# Comparative Effects of Cellulose- and Gelatin-Based Hemostatic Biomaterials on the Early Stage of Wound Healing—An In Vivo Study

## TL;DR

This study compares how cellulose- and gelatin-based hemostatic materials affect early wound healing in mice, finding that gelatin-based materials support better healing without causing excessive inflammation.

## Contribution

The study provides new in vivo evidence on how different hemostatic biomaterials influence early wound healing processes.

## Key findings

- Gelatin-based materials showed enhanced extracellular matrix deposition and increased macrophage presence.
- GELA group exhibited elevated Ki-67 expression, indicating enhanced cellular proliferation.
- None of the biomaterials impaired wound healing or caused excessive inflammation.

## Abstract

Hemostatic biomaterials are widely used in surgical and trauma settings, yet their influence on early wound healing remains incompletely understood. This in vivo study investigated the effects of cellulose- and gelatin-based hemostatic biomaterials on early wound healing using a murine skin wound model. Oxidized non-regenerated cellulose (ONRC), oxidized regenerated cellulose (ORC), and a porcine gelatin-based matrix (GELA) were left in situ following standardized subcutaneous implantation and compared with sham-treated controls. Tissue responses were analyzed at postoperative days 3 and 7 using histology, immunohistochemistry, and quantitative real-time polymerase chain reaction (qPCR). Cellulose-based materials persisted as eosinophilic remnants, whereas fibrous matrix structures and enhanced extracellular matrix deposition were observed in the GELA group. Immunohistochemical analysis revealed increased cluster of differentiation 68 (CD68)–positive macrophage presence in the ORC group at day 3 and in the GELA group at day 7, indicating biomaterial-dependent modulation of macrophage involvement during early wound healing. Expression of Kiel 67 (Ki-67), a marker of cellular proliferation, was significantly elevated in the epidermis of the GELA group at day 7, suggesting enhanced proliferative activity during the reparative phase. In contrast, no significant differences were detected in the expression of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), or cluster of differentiation 14 (CD14) between groups. Overall, none of the investigated biomaterials impaired early wound healing, while the gelatin-based material demonstrated features consistent with enhanced reparative cellular responses without excessive inflammation.