Chronic wounds, including diabetic foot ulcers (DFUs), venous leg ulcers (VLUs), and pressure injuries, remain a major global health burden and contribute substantially to Medicare spending. Because traditional wound dressings fail to address the dynamic microenvironment of chronic wounds, bioactive materials that modulate inflammation and support tissue regeneration are needed. In this study, we evaluated the tissue response to our borate-based bioactive glass fiber matrix (BBGFM) designed to overcome limitations of existing fibrous wound dressings. Two Sus scrofa domesticus underwent creation of twelve 5 × 5 cm subcutaneous pockets each, which were treated with BBGFM at three thicknesses (25%, 50%, and 100%) or left untreated as controls. One animal was euthanized at three weeks and the other at six weeks for gross and histopathological evaluation of all wound sites. BBGFM-treated pockets demonstrated a dose-dependent increase in inflammation at three weeks that diminished by six weeks. Enhanced neovascularization and collagen matrix deposition were also seen at both time points. Collagen maturity increased across all groups by six weeks, and residual BBGFM correlated with initial implant thickness. These findings indicate that BBGFM promotes a controlled inflammatory response and supports neovascularization and matrix remodeling in a dose-dependent manner, suggesting its potential as an effective bioactive wound matrix.