Enhanced osteogenesis on proantocyanidin-loaded date palm endocarp cellulosic matrices: A novel sustainable approach for guided bone regeneration

Developing inexpensive, biocompatible natural scaffolds that can support the differentiation and proliferation of stem cells has been recently emphasized by the research community to faster obtain the FDA approvals for regenerative medicine. In this regard, plant-derived cellulose materials are a novel class of sustainable scaffolding materials with high potentials for bone tissue engineering (BTE). However, low bioactivity of the plant-derived cellulose scaffolds restricts cell proliferation and cell differentiation. This limitation can be addressed though surface-functionalization of cellulose scaffolds with natural antioxidant polyphenols, e.g., grape seed proanthocyanidin (PCA)-rich extract (GSPE). Despite the various merits of GSPE as a natural antioxidant, its impact on the proliferation and adhesion of osteoblast precursor cells, and on their osteogenic differentiation is an as-yet unknown issue. Here, we investigated the effects of GSPE surface functionalization on the physicochemical properties of decellularized date (Phoenix dactyliferous) fruit inner layer (endocarp) (DE) scaffold. In this regard, various physiochemical characteristics of the DE-GSPE scaffold such as hydrophilicity, surface roughness, mechanical stiffness, porosity, and swelling, and biodegradation behavior were compared with those of the DE scaffold. Additionally, the impact of the GSPE treatment of the DE scaffold on the osteogenic response of human mesenchymal stem cells (hMSCs) was thoroughly studied. For this purpose, cellular activities including cell adhesion, calcium deposition and mineralization, alkaline phosphatase (ALP) activity, and expression levels of bone-related genes were monitored. Taken together, the GSPE treatment enhanced the physicochemical and biological properties of the DE-GSPE scaffold, thereby raising its potentials as a promising candidate for guided bone regeneration.