Abstract：
Hypertrophic scar (HS) is an unfavorable skin disorder that typically develops after trauma, burn injury, or surgical procedures and causes numerous physical and psychological issues in patients. Currently, intralesional multi-injection of corticosteroid, particularly compound betamethasone (CB), is one of the most prevalent treatments for HS. However, injection administration could result in severe pain and dose-related side effects. Additionally, the vacuum therapeutic efficacy of this treatment relies on the level of expertise of the healthcare professional. To overcome the limitations of conventional injections, a new method that is convenient, painless, and self-administrable is urgently required. In this study, we developed a methacrylate gelatin (GelMA)/polyethylene glycol diacrylate (PEGDA) double-network hydrogel microneedle patch loaded with CB (CB-HMNP) as an intradermal delivery system for HS treatment. The double-network structure conferred the CB-HMNP with sufficient mechanical properties to successfully penetrate scar tissue while also helping to regulate the drug\'s sustained release rate. Subsequently, we confirmed that the CB-HMNP had a pronounced inhibitory effect on human HS fibroblasts (hHSFs), whereas drug-free HMNPs had no effect on hHSFs, indicating its high biocompatibility. In order to assess the therapeutic efficacy of CB-HMNPs, HS models of New Zealand rabbit ears were developed. The administration of CB-HMNP three times significantly decreased the scar elevation index (SEI), collagen I/III, and transforming growth factor-β1 (TGF-β1) protein. Therefore, the CB-HMNP may offer an administration pathway for the treatment of HS that is less painful, more convenient, less invasive, and sustain-released.
摘要：
肥厚性瘢痕（HS）是一种不利的皮肤疾病，通常在创伤后发展，烧伤,或外科手术，并导致患者的许多生理和心理问题。目前,病灶内多次注射皮质类固醇，特别是复方倍他米松（CB），是HS最普遍的治疗方法之一。然而,注射给药可能导致严重的疼痛和剂量相关的副作用。此外,这种治疗的真空治疗效果取决于医疗保健专业人员的专业知识水平。为了克服常规注射的局限性，一种方便的新方法，无痛,迫切需要自我管理。在这项研究中,我们开发了一种负载有CB(CB-HMNP)的甲基丙烯酸酯明胶(GelMA)/聚乙二醇二丙烯酸酯(PEGDA)双网络水凝胶微针贴片作为HS治疗的皮内递送系统。双网络结构赋予CB-HMNP足够的机械性能以成功穿透瘢痕组织，同时也有助于调节药物的持续释放速率。随后，我们证实，CB-HMNP对人HS成纤维细胞（hHSF）有明显的抑制作用，而无药HMNPs对hHSF没有影响，表明其高生物相容性。为了评估CB-HMNPs的治疗效果，建立了新西兰兔耳的HS模型。3次给予CB-HMNP可显著降低瘢痕升高指数(SEI),胶原蛋白I/III，和转化生长因子-β1（TGF-β1）蛋白。因此,CB-HMNP可能为HS的治疗提供一种疼痛较小的给药途径，更方便,侵入性较小，持续释放。
