Unitary multi-zonal bioresorbable bone graft substitutes coextruded from polycaprolactone and its biocomposites targeting bone repair and regeneration

Repair and regeneration of bone related defects via the utilization of polymeric bone graft substitutes is a challenge. The native bone tissue itself is an anatomically complex structure with significant variations in properties among its transverse and longitudinal directions. For bone graft substitutes to be effective in bone regeneration, it is desirable to mimic such complex gradations found in bone tissue, i.e., desirable for bone graft substitutes to exhibit three-dimensional distributions in composition, structure and properties. Here a new co-extrusion based technology base was first developed for the shaping of multi-zonal bone graft substitutes which can also be graded in the axial direction. The first-generation bone graft substitutes were constituted of bioresorbable poly(caprolactone) with distinct and tailorable porosities and pore sizes changing along the transverse to flow direction in conjunction with formation of different co-axial layers. The second-generation graft substitutes involved a cage/core structure and were incorporated with calcium phosphate ceramic particles, hydroxyapatite (HA) and beta-tricalcium phosphate (TCP), to impart modulus increase for load-bearing applications as well as osteoconductive environment for faster bone regeneration in the defect site. Finally, the third-generation bone graft substitutes with radial and axial gradations were designed in the pursuit of mimicking the native cortical/cancellous bone structure. The mechanical performance of the bone graft substitutes were characterized under uniaxial and cyclic fatigue compression. Their biocompatibility of the bone graft substitutes were assessed by seeding the first-generation bone graft substitutes with human fetal pre-osteoblastic cells. The second and third-generation bone graft substitutes were seeded with human bone marrow-derived stromal cells. The proliferation and differentiation of the stem cells were characterized as a function of culturing time using polymerase chain reaction, micro computed tomography, ALP along with SEM and EDX. All bone graft substitutes supported the cell attachment, proliferation and differentiation into bone tissue.