Incorporation of Mg-phenolic networks as a protective coating for magnesium alloy to enhance corrosion resistance and osteogenesis in vivo

Magnesium(Mg) and its alloys have been intensively studied to develop the next generation of bone implants recently, but their clinical application is restricted by rapid degradation and unsatisfied osteogenic effect in vivo. A bioactive chemical conversion Mg-phenolic networks complex coating(e EGCG) was stepwise incorporated by epigallocatechin-3-gallate(EGCG) and exogenous Mg^(2+)on Mg-2Zn magnesium alloy. Simplex EGCG induced chemical conversion coating(c EGCG) was set as compare group. The in vitro corrosion behavior of Mg-2Zn alloy, c EGCG and e EGCG was evaluated in SBF using electrochemical(PDP, EIS) and immersion test. The cytocompatibility was investigated with rat bone marrow mesenchymal stem cells(r BMSCs). Furthermore, the in vivo tests using a rabbit model involved micro computed tomography(Micro-CT) analysis, histological observation, and interface analysis. The results showed that the e EGCG is Mgphenolic multilayer coating incorporated Mg-phenolic networks, which is rougher, more compact and much thicker than c EGCG. The e EGCG highly improved the corrosion resistance of Mg-2Zn alloy, combined with its lower average hemolytic ratios, continuous high scavenging effect ability and relatively moderate contact angle features, resulting in a stable and suitable biological environment, obviously promoted r BMSCs adhesion and proliferation. More importantly, Micro-CT, histological and interface elements distribution evaluations all revealed that the e EGCG effectively inhibited degradation and enhanced bone tissue formation of Mg alloy implants. This study puts forward a promising bioactive chemical conversion coating with Mg-phenolic networks for the application of biodegradable orthopedic implants.

An extracellular matrix-mimetic coating with dual bionics for cardiovascular stents

Anti-inflammation and anti-coagulation are the primary requirements for cardiovascular stents and also the widely accepted trajectory for multi-functional modification.In this work,we proposed an extracellular matrix(ECM)-mimetic coating for cardiovascular stents with the amplified functionalization of recombinant humanized collagen type III(rhCOL III),where the biomimetics were driven by structure mimicry and component/function mimicry.Briefly,the structure-mimic was constructed by the formation of a nanofiber(NF)structure via the polymerization of polysiloxane with a further introduction of amine groups as the nanofibrous layer.The fiber network could function as a three-dimensional reservoir to support the amplified immobilization of rhCoL III.The rhCOL III was tailored for anti-coagulant,anti-inflammatory and endothelialization promotion properties,which endows the ECM-mimetic coating with desired surface functionalities.Stent implantation in the abdominal aorta of rabbits was conducted to validate the in vivo re-endothelialization of the ECM-mimetic coating.The mild inflammatory responses,anti-thrombotic property,promotion of endothelialization and suppression of excessive neointimal hyperplasia confirmed that the ECM-mimetic coating provided a promising approach for the modification of vascular implants.

Platelet Membrane-Coated Nanocarriers Targeting Plaques to Deliver Anti-CD47 Antibody for Atherosclerotic Therapy

Atherosclerosis,the principle cause of cardiovascular disease(CVD)worldwide,is mainly characterized by the pathological accumulation of diseased vascular cells and apoptotic cellular debris.Atherogenesis is associated with the upregulation of CD47,a key antiphagocytic molecule that is known to render malignant cells resistant to programmed cell removal,or“efferocytosis.”Here,we have developed platelet membrane-coated mesoporous silicon nanoparticles(PMSN)as a drug delivery system to target atherosclerotic plaques with the delivery of an anti-CD47 antibody.Briefly,the cell membrane coat prolonged the circulation of the particles by evading the immune recognition and provided an afinity to plaques and atherosclerotic sites.The anti-CD47 antibody then normalized the clearance of diseased vascular tissue and further ameliorated atherosclerosis by blocking CD47.In an atherosclerosis model established in ApoE^(-/-)mice,PMSN encapsulating anti-CD47 antibody delivery significantly promoted the efferocytosis of necrotic cells in plaques.Clearing the necrotic cells greatly reduced the atherosclerotic plaque area and stabilized the plaques reducing the risk of plaque rupture and advanced thrombosis.Overall,this study demonstrated the therapeutic advantages of PMSN encapsulating anti-CD47 antibodies for atherosclerosis therapy,which holds considerable promise as a new targeted drug delivery platform for efficient therapy of atherosclerosis。

The biological responses and mechanisms of endothelial cells to magnesium alloy

Due to its good biocompatibility and degradability,magnesium alloy(Mg alloy)has shown great promise in cardiovascular stent applications.Rapid stent re-endothelialization is derived from migrated and adhered endothelial cells(ECs),which is an effective way to reduce late thrombosis and inhibit hyperplasia.However,fundamental questions regarding Mg alloy affecting migration and adhesion of ECs are not fully understood.Here,we evaluated the effects of Mg alloy on the ECs proliferation,adhesion and migration.A global gene expression profiling of ECs co-culturing with Mg alloy was conducted,and the adhesion-and migration-related genes were examined.We found that Mg alloy had no adverse effects on ECs viability but significantly affected ECs migration and adhesion.Co-cultured with Mg alloy extract,ECs showed contractive adhesion morphology and decreased motility,which was supported by the down-regulation of adhesion-related genes(Paxillin and Vinculin)and migration-related genes(RAC 1,Rho A and CDC 42).Accordingly,the re-endothelialization of Mg alloy stent was inhibited in vivo.Our results may provide new inspiration for improving the broad application of Mg alloy stents.

