Purpose <p>Chronic wounds impose a large socio-economic burden on both patients and healthcare providers. They result from altered cellular function and impaired tissue repair. Currently available treatments offer variable results, necessitating new therapeutic approaches. Biological scaffolds and cell-based therapies have shown promise in enhancing wound healing and regeneration. Off-the-shelf products and cell therapies that can be used immediately are an important translational factor.</p> Methods <p>This study evaluates the effect of Kerecis, a commercially available fish-skin-derived biological scaffold for mechanically isolated stromal vascular fraction (mSVF). A human dermal fibroblast monolayer was cultured for 24&#xa0;h in media containing 10% serum, then switched to starvation media. An indirect co-culture with Kerecis, mSVF, or Kerecis + mSVF was subsequently initiated over a 7-day period, maintaining culture in starvation media. The fibroblast monolayer without intervention served as control. Outcomes included cell viability, protein release, the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), as well as histological analysis.</p> Results <p>Overall cell viability increased significantly in both the mSVF and Kerecis + mSVF groups, when compared to the negative control. Protein release was highest in both Kerecis groups, on days 3 and 7. By means of ELISA, a significantly higher amount of VEGF was found to be present in both Kerecis groups, whereby the Kerecis + mSVF group demonstrated the highest release. Immunofluorescent staining did not confirm the presence of cells within the scaffold.</p> Conclusion <p>These results suggest that Kerecis alone and in combination with mSVF may support wound repair by extrinsic induction. The combination therapy of mSVF-loaded Kerecis may represent a promising approach to enhance regeneration in a clinical setting adhering to regulatory restrictions.</p> Lay Summary <p> Chronic wounds, such as diabetic ulcers or pressure sores, pose significant therapeutic challenges due to the impairment of cellular function and growth, which is characteristic of such conditions. In the present study, researchers evaluated a novel combination of two therapeutic interventions: a fish-skin graft product known as Kerecis® and a patient-derived cell mixture designated as stromal vascular fraction (SVF). In a laboratory setting, skin cells (fibroblasts) were cultivated under conditions of stress that simulated poor healing. It was observed that the combination of Kerecis® and SVF promoted the survival and activity of these cells. This approach has the potential to enhance the efficacy of future treatments for recalcitrant wounds by leveraging personalised and off-the-shelf components.</p> Description of Future Works <p> Subsequent studies will evaluate the long-term regenerative effects of Kerecis® and mSVF in more complex 3D wound models and in vivo systems. Further research will be conducted to investigate immunomodulatory interactions, establish optimal dosing strategies, and assess the feasibility of clinical translation for personalised wound care in patients with chronic or non-healing wounds.</p> Graphical Abstract <p></p>