长效可控药物释放静电纺纤维支架构建及抗增生性瘢痕研究

Hypertrophic scars (HS) are medical complications of skin repair after three months. At present, most of therapeutic methods inhibit hypertrophic scars after its formation. They are not able to prevent scar hyperplasia in the long term while repairing tissue damage. Electrospun fibrous scaffolds have the advantages of a high surface area to mimic native extracellular matrix and a potential to be used as a drug delivery system. Previously, we fabricated near superhydrophobic electrospun fibrous scaffolds through combining drug-loaded mesoporous silica and electrospun fibers, and the drug release time researched more than 100 days. However, we further found that the hydrophobic electrospun scaffolds are not suitable for cell adhesion and growth. In this study, molecular brush modified mesoporous silica nanoparticles (MB-MS) were prepared through free radical initiated polymerization, and electrospun composite fibers were fabricated through containing drug-loaded MB-MSs which did not change surface wettability of the electrospun scaffolds. The drug release rate could be controlled through adjusting length and density of molecular brush, and drugs continually release after more than 100 days. While investigating the long-term drug release mechanism of electrospun composite fibers, the study will focus on the effect of the molecular brush density and length on drug releasing. The goal of this project is to reveal the relations between biocompatibility and initial drug release of scaffolds. Moreover, it will establish the mechanism of promoting repairing tissue damage in the early stage and of inhibiting scar hyperplasia in the late stage. This research, from the perspective of combining treatment, provides a scientific basis for functional applications of long-term drug carriers of cell growth scaffolds.

增生性瘢痕是损伤皮肤修复3月后的并发症，目前治疗方案仅在瘢痕形成后对其进行干预，无法在创伤修复的同时实现长期预防瘢痕形成。静电纺纤维是一种集细胞生长支架和药物载体为一体的多功能修复支架。前期，我们通过静电纺纤维复合载药介孔二氧化硅，构建近超疏水型纤维支架，实现了药物100天以上的长效释放，但疏水支架不利于细胞粘附和生长。本研究通过"活性"可控自由基聚合法在介孔二氧化硅表面接枝分子刷，装载药物后复合到静电纺纤维内，在不改变纤维膜润湿性前提下，通过介孔表面分子刷密度和长度调控纤维内药物释放速率，实现药物100天以上的长效释放，并确定其对药物释放速率的调控规律。探讨静电纺复合纤维内中药物长效释放机理。明确复合纤维细胞相容性和初期药物释放量的关系。阐明复合纤维初期促进损伤组织修复和后期抑制增生性瘢痕产生的机制。本研究将从一体化治疗这个新视点为细胞生长支架的长效药物释放体系提供新思路。

增生性瘢痕是整形外科最常见疾病之一，其中物理和化学治疗是其中主要突破口。抗肿瘤药物和激素类药物联合注射治疗为主要治疗方法，该方法存在药物周期短及毒副作用等问题。本研究分别从长效药物制剂角度出发，系统研究其抑制瘢痕增生的效果和相关机制。采用静电纺丝技术研制携载药物的微纳米纤维膜缓释制剂并对其进行透明质酸包被，改善载药纤维膜的生物相容性，用于兔耳瘢痕创面，观察其对瘢痕形成的影响。通过聚合物颗粒预载药结合静电纺载药纤维技术构建出携载药物的聚合物颗粒纳米纤维长效缓释制剂，进一步行动物实验，观察其抗瘢痕治疗的作用。长效释放药物的纤维膜可早期促进创面愈合和皮肤修复，并在晚期抑制瘢痕增生，结合皮肤组织修复再生和抑制瘢痕增生联合综合治疗瘢痕，可达更佳的抑制瘢痕增生效果；携载药物的聚合物颗粒纳米纤维制剂可实现药物更长时间的释放（可长效释放达到120 d以上），在早期促进皮肤创面修复同时，在后期及更长时间（>120 d）发挥抑制瘢痕增生作用。从物理和化学治疗角度出发，提出药物和生物力学治疗方案，研究其作用机制。长效释放药物的纤维膜可实现早期促修复，后期抗瘢痕作用，进一步研制携载药物的聚合物颗粒纳米纤维制剂，可实现药物长达120天的释放和抗瘢痕增生作用。明确复合纤维细胞相容性和初期药物释放量的关系。阐明复合纤维初期促进损伤组织修复和后期抑制增生性瘢痕产生的机制。本研究将从一体化治疗这个新视点为细胞生长支架的长效药物释放体系提供新思路。