α-Bisabolol-Loaded Cross-Linked Zein Nanofibrous 3D-Scaffolds For Accelerating Wound Healing And Tissue Regeneration In Rats

Abstract

Sarah A El-Lakany,1 Ahmed I Abd-Elhamid,2 Elbadawy A Kamoun,3,4 Esmail M El-Fakharany,5 Wael M Samy,1 Nazik A Elgindy1 1Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 2Nanotechnology and Composite Material Research Department, Advanced Technology and New Materials Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Alexandria 21934, Egypt; 3Polymeric Materials Research Department, Advanced Technology and New Materials Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Alexandria 21934, Egypt; 4Nanotechnology Research Center (NTRC), The British University in Egypt (BUE), El-Sherouk City, Cairo 11837, Egypt; 5Therapeutic and Protective Proteins Laboratory, Protein Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Alexandria 21934, EgyptCorrespondence: Sarah A El-LakanyDepartment of Industrial Pharmacy Faculty of Pharmacy, Alexandria University, 1 El Khartoum Square, PO Box 21521, Alexandria, EgyptTel [phone]Fax [phone]Email [email protected]: Novel α-bisabolol (BIS)-loaded citric acid cross-linked zein nanofibrous scaffolds (C-ZNFs) were proposed to serve as safe platforms for promoting wound repair in rats.Methods: ZNFs were synthesized using electrospinning technique, then NFs, with adequate water resistance, were produced using citric acid as a safe cross-linker.Results: Compared to the uncross-linked ZNFs, cross-linking with 7% w/w citric acid decreased swelling index by 3 folds, while the tensile strength and the contact angle were enhanced to 2.5 and 3.8 folds, respectively. SEM images showed beads-free homogeneous NFs with a fully inter-connected 3D-network, where the average diameter of optimized C-ZNFs was 181.7±50 nm. After 24 h, C-ZNFs exhibited a decreased BIS release rate (45.6%), compared to uncross-linked mats (84.9%). By increasing BIS concentration, the cell adhesion (WI38 fibroblasts) was improved which can be attributed mainly to BIS activation of transforming growth factor-beta (TGF-β1). The MTT-OD obtained values indicated that all tested zein scaffolds significantly enhanced the viability of WI38 fibroblasts, compared to the control after 48h of incubation which can be referred to the proliferative potential of zein by provoking cell spreading process. The scratch wound assay demonstrated that BIS-loaded ZNF scaffolds showed accelerated migration and proliferation of fibroblasts expressed by significantly higher wound closure rates compared to the control sample. BIS-loaded-C-ZNFs prominently accelerated tissue regeneration for wound closure demonstrated by entirely grown epithelium with normal keratinization and rapid wound contraction, compared to the control. Immunohistochemical results confirmed the superiority of BIS-loaded-C-ZNFs, where the observed reduced NF-κB and the elevated cytokeratin expressions confirmed the anti-inflammatory and proliferative effects of the scaffolds, respectively.Conclusion: In-vitro, optimized C-ZNFs offered a satisfactory cytocompatibility, adhesion and healing which were consistent with the in-vivo results. BIS-loaded-C-ZNFs could be regarded as a promising and effective biomaterial for tissue regeneration and for accelerating the wound healing process.Keywords: cell compatibility, electrospinning, German chamomile, fiber mats

Keywords

• Cell compatibility
• electrospinning
• German chamomile
• fiber mats.