Zein-based injectable biomaterial and angiogenic activity through peptides produced by enzymatic degradation

Abstract

Injectable biomaterials are gaining attention due to minimal invasiveness and precise implantation in deep anatomical locations. For tissue regeneration, controlling the degradation and improving vascularization are still the key issues to be resolved. Moreover, for protein-based biomaterials, immune response should be specially considered, although they have advantages such as biodegradability, their degraded products have innate bioactivity and can be utilized by our body. Zein, a plant protein, has been explored for biomedical applications. Recently, we have reported zein gel as a 3D printing ink for drug delivery systems. In this study, we extended the application of zein gel as an injectable biomaterial. Zein gels showed shear-thinning property and tunable yield stress, which is essential for injectability and shape adaptability. Polyvinylpyrrolidone (PVP) was added to the gel to accelerate the degradation and subsequently generate more bioactive peptides for their anti-inflammatory and angiogenic functions as evidenced by in vitro evaluation. Animal experiment using Sprague Dawley (SD) rats also showed a positive angiogenic response after subcutaneous implantation of zein gels with PVP. Bioactive peptides produced from zein degradation were responsible for the angiogenic response that was validated by adding zein degraded products to the gel. Overall, zein gel was proven a promising injectable biomaterial that can fill tissue defect and improve tissue regeneration with controllable degradation rate. Moreover, the enzyme-treated zein hydrolysates can be used as additives with angiogenic activity.