Controlled release of resveratrol from a composite nanofibrous scaffold: Effect of resveratrol on antioxidant activity and osteogenic differentiation.

Biocompatibility, mechanical strength, and osteogenesis properties of three-dimensional scaffolds are critical for bone tissue engineering. In addition, reactive oxygen species accumulate around bone defects and limit the activities of surrounding cells and bone formation. Therefore, the presence of an antioxidant in a bone tissue scaffold is also essential to address this issue. This study aimed to evaluate a composite nanofibrous scaffold similar to the natural extracellular matrix with antioxidant and osteogenic properties. To this end, polylactic acid (PLA)/organophilic montmorillonite (OMMT)/resveratrol (RSV) nanofibers were fabricated using the electrospinning method and characterized. RSV was used as an antioxidant, which promotes osteogenic differentiation, and OMMT was used as a mineral phase to increase the mechanical strength and control the release of RSV. The scaffolds' antioxidant activity was measured using DPPH assay and found 83.75% for PLA/OMMT/RSV nanofibers. The mechanical strength was increased by adding OMMT to the neat PLA. The biocompatibility of the scaffolds was investigated using an MTT assay, and the results did not show any toxic effects on human adipose mesenchymal stem cells (hASCs). Moreover, the Live/Dead assay indicated the appropriate distribution of live cells after 5 days. Cell culture results displayed that hASCs could adhere and spread on the surface of composite nanofibers. Meanwhile, the level of alkaline phosphatase, osteocalcin, and osteopontin was increased for hASCs cultured on the PLA/OMMT/RSV nanofibrous scaffold. Therefore, this study concludes that the RSV-loaded composite nanofibers with antioxidant and osteogenesis properties and appropriate mechanical strength can be introduced for bone tissue regeneration applications.

Fabrication of oxygen and calcium releasing microcarriers with different internal structures for bone tissue engineering: Solid filled versus hollow microparticles.

The survival of cells in a three-dimensional scaffold until the ingrowth of blood vessels is an important challenge in bone tissue engineering. Oxygen generating biomaterials can provide the required oxygen and prevent hypoxia in a tissue-engineered scaffold. In this study, poly (L-lactic acid) (PLLA) microspheres loaded with synthesized calcium peroxide (CPO) nanoparticles were fabricated using two different methods, which resulted in hollow and solid filled internal structures. Catalase enzyme was grafted onto the microsphere surfaces to accelerate the conversion of hydrogen peroxide (H2O2) to oxygen and prevent the accumulation of H2O2 and cell damages. CPO loaded PLLA microspheres-graft-catalase could provide dissolved oxygen and calcium ions in release media up to 15 days. The oxygen release profile of solid filled microspheres was more sustained than the hollow structure, and the amount of calcium ions was higher for hollow microspheres due to the high loading content of CPO. MTT assay showed that CPO loaded PLLA microspheres without catalase exhibited a decrease in the cell viability below 75 %, and catalase grafting could prevent cytotoxicity. Human adipose-derived mesenchymal stem cells (hASCs) could adhere to the microsphere surfaces, maintain their morphology, and spread well. Based on these results, CPO loaded PLLA microspheres-graft-catalase, with the ability of cell carrying and controlled release of oxygen and calcium ions, can be a promising injectable cell microcarrier system for regeneration of bone tissue defects.