Hydroxyapatite and Whitlockite Incorporated Cellulose Reinforced Poly-Caprolactone (PCL): Biomimetic Nanocomposites for Bone Tissue Engineering Applications

Structure-activity relationship of nano-hydroxyapatite (nHA) and whitlockite (nWH) nanocomposites using Poly-Caprolactone (PCL) and Microcrystalline cellulose (MCC) composite (95/5, 90/10, 85/15 wt%) for bone tissue regeneration is elucidated in this report. Morphology, crystallinity, thermal properties, degradation, mechanical properties, and In Vitro, In Vivo biocompatibility of composites were systematically evaluated. Briefly, nHA and nWH nanoparticles were synthesized by chemical precipitation and trisolvent systems, respectively. MCC 5 wt% in PCL matrix (PCL/MCC-5) showed enhanced mechanical strength, increased crystallinity, and porous morphology compared to virgin PCL. Morphological analysis of nHA and nWH reinforced PCL/MCC-5 composite revealed a reduction in the pore size. Structural analysis, XRD, FTIR, and DSC concluded that nHA and nWH addition (1–10 wt%) improved the crystallinity of the PCL/MCC-5 by acting as nucleating sites for polymer chains. The presence of Van der Waals forces of attraction caused an increase in crystallinity and a decrease in pore size. Mechanical testing revealed an increase in modulus by 113 times for 10 wt% nHA and 125 times increase on 10 wt% nWH loading compared to virgin PCL. In vitro cytocompatibility using Vero cell line showed ~ 88% cell viability for PCL/MCC-5 composite and ~ 94% for 5wt% and 10 wt% nHA loaded composite on day 7, which shows nanoparticles improved osteoconductive and osteinductivity of the composites. LIVE/DEAD assay with NIH3T3-L1 cell lines with 1% nHA showed the highest cell viability for all 3, 7, 14, and 21 days. In vivo trials with 10 wt% of nHA and nWH demonstrated full and thick muscle adherence and bio-interfacial affinity to the nanocomposites in comparison to virgin PCL. Our findings suggest that PCL/MCC composite with nHA and nWH may serve as a promising bone implant. Graphical Abstract