1. Introduction
Assisting wounds healing with high efficacy is a research hotspot in the regenerative medicine. (Ying et al., 2019) In recent years, various types of wound-dressing materials containing growth factors to biomimetic extracellular matrix (ECM) have been more widely adopted to accelerate wound perfectly healing.(Choi et al., 2018; Thönes et al., 2019) Although extensive studies have been carried out around skin repair, but developing newer biodegradable dressings to promote wound healing are still enormous market demand.(Zoe, Elizabeth, June, & Louise, 2019) In particular, epidermal growth factor (EGF) plays key roles in skin wound repair.(J. et al.) Besides, as the most abundant ECM structural protein, collagen has good biocompatibility and degradability, and are considered as a better constituent for wound dressing preparations.(Davison-Kotler, Marshall, & Garcia-Gareta, 2019) We constructed a freeze-dried dressing based on recombinant human-like collagen (RHC) and EGF to confer a multifunctional product which can improve cell-biomaterial interactions and promote wound healing.
EGF is a typical growth factor that has been studied more in wound repair, which can bind to cell membrane receptors and exert various biological effects.(Duy et al.; Jones & Rappoport) In terms of the mechanism for promoting wound healing, one is that EGF are very powerful and can significantly promote keratinocytes and so on, and thus migrate to the injured site;(Jones & Rappoport; Schreier, Gekle, & Grossmann) the other is that as a mitogenic promoter, EGF promotes epithelial cell proliferation and division, improves collagen construction and regulates protein synthesis, thereby accelerating wound healing.(Berlanga-Acosta; Bodnar & J.; Lian & Li) In brief, EGF plays an essential role in wound healing .
Among recently available dressings, collagen-based dressings have shown to actively influence the healing process by intervening with various tissue components(Giriprasath et al.). Type I collagen can form fibrils through heterogeneous self-assembly compared with type II and type III collagen. (Irawan, Sung, Higuchi, & Ikoma, 2018; Jiang et al., 2016; Tiku & Madhan, 2016) Therefore, it is widely used as a biological material other than type II and type III collagen.(Sharma et al., 2017) However, the application of natural type I collagen is limited for its insolubility in water and poor processability. With the development of gene engineering, a series of highly hydrophilic, safe and effective recombinant human-like collagen (RHC) had attracted extensive attention worldwide. Many reports have been reported to expressed recombinant truncated type I human-like collagen peptides inE.coli ,(Guo et al., 2010; Yang et al.) whereas some of studies expressed recombinant type I human-like collagen peptides containing multiple identical motifs by means of codon optimization.(Olsen et al., 2005; Yao, Yanagisawa, & Asakura, 2004) Because these motifs are ligands for some types of integrin receptors, recombinant type I human-like collagen peptides is not only expected to enhance cell activity through certain integrin receptor binding, but also is extensible in various fibrous structural materials, including dressing.(Grab, Miles, Furcht, & Fields, 1996; Mashiko et al., 2018)
In this study, RHC consisting of cell adhesion domains derived from native type I collagen were designed and constructed by a genetic engineering method to construct a new type of RHC to overcome the deficiency of natural animal collagen. In addition, we prepared RHC/EGF freeze-dried dressing, and its potential applications for wound healing and repair were investigated using anin vivo full-thickness skin defects. Our results demonstrate that RHC/EGF freeze-dried dressing are a potentially useful tool for wound healing applications.