Shape Memory Polymer Scaffolds-Utility for In Vitro Osteogenesis of Canine Multipotent Stromal Cells

A biodegradable, shape memory polymer (SMP) scaffold based on poly(ε-caprolactone) (PCL) represents an attractive alternative therapy for the repair of critically sized bone defects given its ability to press-fit within irregular defects. Clinical translation of SMP scaffolds requires successful movement beyond proof-of-concept rodent studies through a relevant large-animal model and into the clinical setting. In addition to representing a clinical veterinary population, the canine species is a strong translational model for humans due to similarities in orthopedic disorders, biomechanics, and bone healing. The present study was performed to assess in vitro cytocompatibility and osteogenic differentiation of canine multipotent stromal cells (cMSCs) cultured on SMP scaffolds in preparation for future canine in vivo studies. Two different SMP scaffold compositions were utilized: a "PCL-only" scaffold prepared from PCL-diacrylate (PCL-DA) and a semi-interpenetrating network (semi-IPN) formed from PCL-DA and poly(L-lactic acid) (PCL:PLLA). The PCL:PLLA scaffolds degrade faster and are more mechanically rigid versus the PCL scaffolds. Canine bone marrow-derived MSCs (cMSCs) were evaluated in terms of attachment, proliferation, and osteogenic differentiation. cMSCs exhibited excellent cytocompatibility, attachment, and proliferation on both SMP scaffold compositions. PCL scaffolds were more conducive to both early- and late-stage in vitro osteogenesis of cMSCs versus PCL:PLLA scaffolds. However, cMSCs deposited mineralized extracellular matrix over 21 days when cultured on both SMP scaffold compositions. These results demonstrate that the SMP scaffolds are suitable for in vitro cMSC attachment, proliferation, and osteogenic differentiation, representing a significant step toward canine in vivo studies and potential translation to human patients.