Early tissue response to citric acid-based micro- and nanocomposites

Composites based on calcium phosphates and biodegradable polymers are desirable for orthopedic applications because of their potential to mimic bone. Herein, we describe the fabrication, characterization, and in vivo response of novel citric acid-based microcomposites and nanocomposites. Poly(1,8-octanediol-co-citrate) (POC) was mixed with increasing amounts of hydroxyapatite (HA) nanoparticles or microparticles (up to 60 wt %), and the morphology and mechanical properties of the resulting composites were assessed. To investigate tissue response, nanocomposites, microcomposites, POC, and poly(L-lactide) were implanted in osteochondral defects in rabbits and harvested at 6 weeks for histological evaluation. Scanning electron microscopy confirmed increased surface roughness of microcomposites relative to nanocomposites. The mechanical properties of both types of composites increased with increasing amounts of HA (8-328 MPa), although nanocomposites with 60 wt % HA displayed the highest strength and stiffness. Based on tissue-implant interfacial assessments, all implants integrated well with the surrounding bone and cartilage with no evidence of inflammation. Both nanocomposites and microcomposites supported bone remodeling; however, nanocomposites induced more trabecular bone formation at the tissue-implant interface. The mechanical properties of citric acid-based composites are within the range of human trabecular bone (1-1524 MPa, 211 ± 78 MPa mean modulus), and tissue response was dependent on the size and content of HA, providing new perspectives of design and fabrication criteria for orthopedic devices such as interference screws and fixation pins.