Biomineralized hydroxyapatite nanoclay composite scaffolds with polycaprolactone for stem cell‐based bone tissue engineering

Nanoclay modified with unnatural amino acid was used to design a nanoclay‐hydroxyapatite (HAP) hybrid by mineralizing HAP in the nanoclay galleries mimicking biomineralization. This hybrid ( in situ HAPclay) was used to fabricate polycaprolactone (PCL)/ in situ HAPclay films and scaffolds for bone regeneration. Cell culture assays and imaging were used to study interactions between human mesenchymal stem cells (hMSCs) and PCL/ in situ HAPclay composites (films and scaffolds). SEM imaging indicated MSC attachment, formation of mineralized extracellular (ECM) on PCL/ in situ HAPclay films, and infiltration of MSCs to the interior of PCL/ in situ HAPclay scaffolds. Mineralized ECM was formed by MSCs without use of osteogenic supplements. AFM imaging performed on this in vitro generated mineralized ECM on PCL/ in situ HAPclay films revealed presence of components (collagen and mineral) of hierarchical organization reminiscent of natural bone. Cellular events observed during two‐stage seeding experiments on PCL/ in situ HAPclay films indicated similarities with events occurring during in vivo bone formation. PCL/ in situ HAPclay films showed significantly increased (100–595% increase in elastic moduli) nanomechanical properties and PCL/ in situ HAPclay scaffolds showed increased degradation. This work puts forth PCL/ in situ HAPclay composites as viable biomaterials for bone tissue engineering. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 2077–2101, 2015.