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.

A novel molecular classification method for osteosarcoma based on tumor cell differentiation trajectories

Subclassification of tumors based on molecular features may facilitate therapeutic choice and increase the response rate of cancer patients.However,the highly complex cell origin involved in osteosarcoma(OS)limits the utility of traditional bulk RNA sequencing for OS subclassification.Single-cell RNA sequencing(sc RNA-seq)holds great promise for identifying cell heterogeneity.However,this technique has rarely been used in the study of tumor subclassification.By analyzing sc RNA-seq data for six conventional OS and nine cancellous bone(CB)samples,we identified 29 clusters in OS and CB samples and discovered three differentiation trajectories from the cancer stem cell(CSC)-like subset,which allowed us to classify OS samples into three groups.The classification model was further examined using the TARGET dataset.Each subgroup of OS had different prognoses and possible drug sensitivities,and OS cells in the three differentiation branches showed distinct interactions with other clusters in the OS microenvironment.In addition,we verified the classification model through IHC staining in 138 OS samples,revealing a worse prognosis for Group B patients.Furthermore,we describe the novel transcriptional program of CSCs and highlight the activation of EZH2 in CSCs of OS.These findings provide a novel subclassification method based on sc RNA-seq and shed new light on the molecular features of CSCs in OS and may serve as valuable references for precision treatment for and therapeutic development in OS.

Visible Light-Induced 3D Bioprinting Technologies and Corresponding Bioink Materials for Tissue Engineering: A Review

Three-dimensional(3D)bioprinting based on traditional 3D printing is an emerging technology that is used to precisely assemble biocompatible materials and cells or bioactive factors into advanced tissue engineering solutions.Similar technology,particularly photo-cured bioprinting strategies,plays an important role in the field of tissue engineering research.The successful implementation of 3D bioprinting is based on the properties of photopolymerized materials.Photocrosslinkable hydrogel is an attractive biomaterial that is polymerized rapidly and enables process control in space and time.Photopolymerization is frequently initiated by ultraviolet(UV)or visible light.However,UV light may cause cell damage and thereby,affect cell viability.Thus,visible light is considered to be more biocompatible than UV light for bioprinting.In this review,we provide an overview of photo curing-based bioprinting technologies,and describe a visible light crosslinkable bioink,including its crosslinking mechanisms,types of visible light initiator,and biomedical applications.We also discuss existing challenges and prospects of visible light-induced 3D bioprinting devices and hydrogels in biomedical areas.

Nanoparticle–Cartilage Interaction: Pathology-Based Intra-articular Drug Delivery for Osteoarthritis Therapy

Osteoarthritis is the most prevalent chronic and debilitating joint disease,resulting in huge medical and socioeconomic burdens.Intra-articular administration of agents is clinically used for pain management.However,the effectiveness is inapparent caused by the rapid clearance of agents.To overcome this issue,nanoparticles as delivery systems hold considerable promise for local control of the pharmacokinetics of therapeutic agents.Given the therapeutic programs are inseparable from pathological progress of osteoarthritis,an ideal delivery system should allow the release of therapeutic agents upon specific features of disorders.In this review,we firstly introduce the pathological features of osteoarthritis and the design concept for accurate localization within cartilage for sustained drug release.Then,we review the interactions of nanoparticles with cartilage microenvironment and the rational design.Furthermore,we highlight advances in the therapeutic schemes according to the pathology signals.Finally,armed with an updated understanding of the pathological mechanisms,we place an emphasis on the development of“smart”bioresponsive and multiple modality nanoparticles on the near horizon to interact with the pathological signals.We anticipate that the exploration of nanoparticles by balancing the efficacy,safety,and complexity will lay down a solid foundation tangible for clinical translation.

