Bioactive, "Self-Fitting" Shape Memory Polymer (SMP) Scaffolds to Treat Cranial Bone Defects
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Our research goal is the development of a bioactive, â€œself-fittingâ€ shape memory polymer (SMP)scaffold to repair confined cranial defects by associated bone marrow-derived mesenchymal stemcells (BMSCs). Autografts are associated with lengthy harvesting procedures, donor site morbidity as well asdifficulties in shaping and positioning the graft into the defect. Tissue engineering is a promising alternative butrequires a currently unmet need - a biomaterial scaffold which simultaneously provides: (1) the ability toconformally fit into an irregular defect to enhance osseointegration, (2) bioactivity, (3) osteoinductivityand (4) highly interconnected pores and controlled biodegradability necessary for cell migration, nutrientdiffusion and neotissue accumulation while avoiding brittle mechanical properties. The significance andinnovation of this approach is a new â€œself-fittingâ€, polydopamine-coated SMP scaffold design that achieves allof these properties. Developed by the PI, the proposed hybrid SMP scaffolds are comprised of an organicsegment [poly(Îµ-caprolactone), PCL] and an inorganic silicon-containing segment [polydimethylsiloxane,PDMS or poly(silyl ether), PSE]. The scaffold design meets key functional requirements: (1) Osseo-integration: The SMP scaffold will be â€œself-fittingâ€ as a result of its shape memory behavior, enablingconformal fitting into an irregular defect by brief exposure to warm saline and locking of the new temporaryshape upon cooling to body temperature. (2) Bioactivity and (3) Osteoinductivity: A nanothick, bioactivepolydopamine coating will be applied to the SMP scaffold pore surfaces to support progenitor cell osteogenesisas well the formation of hydroxyapatite necessary for osseointegration. (4) Interconnected Pores, ControlledBiodegradability, and Robust Mechanical Properties: The SMP scaffold fabrication strategy enables highporosities and pore interconnectivity while avoiding brittle mechanical behavior. The rate of scaffoldbiodegradation will be controlled by inorganic segment type (i.e. PDMS or PSE) and molecular weight (Mn) (i.e.crosslink density). The healing potential of SMP scaffolds will be evaluated in a critical size-rat calvarial modelusing histological testing, micro-CT and biomechanical testing. The team is comprised of experts in all key areas of the proposed work. Prof. Melissa Grunlan (PI) willlead efforts to prepare polydopamine-coated SMP scaffolds and uncoated controls (Aims 1-3). Prof. MariahHahn (Co-I) will lead in vitro tissue engineering studies with rat- and human-BMSCs incorporated into thescaffolds (Aim 2). Prof. Brian Saunders (Co-I) will implant cell-laden scaffolds into rat calvarial defects (Aim3). Prof. Michael Moreno will lead efforts to study biomechanical properties of scaffolds, native tissues andbone-graft constructs (Aims 1-3). Healing will be evaluated by histology/immunohistochemistry (Prof. RoyPool and Saunders, Co-Is), micro-CT (Saunders) and biomechanical tests (Moreno). Input will be provided bytwo craniofacial plastic surgeons, Drs. Raymond Harshbarger and Kevin Hopkins (consultants).