Constructing Three-Dimensional Microenvironments Using Engineered Biomaterials for Bone and Cartilage Tissue Regeneration

Abstract

Osteoporosis is a growing challenge worldwide, especially in developing countries like India, where more than 15 million people have the disease every year. Current treatments for the disease are expensive and require extensive research to find a cost-effective tissue engineering-based solution. Osteoporosis-related long-term complications mainly affect the osteochondral region (bone and cartilage interface), and regeneration approaches become challenging due to limitations mimicking the in vivo microenvironment or lower angiogenesis. The regeneration and functional reconstruction of bone and cartilage are still major clinical challenges. The poor regeneration ability of cartilage, in comparison to the bone, hampers cartilage tissue engineering even further. The three-dimensional (3D) microenvironment provides in vivo mimetic signaling to target cells, thereby upregulating the repair process. Over the next 20 years, a massive increase in biomaterial science, mechanobiology, and manufacturing methods could benefit the repair of cartilage and bone tissue. Among tissue engineering methods, advancements in biomimetic scaffolds offer intriguing possibilities for establishing in vitro native tissue-like differentiation and efficient transplantation based on controlled 3D cellular connections and preserved cellular adhesion molecules. Recent advancements in biomaterial-based applications in bone and cartilage regeneration have been promising, and a few are under clinical trials. A cell-free scaffold enriched with biological cues (EVs and growth factors) and optimum physical cues (stiffness and porosity) for enhanced bone and cartilage regeneration would be advantageous. Hence, this chapter focuses on the bone/cartilage microenvironment and related cues required to reconstruct the 3D natural matrix using an engineered biomimetic scaffold system. The chapter summarizes the recent in vitro and in vivo developments at the cellular (stem cell) level. Furthermore, this chapter describes future approaches, including secretome/cell-free strategies, to reconstruct the native bone and cartilage tissue niche.