Bioactive ulvan creams from ulva lactuca extraction-process-dependent and in vivo wound-healing efficacy

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Abstract The aim of this study was to evaluate the in vivo wound-healing efficacy of novel ulvan-based creams formulated at 7% (weight/weight) ulvan extracted from Ulva lactuca . Ulvan was extracted using two acidic procedures CA1 (80 °C, pH 2) and CA2 (90 °C, pH 1.5)) and one enzymatic–chemical procedure (EE), and subsequently incorporated into topical cream formulations. The wound-healing activity was assessed in a rat excisional wound model over 14 days period using macroscopic evaluation, wound contraction measurement, and histological analysis. The ulvan creams (CA1, CA2, and EE) exhibited significant wound-healing activity, producing clean, healthy wounds with a homogeneous appearance and promoting remarkable tissue repaid, achieving up to 99% wound closure after 14 days of treatment. Among the extraction procedures evaluated, the CA1-based cream achieved the highest wound appearance scores and demonstrated the greatest ability to stimulate collagen deposition, fibroblast proliferation, and tissue regeneration. Furthermore, treatment with the CA1 cream promoted the formation of a well-structured re-epithelialized epidermal layer. It also enhanced the proliferation of healthy surrounding cells at the wound borders and restored a well-defined boundary between the epidermis and dermis. The superior healing performance of the CA1-based cream was attributed to the combination of low- and high-molecular-weight ulvan fractions, its high contents of uronic acid, rhamnose, and xylose, and its favorable physicochemical properties, which collectively enhanced the affinity for and delivery of bioactive compounds to the wound tissue. Therefore, the CA1-based cream represents a promising candidate for the development of advanced wound-healing technologies systems.