Advances and applications of biomimetic biomaterials for endogenous skin regeneration

Abstract

Endogenous regeneration is becoming an increasingly important strategy for wound healing as it facilitates skin's own regenerative potential for self-healing, thereby avoiding the risks of immune rejection and exogenous infection. However, currently applied biomaterials for inducing endogenous skin regeneration are simplistic in their structure and function, lacking the ability to accurately mimic the intricate tissue structure and regulate the disordered microenvironment. Novel biomimetic biomaterials with precise structure, chemical composition, and biophysical properties offer a promising avenue for achieving perfect endogenous skin regeneration. Here, we outline the recent advances in biomimetic materials induced endogenous skin regeneration from the aspects of structural and functional mimicry, physiological process regulation, and biophysical property design. Furthermore, novel techniques including in situ reprograming, flexible electronic skin, artificial intelligence, single-cell sequencing, and spatial transcriptomics, which have potential to contribute to the development of biomimetic biomaterials are highlighted. Finally, the prospects and challenges of further research and application of biomimetic biomaterials are discussed. This review provides reference to address the clinical problems of rapid and high-quality skin regeneration.

Graphical abstract

Fig. 1

Feature size of each biological structure in nature and its corresponding material on the same scale.

Fig. 2

The major tissue structures of the skin and their corresponding biomimetic biomaterials that promote structural and functional regeneration. Created with BioRender.com.

Fig. 3

Schematics of skin wound microenvironment by natural hemostasis (a, b); accelerated wound closure by tissue adhesives and two strategies to improve the adhesion of tissue adhesives (c).

Fig. 4

Schematics of polarization, classification and function of macrophages (a); Two main strategies of regulating macrophage polarization by biomaterials, and their main influence factors and loaded bioactive components (b). MCSF, macrophage colony-stimulating factor; LPS, lipopolysaccharide; MerTK, c-Mer proto-oncogene tyrosine kinase; TLR, toll-like receptors. Created with BioRender.com.

Fig. 5

Array of silk fibroin microneedle patch (a); Schematic diagram of rabbit ear scar models and the position SF MN patches treat rabbit ear scar (b); Photos of post-treated scar tissues. (c); Changes in thickness of scar tissues before and post-treatment (d); Dumbbell-shaped mechanical test specimens of uninjured skin and scars in the direction of the axial axis (e); Western blotting and semiquantitative statistics of protein levels of TGF-β1, α-SMA, and ANKRD1 (f); CLSM of the intracellular F-actin meshwork of fibroblasts under different treatments (g); Illustration of SF MN interrupting the mechanical communication between fibroblasts and the ECM (h). Reprinted from Ref. [83].

Fig. 6

Schematic diagram of current therapeutic strategies for hair follicle regeneration and their corresponding biomaterial in recent reports. The strategies of endogenous regeneration of hair follicle are marked with the dashed box.

Fig. 7

Schematic diagram of exosomes composited with biomaterial vehicles (a); Schematic of composition (i, ii) and skin insertion (iii) of microneedle patch as applied for hair regeneration (b); Photographs of mice treated with microneedle patch or minoxidil respectively. Reprinted from Refs. [122,124].

Fig. 8

(A) Surface topography of random, aligned, and latticed electrospun membranes. (B) Workflow for evaluating rat skin wound healing. PCR, polymerase chain reaction. (C) Surgical processes for the rat skin excisional wound model. (D and E) Residual wound area at 3, 5, 7, and 14 days. Reprinted from Ref. [182].

Fig. 9

Schema of the synergy of the ROS and photothermal effects in the germ-killing response of PB-PCN-224 (a); The crystal structure diagram of PB-PCN-224 (b); The spread plate images and antibacterial rate of PB-PCN-224 against S. aureus (c); SEM pictures of the morphology of S. aureus treated with or without 660 nm light irradiation (d); The protein leakage concentration of S. aureus treated or not treated with 660 nm light irradiation (e). Reprinted from Ref. [214].

Fig. 10

Schematic diagram of five promising novel techniques that have potential to be used in skin regeneration applications: in situ cell reprogramming, novel flexible electronic skin, artificial intelligence, single-cell sequencing, and spatial transcriptomics technology. Reprinted from Refs. [[250], [251], [252]], created with BioRender.com.