Functionalized Hydrogels for Articular Cartilage Tissue Engineering

Articular cartilage(AC)is an avascular and flexible connective tissue located on the bone surface in the diarthrodial joints.AC defects are common in the knees of young and physically active individuals.Because of the lack of suitable tissue-engineered artificial matrices,current therapies for AC defects,espe-cially full-thickness AC defects and osteochondral interfaces,fail to replace or regenerate damaged carti-lage adequately.With rapid research and development advancements in AC tissue engineering(ACTE),functionalized hydrogels have emerged as promising cartilage matrix substitutes because of their favor-able biomechanical properties,water content,swelling ability,cytocompatibility,biodegradability,and lubricating behaviors.They can be rationally designed and conveniently tuned to simulate the extracel-lular matrix of cartilage.This article briefly introduces the composition,structure,and function of AC and its defects,followed by a comprehensive review of the exquisite(bio)design and(bio)fabrication of func-tionalized hydrogels for AC repair.Finally,we summarize the challenges encountered in functionalized hydrogel-based strategies for ACTE both in vivo and in vitro and the future directions for clinical translation.

Prevention of osteoporotic fracture:from skeletal and non-skeletal perspectives

With the global population aging,especially in China,the prevention and management of osteoporotic fragility fractures has become increasingly important.Bone mineral density(BMD)is an important index of osteoporotic fracture risk,which has become aroutine measurement inclinical practice and thus formed the cornerstone in monitoring treatment efficacy of osteoporosis.In the past 30 years,several pharmacologic therapies have been developed to increase BMD and reduce osteoporotic fractures,especially vertebral fractures.However,the management of nonvertebral fractures and hip fractures remains challenging as low BMD is only one of the multi-factors for these conditions.Hip fractures mainly result from a fall and its incidence is higher in the frigid zone due to low temperature affecting neuromuscular function and high latitude with less sunlight,the conditions rendering less active vitamin D conversion,apart from increased falling.In this paper,we focus on two therapeutic strategies targeting both skeletal and non-skeletal factors,that is,Tai Chi(TC)exercise for improving balance and"kidney-tonifying"traditional Chinese medicine(TCM)against muscle atrophy.TC is a mind-body exercise that has the potential as an effective and safe intervention for preventing fall-related fractures in the elderly.This makes it a promising and feasible physical activity for the elderly in frigid zone to prevent osteoporotic fractures.Several TCM formula popular in northeast of China within frigid zone are also introduced.They are reportedly effective in maintaining or improving BMD and muscle strength with the potential of reducing osteoporotic fracture.However,more rationally designed vigorous basic investigations and prospective clinical trials are highly desired to validate and consolidate the preliminary observations in the future.

Medical Additive Manufacturing: From a Frontier Technology to the Research and Development of Products

1.Research and development(R&D)and the challenges of raw materials for medical additive manufacturing Raw materials for medical additive manufacturing have a wide range of commonalities that are also seen in many other fields,making them an important basis in the field of three-dimensional(3D)printing.Problems and challenges related to material types,powder properties,formability,viscoelasticity,and so forth also share common features.For example,many metal materials are used in the field of aviation,while metals,polymers,and inorganic materials are used in the field of biomedicine.The most widely used materials in biomedicine are biocompatible.Various homogeneous and non-homogeneous composites are also available for 3D printing,and impose an additional challenge in additive manufacturing;the use of heterogeneous composites in 3D printing is particularly challenging.

Advanced Hydrogel systems for mandibular reconstruction

Mandibular defect becomes a prevalent maxillofacial disease resulting in mandibular dysfunctions and huge psychological burdens to the patients.Considering the routine presence of oral contaminations and aesthetic restoration of facial structures,the current clinical treatments are however limited,incapable to reconstruct the structural integrity and regeneration,spurring the need for cost-effective mandibular tissue engineering.Hydrogel systems possess great merit for mandibular reconstruction with precise involvement of cells and bioactive factors.In this review,current clinical treatments and distinct mode(s)of mandible formation and pathological resorption are summarized,followed by a review of hydrogel-related mandibular tissue engineering,and an update on the advanced fabrication of hydrogels with improved mechanical property,antibacterial ability,injectable form,and 3D bioprinted hydrogel constructs.The exploration of advanced hydrogel systems will lay down a solid foundation for a bright future with more biocompatible,effective,and personalized treatment in mandibular reconstruction.

