Repair and regeneration of critical sized defects via the utilization of polymeric bone graft substitutes are challenges. Here, we introduce radially and axially graded multizonal bone graft substitutes fabricated from polycaprolactone (PCL), and PCL biocomposites with osteoconductive particles, that is, hydroxyapatite (HA), and β-tricalcium phosphate (TCP). The novel bone graft substitutes should provide a greater degree of freedom to the orthopedic surgeon especially for repair of critically sized bone defects. The modulus of the graft substitute could be tailored in the axial direction upon the systematic variation of the HA/TCP concentration, while in the radial direction the bone graft substitute consisted of an outer layer with high stiffness, encapsulating a softer core with greater porosity. The biocompatibility of the bone graft substitutes was investigated using in vitro culturing of human bone marrow-derived stromal cells followed by the analysis of cell proliferation and differentiation rates. The characterization of the tissue constructs included the enzymatic alkaline phosphates (ALP) activity, microcomputed tomography imaging, and polymerase chain reaction analysis involving the expressions of bone markers, that is, Runx2, ALP, collagen type I, osteopontin, and osteocalcin, overall demonstrating the differentiation of bone marrow derived stem cells (BMSCs) via osteogenic lineage and formation of mineralized bone tissue.

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In vitro culturing and mechanical properties of three types of three-dimensional poly(caprolactone) scaffolds with interconnecting open-foam networks are reported. The scaffolds targeted bone tissue regeneration and were fabricated using twin screw extrusion and coextrusion techniques, for continuous mixing/shaping and formation of single or multilayers with distinct and tailorable porosities and pore sizes. Human fetal preosteoblastic cells, hFOB, were cultured on the extruded and coextruded scaffolds under osteogenic supplements and the samples of the resulting tissue constructs were removed and characterized for cell viability and proliferation using the MTS assay, differentiation, and mineralized matrix synthesis via the alkaline phosphatase, ALP, activity and Alizarin Red staining and cell migration using confocal microscopy and scanning electron microscopy. The hFOB cells formed a confluent lining on scaffold surfaces, migrated to the interior and generated abundant extracellular matrix after 2 weeks of culturing, indicative of the promise of such scaffolds for utilization in tissue engineering. The scaffolds and tissue constructs exhibited compressive fatigue behavior that was similar to that of cancellous bone, suggesting the suitability of their use as bone graft substitutes especially for repair of critical-sized defects or nonunion fractures.

A unitary bioresorbable cage/core bone graft substitute consisting of a stiff cage and a softer core with interconnected porosity is offered for spinal arthrodesis. Polycaprolactone, PCL, was used as the matrix and hydroxyapatite, HA, and β-tricalcium phosphate, TCP, were used in the formulation of the cage layer to impart modulus increase and osteoconductivity while the core consisted solely of PCL. The crystallinity, biodegradation rate (under accelerated conditions) and mechanical properties, i.e., the uniaxial compression, relaxation modulus upon step compression and cyclic compressive fatigue properties, of the co-extruded cage/core bone graft substitutes could be manipulated by changes in the concentration of HA/TCP in the cage layer. The cyclic fatigue behavior of the cage/core bone graft substitutes were also compared to the behavior of bovine vertebral cancellous bone characterized under similar testing conditions. The biocompatibility of the cage/core bone graft substitutes were assessed via in vitro culturing of human bone marrow derived stromal cells, BMSCs. The cell proliferation rates, time dependencies of the alkaline phosphates (ALP) activity and the expressions of bone markers, i.e., Runx2, ALP, collagen type I, osteopontin and osteocalcin, and the collected μ-CT images demonstrated the differentiation of BMSCs via osteogenic lineage and formation of mineralized bone tissue to indicate the biocompatibility of the cage/core bone graft substitutes.