Search

In this work, rapamycin-eluting poly (d, l-lactic acid) coating (PDLLA/RAPA) was prepared on biodegradable Mg-Nd-Zn-Zr alloy (JDBM) for both in vitro and in vivo investigation of the degradation behaviors of the magnesium alloy stent platform. Electrochemical tests and hydrogen evolution test demonstrated significant in vitro protection of the polymeric coating against magnesium degradation both in short and long term. The 3-month in vivo study on the RAPA-eluting JDBM stent implanted into porcine coronary arteries confirmed its favorable safety, and in the meanwhile revealed similar neointima proliferation compared to the second generation DES Firebird 2 with no occurrence of adverse complications. Moreover, Micro-CT examination combined with IVUS and OCT detection indicated a remarkably lower degradation rate and prolonged radial supporting duration of the drug-eluting JDBM stent as compared to the bare, attributable to the protection of the coating in vivo. Hence, rapamycin-eluting JDBM stents exhibit great potential for clinical application.

To understand the possible influence of substrate degradation on the drug-loading system of magnesium alloy-based drug-eluting stents, a rapamycin drug-loading poly(lactic-co-glycolic acid) coating was prepared on Mg-Nd-Zn-Zr stents for a systematic investigation in a phosphate buffer system. Mg degradation accelerated the drug release kinetics prominently, which was mainly attributed to H2 evolution in the diffusion-controlled phase while thereafter to PLGA erosion. Although physiochemical stability of the released rapamycin was partially deteriorated by magnesium degradation, the drug-loading system on magnesium substrates exhibited a more potent long-term inhibition on smooth muscle cell proliferation in vitro as compared to drug-loaded stainless steel.

Biodegradable magnesium alloy stents exhibit deficient corrosion period for clinic applications, making the protective polymer coating more crucial than drug-eluting stents with the permanent metal scaffold. We implemented a cohesive method based on a finite element analysis method to predict the integrity of adhesive between coating and stent during the crimping and deployment. For the first time, the three-dimensional quantitative modeling reveals the process of polymer coating delamination and stress concentration. The fracture and microcracks of coatings were consistent with the simulation result, confirmed by the scanning electron microscopy observation. Moreover, we analyzed four possible factors, i.e., stent design, strut material, coating polymer, and thickness of the coating, affecting the stent-coating damage and the distribution of the stress in coatings. Mg-Nd-Zn-Zr alloy with lower yield strength performed a more uniform strain distribution and more favorable adhesion of the coating than the commercial magnesium alloy AZ31. Shape optimization of stent design improves the strain and stress distribution of coating remarkably, avoiding coating delamination. Additionally, PLGA coating with lower elastic modulus and yield strength tends to follow the deformation of the stent better and to adhere on the surface more tightly, compared to PLLA polymer. A reduction in coating thickness and an increase in the strength of stent-coating interface improve the resistance to delamination. Our framework based on cohesive method provides an in-depth understanding of stent-coating damage and shows the way of computational analyses could be implemented in the design of coated biodegradable magnesium stents.

Recently magnesium and its alloys have been proposed as a promising next generation orthopedic implant material, whereas the poor corrosion behavior, potential cytotoxicity, and the lack of efficient drug delivery system have limited its further clinical application, especially for the local treatment of infections or musculoskeletal disorders and diseases. In this study, we designed and developed a multifunctional bilayer composite coating of poly(lactic acid)/brushite with high interfacial bonding strength on a Mg-Nd-Zn-Zr alloy, aiming to improve the biocorrosion resistance and biocompatibility of the magnesium-based substrate, as well as to further incorporate the biofunctionality of localized drug delivery. The composite coating consisted of an inner layer of poly(lactic acid) serving as a drug carrier and an outer layer composed of brushite generated through chemical solution deposition, where a facile pretreatment of UV irradiation was applied to the poly(lactic acid) coating to facilitate the heterogeneous nucleation of brushite. The in vitro degradation results of electrochemical measurements and immersion tests indicated a considerable reduction of magnesium degradation provided the composite coating. A systematic investigation of cellular response with cell viability, adhesion, and ALP assays confirmed the coated Mg alloy induced no toxicity to MC3T3-E1 osteoblastic cells but rather fostered cell attachment and proliferation and promoted osteogenic differentiation, revealing excellent biosafety and biocompatibility and enhanced osteoinductive potential. An in vitro drug release profile of paclitaxel from the composite coating was monitored with UV-vis spectroscopy, showing an alleviated initial burst release and a sustained and controlled release feature of the drug-loaded composite coating. These findings suggested that the bilayer poly(lactic acid)/brushite coating provided effective protection for Mg alloy, greatly enhanced cytocompatibility and bioactivity, and, moreover, possessed local drug delivery capability; hence magnesium alloy with poly(lactic acid)/brushite coating presents great potential in orthopedic clinical applications, especially for localized bone therapy.

A strategy of suppressing the fast degradation behaviour of Mg-based biomaterials by the introduction of one of Mg degradation products Mg(OH)2 was proposed according to the following degradation mechanism, Mg + 2H2O ⇋ Mg(OH)2 + H2↑. Specifically, Mg(OH)2 submicron particles were mixed into poly (L-lactic acid) (PLLA) to synthesize a composite coating onto hydrofluoric acid-pretreated Mg-Nd-Zn-Zr alloy. The in vitro degradation investigations showed that the addition of Mg(OH)2 particles not only slowed down the corrosion of Mg matrix, but also retarded the formation of gas pockets underneath the polymer coating. Correspondingly, cytocompatibility results exhibited significant improvement of proliferation of endothelial cells, and further insights was gained into the mechanisms how the introduction of Mg(OH)2 particles into PLLA coating affected the magnesium alloy degradation and cytocompatibility. The present study provided a promising surface modification strategy to tailor the degradation behaviour of Mg-based biomaterials.