Integrating traditional herbal extracts into modern biomaterials offers a promising route for advanced wound care. A standardized Buddleja globosa Hope extract (BG-126), recognized for its therapeutic value, was incorporated into polymeric scaffolds with variable composition to explore their potential in promoting wound healing and controlling infections. This work aimed to identify the polymeric composition of a scaffold with BG-126 that maximizes its compatibility and antimicrobial properties. Scaffolds were developed by lyophilization using a Box–Behnken design (BBD) with chitosan, hyaluronic acid, and gelatin content as study factors. Thirteen scaffold formulations were tested for their antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa, including biofilm forms, as well as for their biocompatibility with normal human fibroblasts. Structural and physical properties, such as the moisture content and swelling capacity, were evaluated. The best-performing scaffold was analyzed using Raman spectroscopy. The chitosan content was strongly associated with antimicrobial efficacy, while gelatin enhanced fibroblast compatibility (R² ≥ 0.9). No correlations were identified between the polymeric content and biofilm inhibition or physical properties. BG-126-loaded scaffolds reduced planktonic and biofilm proliferation and improved fibroblast compatibility compared to the control scaffold (without BG-126). The results support the rational design of botanical-loaded scaffolds with targeted properties for wound healing.

Chronic wounds are frequently complicated by biofilm-associated infections that impair healing and limit treatment efficacy. Buddleja globosa (BG) exhibits antimicrobial and regenerative properties, making it a promising candidate for advanced wound care. This study aimed to optimize the concentration of a standardized BG extract incorporated into polymeric scaffolds for the treatment of wounds infected with the dual-species biofilm (DSB) of Pseudomonas aeruginosa and Staphylococcus aureus. Scaffolds containing increasing BG concentrations (BG1 to BG4) were fabricated by lyophilization and characterized in terms of physicochemical properties, antimicrobial activity, and cytocompatibility. Their therapeutic efficacy was further evaluated using an in vitro artificial wound model and a murine model of a DSB-infected wound. BG incorporation significantly influenced the scaffold properties. While BG1–BG3 maintained a comparable structure and mechanical integrity, BG4 exhibited a reduced pore size, swelling capacity, and mechanical resistance. All BG-loaded scaffolds reduced bacterial viability in vitro, with BG4 showing the strongest antimicrobial effect. In vivo, BG2 showed the most consistent overall performance, combining improved wound closure at day 6 with complete re-epithelialization at the endpoint. BG3 improved wound closure at day 6 but did not outperform it in re-epithelialization. In contrast, BG4 did not enhance healing despite its higher antimicrobial activity in vitro. These findings demonstrate that scaffold performance is governed by the interplay between extract loading and physicochemical properties, and that intermediate BG concentrations provide more favorable conditions for tissue repair than higher loadings. This work supports the potential of BG-loaded scaffolds as a therapeutic strategy for biofilm-infected chronic wounds.

Background: Chronic wounds represent a significant clinical challenge due to impaired healing and persistent inflammation. Bioactive scaffolds made from natural polymers combined with the hydroalcoholic extract of Buddleja globosa have emerged as promising alternatives for promoting effective tissue regeneration. Methods: A biocomposite scaffold composed of gelatin, chitosan, and hyaluronic acid, incorporating B. globosa extract, was fabricated. The material was evaluated for its physicochemical properties, biocompatibility with human neonatal dermal fibroblasts, and regenerative capacity in a chronic ischemic wound model in aged rats. Results: The composite exhibited a uniform, porous structure with an average pore size of approximately 200 μm and a high swelling capacity (>3000%) while preserving viscoelasticity with slight mechanical softening, thereby supporting optimal conditions for cell infiltration and exudate retention. The scaffold supported fibroblasts’ adhesion and proliferation, showing good biocompatibility. Formulations containing 0.04 and 0.08 mg/mL B. globosa extract significantly increased fibroblast viability at 14 days. Additionally, fibroblasts cultured on the biocomposite showed elevated secretion of proangiogenic vascular endothelial growth factor (VEGF) and CXC motif chemokine ligand 12 (CXCL12), compared to fibroblast monolayer cultures. In vivo, histological analysis revealed enhanced vascularization and reduced epithelial hyperplasia in wounds treated with the biocomposite, suggesting better tissue organization and maturation. Conclusion: Incorporating B. globosa extract into a gelatin–chitosan–hyaluronic acid scaffold offers bioactive properties that support angiogenesis and skin tissue regeneration. These results highlight the biocomposite’s potential as a multifunctional biomaterial with translational relevance for chronic wound therapy.

Chronic wounds are characterized by persistent inflammation and impaired fibroblast function, leading to defective tissue repair. Pannexin-1 (Panx1) channels regulate extracellular ATP release and purinergic signaling, processes implicated in inflammation and regeneration. Probenecid (PBN), a clinically approved Panx1 channels inhibitor, has emerged as a potential therapeutic modulator in chronic wounds; however, its compatibility with growth factor-mediated regenerative responses remains unclear. Here, we evaluated whether pharmacological inhibition of Panx1 channels alters βFGF-induced responses in human neonatal dermal fibroblasts (HDFn). Cells were treated with βFGF (10 ng/mL) in the presence or absence of PBN (200 μM), and migration, proliferation, extracellular matrix-related gene expression, extracellular ATP release, intracellular Ca²⁺ signaling, and Panx1 expression/localization were assessed. PBN did not significantly alter βFGF-induced migration, proliferation, or most extracellular matrix-related transcriptional responses, except for a further reduction in COL1A1 expression. In addition, βFGF did not modify PANX1 transcript levels, Panx1 protein abundance, or membrane localization. Although βFGF reduced extracellular ATP release and transiently modulated ATP-induced Ca²⁺ signaling, these effects occurred without detectable changes in Panx1 expression or localization. These findings support the compatibility of PBN with βFGF-driven regenerative responses in HDFn cells.