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用于伤口愈合中靶向递送表皮生长因子和木瓜蛋白酶的功能化丝素蛋白与粘蛋白杂化材料

Functionalized Silk Fibroin and Mucin Hybrid Material for Targeted EGF and Papain Delivery in Wound Healing.

作者信息

Barros Fernando José Soares, Lopes Laise Maia, Ilk Sedef, Vieira Rodrigo Silveira, Crouzier Thomas, de Moraes Mariana Agostini, Beppu Marisa Masumi

机构信息

KTH Royal Institute of Technology, Department of Chemistry, Division of Glycoscience, SE-10044 Stockholm, Stockholm County, Sweden.

State University of Campinas (UNICAMP), School of Chemical Engineering, Department of Materials and Bioprocess Engineering, Av Albert Einstein, 500, CEP 13083-852 Campinas, SP, Brazil.

出版信息

ACS Omega. 2025 Aug 13;10(33):37432-37444. doi: 10.1021/acsomega.5c03320. eCollection 2025 Aug 26.

Abstract

Silk fibroin (SF) and mucin are extensively recognized as promising biomaterials for wound dressings due to their outstanding biocompatibility, biodegradability, and ability to support cell growth and tissue regeneration. In this study, we developed a hybrid SF/mucin wound dressing (HYB) using tetrazine and norbornene click chemistry to enhance its structural and functional properties. The robust assembly resulted in a dual-phase material with a dense SF membrane and a porous mucin hydrogel (MH). Scanning electron microscopy confirmed the successful integration and tight adhesion between these polymers. The hybrid material exhibited a controlled release of bioactive agents, with epidermal growth factor (EGF) showing a sustained release of up to 48% over 48 h. The optimized 25 mg/mL mucin hydrogel showed efficient EGF release and performance comparable to higher concentrations. It was selected for papain loading to reduce material usage without compromising efficacy. HYB showed a higher papain release rate of 36% compared to the bare SF membrane. Additionally, the hybrid material exhibited enhanced mechanical strength, optimized water vapor permeability comparable to commercial wound dressings, and improved cell proliferation relative to its individual components. Cytotoxicity assays demonstrated that the papain-loaded hybrid material is a viable candidate for wound dressing applications. These results suggest that the click-chemistry-functionalized SF/mucin hybrid material holds significant potential as an advanced wound dressing, capable of promoting tissue regeneration while maintaining a moist environment conducive to healing.

摘要

丝素蛋白(SF)和粘蛋白因其出色的生物相容性、生物降解性以及支持细胞生长和组织再生的能力,被广泛认为是用于伤口敷料的有前景的生物材料。在本研究中,我们利用四嗪和降冰片烯点击化学开发了一种混合SF/粘蛋白伤口敷料(HYB),以增强其结构和功能特性。这种强大的组装形成了一种双相材料,其中有致密的SF膜和多孔的粘蛋白水凝胶(MH)。扫描电子显微镜证实了这些聚合物之间的成功整合和紧密粘附。该混合材料表现出生物活性剂的可控释放,表皮生长因子(EGF)在48小时内持续释放高达48%。优化后的25mg/mL粘蛋白水凝胶显示出高效的EGF释放,其性能与更高浓度的相当。它被选择用于负载木瓜蛋白酶,以减少材料用量而不影响疗效。与裸露的SF膜相比,HYB显示出更高的木瓜蛋白酶释放率,为36%。此外,该混合材料表现出增强的机械强度,与商业伤口敷料相当的优化水蒸气透过率,以及相对于其单个组分而言改善的细胞增殖。细胞毒性试验表明,负载木瓜蛋白酶的混合材料是伤口敷料应用的可行候选物。这些结果表明,点击化学功能化的SF/粘蛋白混合材料作为一种先进的伤口敷料具有巨大潜力,能够促进组织再生,同时保持有利于愈合的湿润环境。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0495/12391997/ba64d372495d/ao5c03320_0001.jpg

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