Metal-organic Zn-zoledronic acid and 1-hydroxyethylidene-1,1-diphosphonic acid nanostick-mediated zinc phosphate hybrid coating on biodegradable Zn for osteoporotic fracture healing implants

Abstract

Zn and its alloys are increasingly under consideration for biodegradable bone fracture fixation implants owing to their attractive biodegradability and mechanical properties. However, their clinical application is a challenge for osteoporotic bone fracture healing, due to their uneven degradation mode, burst release of zinc ions, and insufficient osteo-promotion and osteo-resorption regulating properties. In this study, a type of Zn²⁺ coordinated zoledronic acid (ZA) and 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP) metal-organic hybrid nanostick was synthesized, which was further mixed into zinc phosphate (ZnP) solution to mediate the deposition and growth of ZnP to form a well-integrated micro-patterned metal-organic/inorganic hybrid coating on Zn. The coating protected noticeably the Zn substrate from corrosion, in particular reducing its localized occurrence as well as suppressing its Zn²⁺ release. Moreover, the modified Zn was osteo-compatible and osteo-promotive and, more important, performed osteogenesis in vitro and in vivo of well-balanced pro-osteoblast and anti-osteoclast responses. Such favorable functionalities are related to the nature of its bioactive components, especially the bio-functional ZA and the Zn ions it contains, as well as its unique micro- and nano-scale structure. This strategy provides not only a new avenue for surface modification of biodegradable metals but also sheds light on advanced biomaterials for osteoporotic fracture and other applications. STATEMENT OF SIGNIFICANCE: Developing appropriate biodegradable metallic materials is of clinical relevance for osteoporosis fracture healing, whereas current strategies are short of good balance between the bone formation and resorption. Here, we designed a micropatterned metal-organic nanostick mediated zinc phosphate hybrid coating modified Zn biodegradable metal to fulfill such a balanced osteogenicity. The in vitro assays verified the coated Zn demonstrated outstanding pro-osteoblasts and anti-osteoclasts properties and the coated intramedullary nail promoted fracture healing well in an osteoporotic femur fracture rat model. Our strategy may offer not only a new avenue for surface modification of biodegradable metals but also shed light on better understanding of new advanced biomaterials for orthopedic application among others.

Keywords: Biodegradable metals; Bone formation and resorption; Metal-organic nanostick; Organic-inorganic hybrid coating; Osteoporotic bone fracture healing.