The Potential of Composite Cements for Wound Healing in Rats

Abstract

Recent developments in biomaterials have resulted in the creation of cement composites with potential wound treatment properties, even though they are currently mainly employed for bone regeneration. Their ability to improve skin restoration after surgery is worth noting. The main purpose of this research is to evaluate the ability of composite cement to promote wound healing in a rat experimental model. Full-thickness 5 mm skin defects were created, and the biomaterials were applied as wound dressings. The hybrid light-cured cement composites possess an organic matrix (Bis-GMA, TEGDMA, UDMA, and HEMA) and an inorganic phase (bioglasses, silica, and hydroxyapatite). The organic phase also contains γ-methacryloxypropyl-trimethoxysilane, which is produced by distributing bioactive silanized inorganic filler particles. The repair of the defect is assessed using a selection of macroscopic and microscopic protocols, including wound closure rate, histopathological analysis, cytotoxicity, and biocompatibility. Both composites exerted a favorable influence on cells, although the C1 product demonstrated a more extensive healing mechanism. Histological examination of the kidney and liver tissues revealed no evidence of toxicity. There were no notable negative outcomes in the treated groups, demonstrating the biocompatibility and efficacy of these bioproducts. By day 15, the skin of both groups had healed completely. This research introduces a pioneering strategy by utilizing composite cements, traditionally used in dentistry, in the context of skin wound healing.

Keywords: biocompatibility; biomaterial; composite cement; skin wound healing; tissue engineering.

Figure 1

Representative images of bacterial colonies (A), processed on blood agar (B).

Figure 2

Representative images of full-thickness skin defects in Blank, C1, and C2 rats at 1, 3, 6, 11, and 15 days post-surgery (scale bar: 6 mm).

Figure 3

The evolution of wound healing is presented in 3D at 1, 3, 6, 11, and 15 days post-surgery (scale bar 6 mm).

Figure 4

Percentage of wound closure of the defect treated with C1 and C2 composite cements. Statistical evaluations performed using one- and two-way ANOVA; * p < 0.05; ** p < 0.01; *** p < 0.001.

Figure 5

Angiogenesis (%) on day 7 versus day 15.; pronounced vascularization in C1 groups; * p < 0.05.

Figure 6

Photomicrographs of skin and subcutis obtained on day 15 from the control group (A,C) and from rats treated with the C1 biomaterial (B,D). In the control group, the defect is filled with fibrous tissue composed of fibroblasts oriented parallel to the epidermis, collagen fibers, and blood vessels, and covered by a completely regenerated epidermis (A), H&E, 50 µm; multifocally, predominantly in the deep dermis, scattered lymphocytes and plasma cells are present within the scar tissue (C), H&E, 100 µm; (B): the defect is replaced by fibrous tissue composed of fibroblasts oriented parallel to the epidermis, mature collagen fibers, scattered inflammatory cells, mainly lymphocytes and plasma cells, and regenerated sebaceous units covered by a completely regenerated epidermis (B), H&E, 50 µm; (D): fragmented biomaterial present within the cytoplasm of the macrophages (black arrow) and rare multinucleated macrophages (white arrow) within the deep dermis, (D): H&E, 50 µm.

Figure 7

Photomicrographs of the dermis obtained for the area of the defect at 15 days post-surgery in C1 control case (A), C2 control case (C), rats treated with C1 biomaterial (B), and rats treated with C2 biomaterial. Biomaterial fragments (black arrow) (D); MT, 20 µm.

Figure 8

Normal skin thickness (%) compared with scar thickness (%) on day 15.

Figure 9

Photomicrographs of the skin and subcutis obtained on day 15 from the control group (A,C) and from rats treated with C2 biomaterial (B,D). The defect is replaced by mesenchymal cells oriented parallel to the regenerated epidermis, blood channels, and collagen fibers (A); H&E, 50 µm; within the deep dermis, a mild inflammatory infiltrate, mostly lymphocytes, plasma cells, and rare siderophages (white arrow) are present (D), H&E, 50 µm. (B): in the group treated with C2 biomaterial, the defect is filled by fibrous connective tissue, composed of spindle cells, blood vessels, collagen fibers, and scattered inflammatory cells (B); the pyogranulomatous reaction can be noted multifocally within the dermis, represented by macrophages, multinucleated macrophages (white arrows), and neutrophils centered on biomaterial fragments (black arrow), H&E, 50 µm.

Figure 10

Photomicrographs of the kidney and liver obtained on day 15 from the C1 group (A,B) and C2 group (C,D), with no significant findings noted; H&E, 100 µm.