Abstract
The ability to use the body’s resources to promote wound repair is increasingly becoming an interesting area of regenerative medicine research. Here, we tested the effect of topical application of blood-derived hypoxia preconditioned serum (HPS) on wound healing in a murine wound model. Alginate hydrogels loaded with two different HPS concentrations (10 and 40%) were applied topically on full-thickness wounds created on the back of immunocompromised mice. We achieved a significant dose-dependent wound area reduction after 5 days in HPS-treated groups compared with no treatment (NT). On average, both HPS-10% and HPS-40% -treated wounds healed 1.4 days faster than NT. Healed tissue samples were investigated on post-operative day 15 (POD 15) by immunohistology and showed an increase in lymphatic vessels (LYVE-1) up to 45% with HPS-40% application, while at this stage, vascularization (CD31) was comparable in the HPS-treated and NT groups. Furthermore, the expression of proliferation marker Ki67 was greater on POD 15 in the NT-group compared to HPS-treated groups, in accordance with the earlier completion of wound healing observed in the latter. Collagen deposition was similar in all groups, indicating lack of scar tissue hypertrophy as a result of HPS-hydrogel treatment. These findings show that topical HPS application is safe and can accelerate dermal wound healing in mice.
Highlights
Experimental Plastic Surgery, Clinic for Plastic, Reconstructive and Hand Surgery, Klinikum Rechts der Isar, Department of Plastic, Reconstructive and Aesthetic Surgery, Isar Klinikum, D-80331 Munich, Germany; Department of Trauma Surgery, Orthopedics and Plastic Surgery, Universitätsmedizin Göttingen, Abstract: The ability to use the body’s resources to promote wound repair is increasingly becoming an interesting area of regenerative medicine research
LYVE-1 was augmented in the subcutaneous layer of hypoxia preconditioned serum (HPS)-40% treated wounds compared to no treatment (NT) (p = 0.01), indicating superior lymphangiogenesis with a higher concentration of HPS application (Figure 3)
The epidermis thickness was determined by software measurement throughout the healed tissue, with no significant differences between treatment and no treatment groups
Summary
We achieved a significant dose-dependent wound area reduction after 5 days in HPS-treated groups compared with no treatment (NT). On average, both HPS-10% and HPS-40% -treated wounds healed 1.4 days faster than NT. Collagen deposition was similar in all groups, indicating lack of scar tissue hypertrophy as a result of HPS-hydrogel treatment. These findings show that topical HPS application is safe and can accelerate dermal wound healing in mice. In the US alone, 3 to 6 million people suffer from non-healing wounds [3], with an overall cost to the American healthcare system of around three billion dollars a year [4,5]. As we come to understand wound healing processes in greater depth, we acknowledge that this is a complex system of biological interactions that requires the coordination of several cell types, intra- and extracellular mechanisms and signaling pathways
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