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.

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.

[Genetic testing and pedigree analysis for a case with intermediate α-thalassemia[--SEA/α90-92(AGCTTCGG)α]].

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with a rare non-deletional hemoglobin H disease (Hb H disease). METHODS: Peripheral venous blood samples of the proband and his parents were collected and subjected to routine blood testing, hemoglobin electrophoresis and screening for common mutations associated with thalassemia. Next generation sequencing was carried out to detect potential pathogenic variant, and candidate variant was verified by Sanger sequencing. RESULTS: The proband was found to harbor a rare HbA2: c272_279delAGCTTCGG variant, which compounded with southeast Asian type deletion of α-thalassemia (--SEA). The two mutations were respectively inherited from his mother and father. CONCLUSION: The rare HbA2: c.272_279delAGCTTCGG variant compounded with southeast Asian type α-thalassemia (--SEA) probably underlay the non-deletion Hb H in the proband. Above finding has enabled genetic counseling and prenatal diagnosis for this family.

Appropriately adapted properties of hot-extruded Zn-0.5Cu-xFe alloys aimed for biodegradable guided bone regeneration membrane application.

Appropriately adapted comprehensive mechanical properties, degradation behavior and biocompatibility are prerequisites for the application of Zn-based biodegradable implants. In this study, hot-extruded Zn-0.5Cu-xFe (x = 0.1, 0.2 and 0.4 wt%) alloys were fabricated as candidates for biodegradable materials for guided bone regeneration (GBR) membranes. The hot-extrusion process and Cu alloying were expected mostly to enhance the mechanical properties, and the Fe alloying was added mainly for regulating the degradation. The microstructure, mechanical properties and in vitro degradation behavior were systematically investigated. The ZnCuFe alloys were composed of a Zn matrix and FeZn13 phase. With increasing Fe content, a higher FeZn13 phase precipitation with larger particles was observed. Since elongation declined significantly until fracture with increasing Fe content up to 0.4 wt%, the ZnCuFe (0.2 wt%) alloy achieved a good balance between mechanical strength and ductility, with an ultimate tensile strength of 202.3 MPa and elongation at fracture of 41.2%. Moreover, the addition of Fe successfully accelerated the degradation of ZnCuFe alloys. The ZnCuFe (0.2 wt%) alloy showed relatively uniform corrosion in the long-term degradation test. Furthermore, extracts of the ZnCuFe (0.2 wt%) alloy showed no apparent cytotoxic effects against L929 fibroblasts, Saos-2 osteoblasts or TAg periosteal cells. The ZnCuFe (0.2 wt%) alloy exhibited the potential to inhibit bacterial adhesion of Streptococcus gordonii and mixed oral bacteria. Our study provides evidence that the ZnCuFe (0.2 wt%) alloy can represent a promising material for the application as a suitable GBR membrane.