：

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新型3D脚手架的设计作为潜在材料来诱导人脂肪干细胞的表皮-真皮角质形成细胞并促进成纤维细胞增殖以促进皮肤再生

摘要

与烧伤或某些疾病（如糖尿病）相关的皮肤病变和慢性伤口是更重要的公共卫生问题，可能会影响生活质量。目前，组织工程学被认为是最有效的治疗方法，尽管设计用于表皮-皮肤分化和伤口愈合（无疤痕）的聚合物基质是主要挑战。为此，我们设计了一种基于胶原蛋白/壳聚糖的复合三维支架（CPCP），该支架由PEG / PCL复合材料修饰，可通过模仿人类皮肤的结构和功能来模仿表皮/真皮细胞的分化模式。评价了设计支架的物理化学，机械和生物学特性，以研究其在皮肤组织工程应用中的功能。FTIR分析的比较显示CPCP和脱细胞真皮基质（DDM）之间的化学相似性。我们的结果表明，两种天然/两种合成聚合物的结合可导致形成更坚固的3D网络，并具有较高的模量（-18），吸水率（4倍），孔隙率（-92）以及因此较小的孔尺寸（-与天然，合成以及基于天然/合成共聚物的脚手架相比）。对人皮肤成纤维细胞增殖和形态的观察表明，由于CPCP具有亲水性和较高的可湿性（WCA = 60°），因此它比其他设计的支架更有利于细胞粘附，增殖和扩展。根据RT-PCR的结果，在CPCP上观察到了由人脂肪干细胞诱导的表皮-真皮角质形成细胞的更多表达以及与皮肤相似的模式。结果表明CPCP可以用作伤口渗出液的连续吸收的超吸收基质/敷料。此外，它和其衍生物（毛囊，皮脂腺/汗腺）一起可能对皮肤的重新上皮形成有效。这项研究表明了对皮肤工程支架设计的新见解。