N-acetyl cysteine-loaded graphene oxide-collagen hybrid membrane for scarless wound healing
N-acetyl cysteine-loaded graphene oxide-collagen hybrid membrane for scarless wound healing
复制标题
N-乙酰半胱氨酸负载氧化石墨烯-胶原蛋白杂化膜用于无疤痕伤口愈合
DOI：
10.7150/thno.34480
复制
发表时间：
2019-01-01
期刊：
影响因子：
12.4
通讯作者：
Wang, Zhenxing
中科院分区：
文献类型：
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作者：
Li, Jialun;Zhou, Chuchao;Wang, Zhenxing
由I型胶原等天然聚合物组成的伤口敷料具有良好的生物相容性、保水性、透气性和可降解性，可用于伤口修复。然而，由于伤口区域持续存在氧化应激，成纤维细胞的迁移和增殖可能受到抑制，导致愈合不良。因此，含胶原蛋白支架不适合加速伤口愈合。抗氧化剂N-乙酰半胱氨酸（NAC）已知可减少活性氧（ROS），并已广泛应用于临床。理论上，NAC的羧基可以负载氧化石墨烯（GO）并持续释放，还可以增强胶原支架的机械性能，使其成为更好的伤口敷料材料。在此，我们展示了一种潜在的皮肤再生混合膜的创新方法，该方法使用与胶原蛋白 I 和 NAC (N-Col-GO) 结合的 GO，能够持续释放抗氧化剂 NAC。方法：体外测量N-Col-GO杂化膜的机械稳定性、持水能力和生物相容性。创建20毫米大鼠全皮缺损模型来评估N-Col-GO杂化膜的修复效率。还检查了伤口区域的血管化和疤痕相关基因。结果：与仅Col支架相比，N-Col-GO杂化膜表现出更好的机械性能、更强的保水能力和更慢的NAC释放能力，这可能促进成纤维细胞迁移和增殖。在大鼠伤口模型中使用 N-Col-GO 杂化膜进行治疗后，显示出应用后 14 天完全愈合，比对照组快了 22%。 HE 和 Masson 染色证实了更快的胶原沉积和更好的上皮化，而 CD31 染色显示血管化明显增加。此外，Rt-PCR 证明促纤维化的 mRNA 表达降低，抗纤维化因子过度表达，表明抗疤痕效果。结论：这些研究结果表明，N-Col-GO 药物释放杂化膜可以作为无疤痕皮肤再生的更好平台。
Wound dressings composed of natural polymers, such as type I collagen, possess good biocompatibility, water holding capacity, air permeability, and degradability, and can be used in wound repair. However, due to the persistent oxidative stress in the wound area, the migration and proliferation of fibroblasts might be suppressed, leading to poor healing. Thus, collagen-containing scaffolds are not suitable for accelerated wound healing. Antioxidant N-acetyl cysteine (NAC) is known to reduce the reactive oxygen species (ROS) and has been widely used in the clinic. Theoretically, the carboxyl group of NAC allows loading of graphene oxide (GO) for sustained release and may also enhance the mechanical properties of the collagen scaffold, making it a better wound-dressing material. Herein, we demonstrated an innovative approach for a potential skin-regenerating hybrid membrane using GO incorporated with collagen I and NAC (N-Col-GO) capable of continuously releasing antioxidant NAC. Methods: The mechanical stability, water holding capacity, and biocompatibility of the N-Col-GO hybrid membrane were measured in vitro. A 20 mm rat full-skin defect model was created to evaluate the repair efficiency of the N-Col-GO hybrid membrane. The vascularization and scar-related genes in the wound area were also examined. Results: Compared to the Col only scaffold, N-Col-GO hybrid membrane exhibited a better mechanical property, stronger water retention capacity, and slower NAC release ability, which likely promote fibroblast migration and proliferation. Treatment with the N-Col-GO hybrid membrane in the rat wound model showed complete healing 14 days after application which was 22% faster than the control group. HE and Masson staining confirmed faster collagen deposition and better epithelization, while CD31 staining revealed a noticeable increase of vascularization. Furthermore, Rt-PCR demonstrated decreased mRNA expression of profibrotic and overexpression of anti-fibrotic factors indicative of the anti-scar effect. Conclusion: These findings suggest that N-Col-GO drug release hybrid membrane serves as a better platform for scarless skin regeneration.