Multifunctional Layered HPMC/PCL-59S Bioactive Glass Patches for Improved <i>In Vivo</i> Wound Healing with Potent Anti-Inflammatory and Angiogenic Effects

Effective wound healing requires multifunctional biomaterials that support rapid tissue regeneration while providing structural integrity, biocompatibility, and therapeutic functionality. The successful fabrication of stacked patches was achieved through spin coating and electrospinning techniques, ensuring precise layering and seamless integration of Hydroxypropyl Methylcellulose (HPMC), Polycaprolactone (PCL), and 59S Bioglass (BG). The homogeneous dissolution of HPMC and PCL in the trisolvent mixture played a crucial role in achieving a uniform solution, facilitating the formation of well-structured layers. This integration enhanced the composite's structural and functional properties, with FESEM revealing a fibrous morphology and distinct layer differentiation. Degradation studies showed consistent weight loss in CP, CPD, and stacked patches over time particularly during the first 3 days, highlighting their stability. The stacked mat exhibited desirable mechanical properties with distinct elastic, strain-hardening, and fracture regions, achieving a tensile strength of 6.14 MPa and sufficient flexibility. Rapid degradation of the CB patches within 1 day emphasized the necessity of layer integration. The stacked patches exhibited superior biocompatibility with a reduced hemolysis rate (0.282%) and sustained metformin release over 3 days, crucial for inflammation management and tissue regeneration. The combination of HPMC/bioglass and HPMC/PCL/metformin demonstrated significant anti-inflammatory effects, inhibiting COX, LOX, MPO, and iNOS activities while reducing nitrite levels. Additionally, assays indicated a proliferation rate exceeding 90%, enhanced cell viability, angiogenesis, and antibacterial activity underscoring the stacked patches potential for wound healing. The combined attributes of structural stability, biocompatibility, efficient drug release, and anti-inflammatory efficacy represent a notable advancement in wound care with the potential to expedite the healing process. The <i>in vivo</i> studies demonstrated that the stacked patches significantly expedited wound closure, leading to full healing within 14 days. Histological evaluation evidently revealed enhanced tissue regeneration, characterized by rapid re-epithelialization, enhanced collagen formation, as well as increased vascularization, while also displaying a notable reduction in inflammation. Moreover, the lack of histopathological abnormalities in the examined organs obviously confirms their biocompatibility, reinforcing their suitability as a promising multifunctional biomaterial for advanced wound healing applications.