High formability Mg-Zn-Gd wire facilitates ACL reconstruction via its swift degradation to accelerate intra-tunnel endochondral ossification

After reconstructing the anterior cruciate ligament(ACL),unsatisfactory bone tendon interface healing may often induce tunnel enlargement at the early healing stage.With good biological features and high formability,Magnesium-Zinc-Gadolinium(ZG21)wires are developed to bunch the tendon graft for matching the bone tunnel during transplantation.Microstructure,tensile strength,degradation,and cytotoxicity of ZG21 wire are evaluated.The rabbit model is used for assessing the biological effects of ZG21 wire by Micro-CT,histology,and mechanical test.The SEM/EDS,immunochemistry,and in vitro assessments are performed to investigate the underlying mechanism.Material tests demonstrate the high formability of ZG21 wire as surgical suture.Micro-CT shows ZG21 wire degradation accelerates tunnel bone formation,and histologically with earlier and more fibrocartilage regeneration at the healing interface.The mechanical test shows higher ultimate load in the ZG21 group.The SEM/EDS presents ZG21 wire degradation triggered calcium phosphate(Ca-P)deposition.IHC results demonstrate upregulation of Wnt3a,BMP2,and VEGF at the early phase and TGFβ3 and Type II collagen at the late phase of healing.In vitro tests also confirmed the Ca-P in the metal extract could elevate the expression of Wnt3a,βcatenin,ocn and opn to stimulate osteogenesis.Ex vivo tests of clinical samples indicated suturing with ZG21 wire did not weaken the ultimate loading of human tendon tissue.In conclusion,the ZG21 wire is feasible for tendon graft bunching.Its degradation products accelerated intra-tunnel endochondral ossification at the early healing stage and therefore enhanced bone-tendon interface healing in ACL reconstruction.

Challenges and Solutions for the Additive Manufacturing of H) Biodegradable Magnesium Implants

Due to their capability of fabricating geometrically complex structures,additive manufacturing(AM)techniques have provided unprecedented opportunities to produce biodegradable metallic implants—especially using Mg alloys,which exhibit appropriate mechanical properties and outstanding biocompatibility.However,many challenges hinder the fabrication of AM-processed biodegradable Mg-based implants,such as the difficulty of Mg powder preparation,powder splash,and crack formation during the AM process.In the present work,the challenges of AM-processed Mg components are analyzed and solutions to these challenges are proposed.A novel Mg-based alloy(Mg-Nd-Zn-Zr alloy,JDBM)powder with a smooth surface and good roundness was first synthesized successfully,and the AM parameters for Mg-based alloys were optimized.Based on the optimized parameters,porous JDBM scaffolds with three different architectures(biomimetic,diamond,and gyroid)were then fabricated by selective laser melting(SLM),and their mechanical properties and degradation behavior were evaluated.Finally,the gyroid scaffolds with the best performance were selected for dicalcium phosphate dihydrate(DCPD)coating treatment,which greatly suppressed the degradation rate and increased the cytocompatibility,indicating a promising prospect for clinical application as bone tissue engineering scaffolds.

In vitro and in vivo evaluations of Mg-Zn-Gd alloy membrane on guided bone regeneration for rabbit calvarial defect

To develop a biodegradable membrane with guided bone regeneration(GBR),a Mg-2.0Zn-1.0Gd alloy(wt.%,MZG)membrane with Ca-P coating was designed and fabricated in this study.The microstructure,hydrophilicity,in vitro degradation,cytotoxicity,antibacterial effect and in vivo regenerative performance for the membrane with and without Ca-P coating were evaluated.After coating,the membrane exhibited an enhance hydrophilicity and corrosion resistance,showed good in vitro cytocompatibility upon MC3T3E-1 cells,and exhibited excellent antibacterial effect against E.coli,Staphylococcus epidermis and Staphylococcus aureus,simultaneously.In vivo experiment using the rabbit calvarial defect model confirmed that Ca-P coated MZG membrane underwent progressive degradation without inflammatory reaction and significantly improved the new bone formation at both 1.5 and 3 months after the surgery.All the results strongly indicate that MZG with Ca-P coating have great potential for clinical application as GBR membranes.

Exploring the interconnectivity of biomimetic hierarchical porous Mg scaffolds for bone tissue engineering:Effects of pore size distribution on mechanical properties,degradation behavior and cell migration ability

Interconnectivity is the key characteristic of bone tissue engineering scaffold modulating cell migration,blood vessels invasion and transport of nutrient and waste.However,efforts and understanding of the interconnectivity of porous Mg is limited due to the diverse architectures of pore struts and pore size distribution of Mg scaffold systems.In this work,biomimetic hierarchical porous Mg scaffolds with tailored interconnectivity as well as pore size distribution were prepared by template replication of infiltration casting.Mg scaffold with better interconnectivity showed lower mechanical strength.Enlarging interconnected pores would enhance the interconnectivity of the whole scaffold and reduce the change of ion concentration,pH value and osmolality of the degradation microenvironment due to the lower specific surface area.Nevertheless,the degradation rates of five tested Mg scaffolds were no different because of the same geometry of strut unit.Direct cell culture and evaluation of cell density at both sides of four typical Mg scaffolds indicated that cell migration through hierarchical porous Mg scaffolds could be enhanced by not only bigger interconnected pore size but also larger main pore size.In summary,design of interconnectivity in terms of pore size distribution could regulate mechanical strength,microenvironment in cell culture condition and cell migration potential,and beyond that it shows great potential for personalized therapy which could facilitate the regeneration process.

