In vitro and in vivo characterization of pentaerythritol triacrylate-co-trimethylolpropane nanocomposite scaffolds as potential bone augments and grafts.

Cong Chen, Leah Garber, Mollie Smoak, Carmel Fargason, Thomas Scherr, Caleb Blackburn, Sasha Bacchus, Mandi J Lopez, John A Pojman, Fabio Del Piero, Daniel J Hayes

文献索引：Tissue Eng. Part A 21(1-2) , 320-31, (2015)

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摘要

A thiol-acrylate-based copolymer synthesized via an amine-catalyzed Michael addition was studied in vitro and in vivo to assess its potential as an in situ polymerizing graft or augment in bone defect repair. The blends of hydroxyapatite (HA) with pentaerythritol triacrylate-co-trimethylolpropane (PETA), cast as solids or gas foamed as porous scaffolds, were evaluated in an effort to create a biodegradable osteogenic material for use as a bone-void-filling augment. Osteogenesis experiments were conducted with human adipose-derived mesenchymal stromal cells (hASCs) to determine the ability of the material to serve as an osteoinductive substrate. Poly(ɛ-caprolactone) (PCL) composites PCL:HA (80:20) (wt/wt%) served as the control scaffold, while the experimental scaffolds included PETA:HA (100:0), (85:15), (80:20), and (75:25) composites (wt/wt%). The results indicate that PETA:HA (80:20) foam composites had higher mechanical strength than the corresponding porous PCL:HA (80:20) scaffolds made by thermo-precipitation method, and in the case of foamed composites, increasing HA content directly correlated with increased yield strength. For cytotoxicity and osteogenesis experiments, hASCs cultured for 21 days on PETA:HA scaffolds in stromal medium displayed the greatest number of live cells compared with PCL:HA composites. Moreover, hASCs cultured on foamed PETA:HA (80:20) scaffolds resulted in the greatest mineralization, increased alkaline phosphatase (ALP) expression, and the highest osteocalcin (OCN) expression after 21 days. Overall, the PETA:HA (80:20) and PETA:HA (85:15) scaffolds, with 66.38% and 72.02% porosity, respectively, had higher mechanical strength and cytocompatibility compared with the PCL:HA control. The results of the 6-week in vivo biocompatibility study using a posterior lumbar spinal fusion model demonstrate that PETA:HA can be foamed in vivo without serious adverse effects at the surgical site. Additionally, it was demonstrated that cells migrate into the interconnected pore volume and are found within centers of ossification.