Long-term in vivo response to citric acid-based nanocomposites for orthopaedic tissue engineering

The disadvantages of current bone grafts have triggered the development of a variety of natural and synthetic bone substitutes. Previously, we have described the fabrication, characterization, and short-term tissue response of poly(1,8-octanediol-co-citrate) (POC) with 60 weight % hydroxyapatite nanocrystals (POC-HA) at 6 weeks. In order to better understand the clinical potential, longer term effects, and the biodegradation, biocompatibility, and bone regenerative properties of these novel nanocomposites, POC-HA, POC, and poly-L-lactide (PLL) were implanted in osteochondral defects in a rabbit model and assessed at 26 weeks. Explants were stained with Masson Goldner Trichrome and the fibrous capsule and tissue ingrowth measured. In addition, the bone-implant and bone-cartilage response of POC-HA, POC, and PLL were assessed through histomorphometry and histological scoring. Upon histological evaluation, both POC-HA and POC implants were biocompatible, but PLL implants were surrounded by a layer of leukocytes at 26 weeks. In addition, due to the degradation properties of POC-HA, tissue grew into the implant and had the highest area of tissue ingrowth although not statistically significant. Histomorphometric analyses supported a similar osteoid, osteoblast, and trabecular bone surface area among all implants although the fibrous capsule thickness was the largest for POC. Moreover, histological scoring demonstrated comparable scores among all three groups of the articular cartilage and subchondral bone. This study provides the long-term bone and cartilage response of novel, citric acid-based nanocomposites and their equivalence to FDA-approved biomaterials. Furthermore, we provide new insights and further discussion of these nanocomposites for orthopaedic applications.