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Chronic wounds are characterized by both decreased collagen deposition and increased collagen breakdown. It is reasonable to hypothesize that exogenous collagen can potentially promote wound healing by reducing degradation enzymes in the wound environment and disrupting the cycle of chronicity. Therefore, this study aimed to develop an optimal combination of fish collagen (FCOL), sodium alginate (SA), and hyaluronic acid (HA) loaded with bovine serum albumin (BSA) as a model protein fabricated as lyophilized scaffolds. The effects of sodium alginate (SA#) with higher mannuronic acid (M) were compared to sodium alginate (SA*) with higher guluronic acid (G). The SA* with higher G resulted in elegant scaffolds with hardness ranging from 3.74 N–4.29 N that were able to withstand the external force due to the glycosidic bonds in guluronic acid. Furthermore, the high G content also had a significant effect on the pore size, pore shape, and porosity. The water absorption (WA) ranged from 380–1382 (%) and equilibrium water content (EWC) 79–94 (%) after 24 h incubation at 37 °C. The SA* did not affect the water vapor transmission rate (WVTR) but incorporating BSA significantly increased the WVTR making these wound dressing scaffolds capable of absorbing about 50% exudate from a heavily exuding chronic wound. The protein released from the composite systems was best explained by the Korsmeyer–Peppas model with regression R2 values ranging from 0.896 to 0.971 and slope or n &lt; 0.5 indicating that the BSA release mechanism was governed by quasi-Fickian diffusion. Cell viability assay showed that the scaffolds did not inhibit the proliferation of human dermal fibroblasts and human epidermal keratinocytes, and are therefore biocompatible. In vitro blood analysis using human whole blood confirmed that the BSA-loaded SA*:FCOL:HA scaffolds reduced the blood clotting index (BCI) by up to 20% compared to a commercially available sponge for chronic wounds. These features confirm that SA*:FCOL:HA scaffolds could be applied as a multifunctional wound dressing.

Composite Fish Collagen-Hyaluronate Based Lyophilized Scaffolds Modified with Sodium Alginate for Potential Treatment of Chronic Wounds