Fabrication of ultra-high strength magnesium alloys over 540 MPa with low alloying concentration by double continuously extrusion

We prepare a new type of patented biodegradable biomedical Mg-Nd-Zn-Zr(JDBM)alloy system and impose double continuously extrusion(DCE)processing.The lowest processing temperature is 250℃for JDBM-2.1Nd and 310℃for JDBM-2.8Nd,which increases with the Nd concentration.The highest yield strength of 541 MPa is achieved in JDBM-2.1 Nd samples when extruded at 250℃and the elongation is about 3.7%.Moreover,the alloy with a lower alloying element content can reach a higher yield strength while that with a higher alloying element content can reach a larger elongation after DCE processing.However,when extruded under the same conditions,the alloy with a higher alloying contents exhibits better tensile properties.

Effects of dynamic flow rates on degradation deposition behavior of Mg scaffold

Degradability of bone tissue engineering scaffold that matching the regeneration rate could allow a complete replacement of host tissue.However,the porous structure of biodegradable Mg scaffolds certainly generated high specific surface area,and the three-dimensional interconnected pores provided fast pervasive invasion entrance for the corrosive medium,rising concern of the structural integrity during the degradation.To clarify the structural evolution of the three-dimensional(3D)porous structure,semi-static immersion tests were carried out to evaluate the degradation performance in our previous study.Nevertheless,dynamic immersion tests mimicking the in vivo circulatory fluid through the interconnected porous structure have yet been investigated.Moreover,the effects of dynamic flow rates on the degradation deposition behavior of 3D porous Mg scaffolds were rarely reported.In this study,Mg scaffolds degraded at three flow rates exhibited different degradation rates and deposition process.A flow rate of 0.5 m L/min introduced maximum drop of porosity by accumulated deposition products.The deposition products provided limited protection against the degradation process at a flow rate of 1.0 m L/min.The three-dimensional interconnected porous structure of Mg scaffold degraded at 2.0 m L/min well retained after 14 days showing the best interconnectivity resistance to the degradation deposition process.The dynamic immersion tests disclosed the reason for the different degradation rates on account of flow rates,which may bring insight into understanding of varied in vivo degradation rates related to implantation sites.

Concerting magnesium implant degradation facilitates local chemotherapy in tumor-associated bone defect

Effective management of malignant tumor-induced bone defects remains challenging due to severe systemic side effects,substantial tumor recurrence,and long-lasting bone reconstruction post tumor resection.Magnesium and its alloys have recently emerged in clinics as orthopedics implantable metals but mostly restricted to mechanical devices.Here,by deposition of calcium-based bilayer coating on the surface,a Mg-based composite implant platform is developed with tailored degradation characteristics,simultaneously integrated with chemotherapeutic(Taxol)loading capacity.The delicate modulation of Mg degradation occurring in aqueous environment is observed to play dual roles,not only in eliciting desirable osteoinductivity,but allows for modification of tumor microenvironment(TME)owing to the continuous release of degradation products.Specifically,the sustainable H2 evolution and Ca2+from the implant is distinguished to cooperate with local Taxol delivery to achieve superior antineoplastic activity through activating Cyt-c pathway to induce mitochondrial dysfunction,which in turn leads to significant tumor-growth inhibition in vivo.In addition,the local chemotherapeutic delivery of the implant minimizes toxicity and side effects,but markedly fosters osteogenesis and bone repair with appropriate structure degradation in rat femoral defect model.Taken together,a promising intraosseous administration strategy with biodegradable Mg-based implants to facilitate tumor-associated bone defect is proposed.

Challenges and strategies for in situ endothelialization and long-term lumen patency of vascular grafts

Vascular diseases are the most prevalent cause of ischemic necrosis of tissue and organ,which even result in dysfunction and death.Vascular regeneration or artificial vascular graft,as the conventional treatment modality,has received keen attentions.However,small-diameter(diameter<4 mm)vascular grafts have a high risk of thrombosis and intimal hyperplasia(IH),which makes long-term lumen patency challengeable.Endothelial cells(ECs)form the inner endothelium layer,and are crucial for anti-coagulation and thrombogenesis.Thus,promoting in situ endothelialization in vascular graft remodeling takes top priority,which requires recruitment of endothelia progenitor cells(EPCs),migration,adhesion,proliferation and activation of EPCs and ECs.Chemotaxis aimed at ligands on EPC surface can be utilized for EPC homing,while nanofibrous structure,biocompatible surface and cell-capturing molecules on graft surface can be applied for cell adhesion.Moreover,cell orientation can be regulated by topography of scaffold,and cell bioactivity can be modulated by growth factors and therapeutic genes.Additionally,surface modification can also reduce thrombogenesis,and some drug release can inhibit IH.Considering the influence of macrophages on ECs and smooth muscle cells(SMCs),scaffolds loaded with drugs that can promote M2 polarization are alternative strategies.In conclusion,the advanced strategies for enhanced long-term lumen patency of vascular grafts are summarized in this review.Strategies for recruitment of EPCs,adhesion,proliferation and activation of EPCs and ECs,anti-thrombogenesis,anti-IH,and immunomodulation are discussed.Ideal vascular grafts with appropriate surface modification,loading and fabrication strategies are required in further studies.

