Interfacial Zinc Phosphate is the Key to Controlling Biocompatibility of Metallic Zinc Implants

Abstract

Recently emerged metallic zinc (Zn) is a new generation of promising candidates for bioresorbable medical implants thanks to its essential physiological relevance, mechanical strength, and more matched degradation pace to that of tissue healing. Zn‐based metals exhibit excellent biocompatibility in various animal models. However, direct culture of cells on Zn metals yields surprisingly low viability, indicating high cytotoxicity of Zn. This contradicting phenomenon should result from the different degradation mechanisms between in vitro and in vivo. To solve this puzzle, the roles of all major players, i.e., zinc phosphate (ZnP), zinc oxide (ZnO), zinc hydroxide (Zn(OH) 2 ), pH, and Zn 2+ , which are involved in the degradation process are examined. Data shows that ZnP, not ZnO or Zn(OH) 2 , significantly enhances its biocompatibility. The mild pH change during degradation also has no significant impact on cell viability. Collectively, ZnP appears to be the key to controlling the biocompatibility of Zn implants and could be applied as a novel surface coating to improve biocompatibility of different implants.

Calcium phosphate coatings enhance biocompatibility and degradation resistance of magnesium alloy: Correlating in vitro and in vivo studies

“…On the other hand, biocompatibility is somehow easier to be predicted using in vitro cell-based testing. It is recommended to use a 6–10 times dilution of extracts for in vitro indirect cytotoxicity test for Mg and other biodegradable metals [ [48] , [49] , [50] , [51] ]. There are also some sophisticated setups and methods suggested to be used in vitro to predict the blood compatibility of biodegradable metals [ [52] , [53] , [54] ].…”

Biofunctionalization of metallic implants by calcium phosphate coatings

“…To achieve the biocompatibility and biofunctions on the implant materials, surface biofunctionalization is one of the easiest ways to change the surface properties which can improve the surface bioactivity, eliminate or control the degradation rate, and prevent implant-related infections, etc. [ [16] , [17] , [18] , [19] ]. For example, surface modification with appropriate coatings can create a favorable surface morphology for the adsorption of proteins in the interactions with biological fluids, and thus promote the cell–extracellular matrix (ECM) interactions and the production of growth factors [ 20 , 21 ].…”

Interleukin-4 assisted calcium-strontium-zinc-phosphate coating induces controllable macrophage polarization and promotes osseointegration on titanium implant

“…It has also been reported that the Sr-loaded phase-transited lysozyme (PTL) coating invokes greater osteogenesis ability by its effects on the immune environment due to the constant release of Sr ions directly at the implant-tissue interface [ 38 ]. Su et al [ 39 ] discovered that the Zn ion that exist in the form of zinc phosphate, plays a key role in improving osseointegration and immune regulation. The immune microenvironment produced by the micro/nanostructured TiO 2 /ZnO coating also showed better capacity to promote osteogenesis macroporous than the TiO 2 coating, which indicated that Zn ion plays an important role in osteoimmunomodulation [ 40 ].…”