Integrated approach in designing biphasic nanocomposite collagen/nBCP scaffolds with controlled porosity and permeability for bone tissue engineering.

The bone scaffold for tissue engineering should be biomimetic, particularly in simulating the porosity features of natural bony tissue including pore size, pore shape, pore distribution pattern, and porosity percentage. Control of these can impact the scaffold hydrophilicity and permeability, which in turn influence the protein adsorption, cellular functions, and vascularization process. Various methods have been investigated for control of porosity parameters; however, the field still suffers from major challenges, that is, inadequate control of porosity and hydrophilicity at different levels. In this study, we developed an integrated approach for generation and control of porosity within nanocomposite collagen/nanobiphasic calcium phosphate (collagen/nBCP) scaffold. A modified freeze-drying procedure was applied alongside a chemical foaming method exploring the ability of "Tween 20" as a potent biocompatible porogen. Several processing variables were also examined including; quenching rate (-18 and -80°C), collagen/nBCP ratio (92/8% and 85/15%), and Tween ratio (10%, 20%, and 30%). Detailed physicochemical and porosimetry analysis confirmed the ability of Tween to actively modify the scaffold permeability and pore size by increasing the range of pore size while quenching rate mostly influenced the pore shape, and collagen/nBCP ratio affected total porosity and roughness. The collagen/nBCP ratio of 92/8% treated with low Tween ratios (10% and 20%) and exposed to -80°C quenching rate displayed more favorable physicochemical behavior, significantly higher permeability, a gradient porosity, and better in vitro performances. The proposed technique in this study provides an insight into the production of customized scaffolds for various tissue engineering applications.