Design of a biofluid-absorbing bioactive sandwich-structured Zn-Si bioceramic composite wound dressing for hair follicle regeneration and skin burn wound healing

Abstract

The deep burn skin injures usually severely damage the dermis with the loss of hair follicle loss, which are difficult to regenerate. Furthermore, severe burns often accompanied with large amount of wound exudates making the wound moist, easily infected, and difficult to heal. Therefore, it is of great clinical significance to develop wound dressings to remove wound exudates and promote hair follicle regeneration. In this study, a sandwich-structured wound dressing (SWD) with Janus membrane property was fabricated by hot compression molding using hydrophilic zinc silicate bioceramics (Hardystonite, ZnCS) and hydrophobic polylactic acid (PLA). This unique organic/inorganic Janus membrane structure revealed excellent exudate absorption property and effectively created a dry wound environment. Meanwhile, the incorporation of ZnCS bioceramic particles endowed the dressing with the bioactivity to promote hair follicle regeneration and wound healing through the release of Zn²⁺ and SiO₃ ^2- ions, and this bioactivity of the wound dressing is mainly attributed to the synergistic effect of Zn²⁺ and SiO₃ ^2- to promote the recruitment, viability, and differentiation of hair follicle cells. Our study demonstrates that the utilization of the Janus membrane and synergistic effect of different type bioactive ions are effective approaches for the design of wound dressings for burn wound healing.

Keywords: Burn wound healing; Hair follicle regeneration; Janus membrane); Sandwich-structured wound dressing; Zn2+ and SiO32−.

Graphical abstract

Fig. 1

A biofluid absorbing sandwich-structured wound dressing (SWD) designed by organic-inorganic hybrid Janus membrane containing hardystonite (ZnCS, Ca₂ZnSi₂O₇) and the application in deep burn wound healing with enhanced hair growth and angiogenesis. (The wound fluid is absorbed by the powder in the sandwich dressing, which then releases bioactive ions for stimulating the regeneration of blood vessels and hair follicles.) (a) The design and preparation of the ZnCS-SWD. (b) ZnCS-SWD promote burn wound healing and hair follicle regeneration.

Fig. 2

Material characterization of ZnCS sandwich-structured wound dressing (ZnCS-SWD) (PLA fiber membrane was used for comparison). (a) The macroscopic appearance of the ZnCS-SWD. (b) The SEM of the ZnCS-SWD (Outside: the side not in contact with the ceramic powders; Inside: the side directly in contact with the ceramic powders). (c) Photos of the water contact angle of the ZnCS-SWD surface. (d) Quantitation of the contact angle of the ZnCS-SWD. (e) The water absorption performance of the ZnCS-SWD (1*1 cm²) with different amount of bioceramic powders. (f) The ion release of the ZnCS-SWD (1*1 cm²) by soaking in PBS at 37 °C for 24 h.

Fig. 3

(a) Establishment of a burn animal model using a hot metal iron bar and use sandwich-structured wound dressing for treatment. (b) Wound closure after treatment with sandwich-structured wound dressing. Wound area images on the 0^th, 3rd, 10th, 17th, and 24th day after treatment with different materials (blank was treated with PLA dressings). (c) Quantitation of wound closure rate of composite membranes (n = 4). (d) Images of H&E staining of wound sections on the 10th and 24th day (BW: Burn wound; NE, newly formed epidermis; ND, newly formed dermis; HF, newly formed hair follicle). *P < 0.05 and **P < 0.01.

Fig. 4

(a) Images of immunohistochemical staining for cytokeratin 19 on the 10th and 24th day (HF, newly formed hair follicles). (b) Number of hair follicles on the 24th day (n = 6). (c) Images of immunohistochemical staining for CD31 on the 10th and 24th day (BV, blood vessels). (d) Number of blood vessels on the 10th and 24th day. (e) Vessel diameter distribution on the 24th day. (*P < 0.05, **P < 0.01, n = 3).

Fig. 5

Synergistic effect of Zn and Si ions on the migration, viability and gene expression of hair follicle dermal papilla cells (HHDPCs) (1/16 ZnCS extracts were used as Zn and Si ions solution. CS extracts (CS) and Zinc chloride solution (Zn) with same concentration were used as control groups). (a) The synergistic effect of Zn and Si ions on the migration of HHDPCs cells (Ruler Length = 200 μm). (b) Migration rate of HHDPCs. (c) The synergistic effect of Zn and Si ions on the viability of HHDPCs. (d) The synergistic effect of Zn and Si ions on genes (VEGF, BMP-6, KGF, HGF, PDGF-α, PDGF-β, and C-Myc) related to the hair follicle growth in HHDPCs (*P < 0.05, **P < 0.01, ***P < 0.001).