Physicochemical properties and angiogenic potential of whey protein isolate hydrogels modified with heparin or tinzaparin

Pawlak-Likus, Zuzanna and Baines, Daniel and Tavernaraki, Nikoleta and Platania, Varvara and Smith, Alan and Chatzinikolaidou, Maria and Domalik-Pyzik, Patrycja and Douglas, Timothy (2025) Physicochemical properties and angiogenic potential of whey protein isolate hydrogels modified with heparin or tinzaparin. Journal of Polymers and the Environment. ISSN 1566-2543 (In Press)

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Abstract

A key challenge in tissue engineering is developing functional tissues that can effectively mimic the structure and function of natural tissues. This involves creating scaffolds that support cell proliferation, and differentiation. This research aimed to develop hydrogels as scaffolds that could be utilised in tissue engineering, particularly in applications that require angiogenesis. Whey protein isolate (WPI) has been employed as the main hydrogel component, as WPI hydrogels have been investigated for possible applications in bone tissue engineering. Heparin (HP) and tinzaparin (TP) were selected as additives, as they enhance cellular growth and exhibit anti-inflammatory properties. Nine different compositions were created, each with varying percentages of the additives, a control sample containing pure WPI, and samples with HP or TP at 2.5%, 5%, 7.5%, and 10% concentrations. The mechanical tests showed compressive moduli in the range of 430-620 kPa for the modified hydrogels and indicated that a 5% content of HP or TP is optimal in terms of mechanical characteristics. The highest swelling ratios of approximately 13% and 16%, respectively were noted in both modified groups (TP and HP) at the 7.5% concentration. HP 2.5% demonstrated the highest cytocompatibility among all HP concentrations, including the WPI control, while TP 10% exhibited greater cytocompatibility than other TP concentrations, also surpassing the WPI control. All hydrogels with additives enhanced cell attachment compared to the WPI control, indicating better cytocompatibility. The morphology visualization of DPSCs indicated no significant differences between the four HP or TP concentrations. TP 10% showed the most promising results in angiogenic differentiation potential tests in vitro, suggesting this composition should be studied further.