Nano-micrometer surface roughness gradients reveal topographical influences on differentiating responses of vascular cells on biodegradable magnesium

Distinctively directing endothelial cells(ECs)and smooth muscle cells(SMCs),potentially by surface topography cue,is of central importance for enhancing bioefficacy of vascular implants.For the first time,surface gradients with a broad range of nano-micrometer roughness are developed on Mg,a promising next-generation biodegradable metal,to carry out a systematic study on the response of ECs and SMCs.Cell adhesion,spreading,and proliferation are quantified along gradients by high-throughput imaging,illustrating drastic divergence between ECs and SMCs,especially in highly rough regions.The profound role of surface topography overcoming the biochemical cue of released Mg2+is unraveled at different roughness ranges for ECs and SMCs.Further insights into the underlying regulatory mechanism are gained at subcellular and gene levels.Our work enables highefficient exploration of optimized surface morphology for modulating favored cell selectivity of promoting ECs and suppressing SMCs,providing a potential strategy to achieve rapid endothelialization for Mg.

Effect of grain size on the mechanical properties of Mg foams

The grain size of Mg foams was innovatively refined without alteration of pore structure and relative density by subjecting multi-axial forging(MAF)process to Ti-Mg composite,an intermediary product of the fabrication process of Mg foams where the spherical Ti particles were utilized as the replication material.The feasibility of the MAF process and the grain size effect on the mechanical properties of Mg foams were discussed.The results showed that,with the appropriate strain of 0.24 applied in the MAF process,Ti-Mg composites returned to original physical appearance without generating microcracks.And complete recrystallization was achieved after heat treatment,with the grain size of the MAFprocessed Mg foams two to three orders of magnitude smaller than that of as-cast foam.The mechanical properties of Mg foams were enhanced extensively after grain refinement with the yield strength and the plastic collapse strength increased by 147%and 50.7%,respectively.A revised model integrated by the Hall-Petch law and Gibson-Ashby model was proposed,which gave a good estimation of the yield strength and the plastic collapse strength of Mg foams from the compressive behavior of the corresponding parent material,though a knockdown factor of 0.45 was introduced for the yield strength.

Research and development strategy for biodegradable magnesium-based vascular stents:a review

Magnesium alloys are an ideal material for biodegradable vascular stents,which can be completely absorbed in the human body,and have good biosafety and mechanical properties.However,the rapid corrosion rate and excessive localized corrosion,as well as challenges in the preparation and processing of microtubes for stents,are restricting the clinical application of magnesium-based vascular stents.In the present work we will give an overview of the recent progresses on biodegradable magnesium based vascular stents including magnesium alloy design,high-precision microtubes processing,stent shape optimisation and functional coating preparation.In particular,the Triune Principle in biodegradable magnesium alloy design is proposed based on our research experience,which requires three key aspects to be considered when designing new biodegradable magnesium alloys for vascular stents application,i.e.biocompatibility and biosafety,mechanical properties,and biodegradation.This review hopes to inspire the future studies on the design and development of biodegradable magnesium alloy-based vascular stents.

Mechanical and corrosion properties of biodegradable magnesium mini-tubes with different grain morphologies:Size and distribution

Biodegradable magnesium(Mg)alloys have received much attention due to their biocompatibility and biodegradation.In this study,to uncover the effects of grain morphologies,including grain size and distribution on mechanical and corrosion properties,biodegradable Mg-2.1Nd-0.2Zn-0.5Zr(wt.%)(denoted as JDBM)alloy mini-tubes for stent application with three typical microstructures were achieved success-fully by adjusting drawing parameters.Samples with the bimodal structure exhibit the highest strengthductility balance attributed to the combined effects of fine grains and coarse grains,but show the fastest corrosion rate of about 1.00±0.136 mm/year mainly due to the formation of micro galvanic couples between coarse and fined grains.Samples with fine equiaxed grains show the lowest corrosion rate of about 0.17±0.059 mm/year,as well as uniform corrosion mode and mechanical properties of yield strength(YS)256±5.7 MPa,ultimate tensile strength(UTS)266±3.8 MPa,and elongation to failure(EL)13.5%±1.8%,attributed to the high-density grain boundaries.Samples with coarse equiaxed grains exhibit medium corrosion resistance and mechanical properties of about 175±4.8 MPa,221±4.0 MPa,and 21.53%±4.1%.Considering the mechanical and in vitro corrosion properties,biodegradable JDBM alloy implants are recommended to be composed of fine equiaxed grains,which can be used as microstructural targets for fabrication and processing.