Electrospun silk fibroin/poly(L-lactide-ecaplacton)graft with platelet-rich growth factor for inducing smooth muscle cell growth and infiltration

The construction of a smooth muscle layer for blood vessel through electrospinning method plays a key role in vascular tissue engineering.However,smooth muscle cells(SMCs)penetration into the electrospun graft to form a smooth muscle layer is limited due to the dense packing of fibers and lack of inducing factors.In this paper,silk fibroin/poly(L-lactide-e-caplacton)(SF/PLLA-CL)vascular graft loaded with platelet-rich growth factor(PRGF)was fabricated by electrospinning.The in vitro results showed that SMCs cultured in the graft grew fast,and the incorporation of PRGF could induce deeper SMCs infiltrating compared to the SF/PLLA-CL graft alone.Mechanical properties measurement showed that PRGF-incorporated graft had proper tensile stress,suture retention strength,burst pressure and compliance which could match the demand of native blood vessel.The success in the fabrication of PRGF-incorporated SF/PLLA-CL graft to induce fast SMCs growth and their strong penetration into graft has important application for tissue-engineered blood vessels.

Yes-associated protein contributes to magnesium alloy-derivedinflammation in endothelial cells

Magnesium alloy(Mg alloy)has attracted massive attention in the potential applications of cardiovascular stents because of its good biocompatibility and degradability.However,whether and how the Mg alloy induces inflammation in endothelial cells remains unclear.In the present work,we investigated the activation of Yes-associated protein(YAP)upon Mg alloy stimuli and unveiled the transcriptional function in Mg alloy-induced inflammation.Quantitative RT–PCR,western blotting and immunofluorescence staining showed that Mg alloy inhibited the Hippo pathway to facilitate nuclear shuttling and activation of YAP in human coronary artery endothelial cells(HCAECs).Chromatin immunoprecipitation followed sequencing was carried out to explore the transcriptional function of YAP in Mg alloy-derived inflammation.This led to the observation that nuclear YAP further bonded to the promoter region of inflammation transcription factors and co-transcription factors.This binding event activated their transcription and modified mRNA methylation of inflammation-related genes through regulating the expression of N6-methyladenosine modulators(METTL3,METTL14,FTO and WTAP).This then promoted inflammation-related gene expression and aggravated inflammation in HCAECs.In YAP deficiency cells,Mg alloy-induced inflammation was reduced.Collectively,our data suggest that YAP contributes to the Mg alloy-derived inflammation in HCAECs and may provide a potential therapeutic target that alleviates inflammation after Mg alloy stent implantation.

Multifunctional mussel-inspired copolymerized epigallocatechin gallate(EGCG)/arginine coating:the potential as an ad-layer for vascular materials

Surface properties are considered to be important factors in addressing proper functionalities.In this paper,a multifunctional mussel-inspired coating was prepared via the direct copolymerization of epigallocatechin gallate(EGCG)and arginine.The coating formation was confirmed by X-ray photoelectron spectroscopy and Fourier transform infrared spectra.The EGCG/arginine coating contained diverse functional groups like amines,phenols and carboxyls,whose densities were also tunable.Such mussel-inspired coating could also be applied as an ad-layer for its secondary reactivity,demonstrated by quartz crystal microbalance technique.Moreover,the tunable surface density of phenols showed potential ability in modulating endothelial cell and smooth muscle cell viability.The coatings rich in phenols presented excellent free radical scavenging property.Current results strongly indicated the potential of EGCG/arginine coatings to be applied as an ad-layer for vascular materials.

Stability research on polydopamine and immobilized albumin on 316L stainless steel

In this study,the polydopamine(PDA)film was coated on polished 316Lss and then thermally treated at 150C(labeled as PDA-Th150),and the stability of coatings was also investigated.Straining test indicated that PDA-Th150 coating performed better in affording sufficient adherence to 316 L SS substrate.Moreover,both PDA and PDA-Th150 coating suffered slight swelling during immersion in deionized water(pH紏6.5).X-ray photoelectron spectroscopy results showed that during immersion,latent nucleophilic reaction via amines inside PDA coating occurred.This led to an enhanced cross-linking and thus gradually promoted the coating stability.Moreover,larger amount of bovine serum albumin(BSA)was immobilized onto PDA-Th150 coating and performed well in anti-platelet adhesion.A high retention of immobilized BSA was observed even after immersion for 30 days.These tests suggested that PDA was stable enough and performed well in surface functionalization,which might enrich the research and application of PDA.