Cell-Instructive Mineralized Microenvironment Regulates Osteogenesis: A Growing SYMBIOSIS of Cell Biology and Biomaterials Engineering in Bone Tissue Regeneration

One of the objectives of bone tissue engineering is to produce scaffolds that are biocompatible, osteoinductive, and mechanically equivalent to the natural extracellular matrix of bone in terms of structure and function. Reconstructing the osteoconductive bone microenvironment into a scaffold can attract native mesenchymal stem cells and differentiate them into osteoblasts at the defect site. The symbiotic relationship between cell biology and biomaterial engineering could result in composite polymers containing the necessary signals to recreate tissue- and organ-specific differentiation. In the current work, drawing inspiration from the natural stem cell niche to govern stem cell fate, the cell-instructive hydrogel platforms were constructed by engineering the mineralized microenvironment. This work employed two different hydroxyapatite delivery strategies to create a mineralized microenvironment in an alginate–PEGDA interpenetrating network (IPN) hydrogel. The first approach involved coating of nano-hydroxyapatite (nHAp) on poly(lactide- co -glycolide) microspheres and then encapsulating the coated microspheres in an IPN hydrogel for a sustained release of nHAp, whereas the second approach involved directly loading nHAp into the IPN hydrogel. This study demonstrate that both direct encapsulation and a sustained release approach showed enhanced osteogenesis in target-encapsulated cells; however, direct loading of nHAp into the IPN hydrogel increased the mechanical strength and swelling ratio of the scaffold by 4.6-fold and 1.14-fold, respectively. In addition, the biochemical and molecular studies revealed improved osteoinductive and osteoconductive potential of encapsulated target cells. Being less expensive and simple to perform, this approach could be beneficial in clinical settings.