Diamond-like carbon coating and surface grafting of osteoprotegerin and alendronate on polyetheretherketone to ameliorate the mechanical performance and osseointegration simultaneously

The strength and integrity of our bones depends on maintaining a delicate balance between bone resorption by osteoclasts and bone formation by osteoblasts. As we age or as a result of disease, this delicate balancing act becomes tipped in favor of osteoclasts so that bone resorption exceeds bone formation, rendering bones brittle and prone to fracture. A better understanding of the biology of osteoclasts and osteoblasts is providing opportunities for developing therapeutics to treat diseases of bone. Drugs that inhibit the formation or activity of osteoclasts are valuable for treating osteoporosis, Paget's disease, and inflammation of bone associated with rheumatoid arthritis or periodontal disease. Far less attention has been paid to promoting bone formation with, for example, growth factors or hormones, an approach that would be a valuable adjunct therapy for patients receiving inhibitors of bone resorption.

Since the 1980s, polyaryletherketones (PAEKs) have been increasingly employed as biomaterials for trauma, orthopedic, and spinal implants. We have synthesized the extensive polymer science literature as it relates to structure, mechanical properties, and chemical resistance of PAEK biomaterials. With this foundation, one can more readily appreciate why this family of polymers will be inherently strong, inert, and biocompatible. Due to its relative inertness, PEEK biomaterials are an attractive platform upon which to develop novel bioactive materials, and some steps have already been taken in that direction, with the blending of HA and TCP into sintered PEEK. However, to date, blended HA-PEEK composites have involved a trade-off in mechanical properties in exchange for their increased bioactivity. PEEK has had the greatest clinical impact in the field of spine implant design, and PEEK is now broadly accepted as a radiolucent alternative to metallic biomaterials in the spine community. For mature fields, such as total joint replacements and fracture fixation implants, radiolucency is an attractive but not necessarily critical material feature.

A novel secreted glycoprotein that regulates bone resorption has been identified. The protein, termed Osteoprotegerin (OPG), is a novel member of the TNF receptor superfamily. In vivo, hepatic expression of OPG in transgenic mice results in a profound yet nonlethal osteopetrosis, coincident with a decrease in later stages of osteoclast differentiation. These same effects are observed upon administration of recombinant OPG into normal mice. In vitro, osteoclast differentiation from precursor cells is blocked in a dose-dependent manner by recombinant OPG. Furthermore, OPG blocks ovariectomy-associated bone loss in rats. These data show that OPG can act as a soluble factor in the regulation of bone mass and imply a utility for OPG in the treatment of osteoporosis associated with increased osteoclast activity.