Advancing drug delivery to articular cartilage:From single to multiple strategies

Articular cartilage(AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis(OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intraarticular drug delivery systems(DDSs) in the future.

O-alg-THAM/gel hydrogels functionalized with engineered microspheres based on mesenchymal stem cell secretion recruit endogenous stem cells for cartilage repair

Lacking self-repair abilities,injuries to articular cartilage can lead to cartilage degeneration and ultimately result in osteoarthritis.Tissue engineering based on functional bioactive scaffolds are emerging as promising approaches for articular cartilage regeneration and repair.Although the use of cell-laden scaffolds prior to implantation can regenerate and repair cartilage lesions to some extent,these approaches are still restricted by limited cell sources,excessive costs,risks of disease transmission and complex manufacturing practices.Acellular approaches through the recruitment of endogenous cells offer great promise for in situ articular cartilage regeneration.In this study,we propose an endogenous stem cell recruitment strategy for cartilage repair.Based on an injectable,adhesive and self-healable o-alg-THAM/gel hydrogel system as scaffolds and a biophysio-enhanced bioactive microspheres engineered based on hBMSCs secretion during chondrogenic differentiation as bioactive supplement,the as proposed functional material effectively and specifically recruit endogenous stem cells for cartilage repair,providing new insights into in situ articular cartilage regeneration.

Engineered biochemical cues of regenerative biomaterials to enhance endogenous stem/progenitor cells(ESPCs)-mediated articular cartilage repair

As a highly specialized shock-absorbing connective tissue,articular cartilage(AC)has very limited self-repair capacity after traumatic injuries,posing a heavy socioeconomic burden.Common clinical therapies for small-to medium-size focal AC defects are well-developed endogenous repair and cell-based strategies,including microfracture,mosaicplasty,autologous chondrocyte implantation(ACI),and matrix-induced ACI(MACI).However,these treatments frequently result in mechanically inferior fibrocartilage,low cost-effectiveness,donor site morbidity,and short-term durability.It prompts an urgent need for innovative approaches to pattern a pro-regenerative microenvironment and yield hyaline-like cartilage with similar biomechanical and biochemical properties as healthy native AC.Acellular regenerative biomaterials can create a favorable local environment for AC repair without causing relevant regulatory and scientific concerns from cell-based treatments.A deeper understanding of the mechanism of endogenous cartilage healing is furthering the(bio)design and application of these scaffolds.Currently,the utilization of regenerative biomaterials to magnify the repairing effect of joint-resident endogenous stem/progenitor cells(ESPCs)presents an evolving improvement for cartilage repair.This review starts by briefly summarizing the current understanding of endogenous AC repair and the vital roles of ESPCs and chemoattractants for cartilage regeneration.Then several intrinsic hurdles for regenerative biomaterials-based AC repair are discussed.The recent advances in novel(bio)design and application regarding regenerative biomaterials with favorable biochemical cues to provide an instructive extracellular microenvironment and to guide the ESPCs(e.g.adhesion,migration,proliferation,differentiation,matrix production,and remodeling)for cartilage repair are summarized.Finally,this review outlines the future directions of engineering the next-generation regenerative biomaterials toward ultimate clinical translation.

Anti-inflammatory and anabolic biphasic scaffold facilitates osteochondral tissue regeneration in osteoarthritic joints

Osteochondral defects (OCD) are common but difficult to heal due to the low intrinsic repair capacity of cartilage and its complex hierarchical structure. In osteoarthritis (OA), OCD become more challenging to repair as both cartilage and subchondral bone regeneration are further impaired due to the arthritic environment. Numerous biomaterials have been developed and tested in osteochondral defects while ignoring the inflammatory environment. To target this challenging underlying pathophysiology, we designed and fabricated a biphasic porous and degradable scaffold incorporating anti-inflammatory and anabolic molecules by low-temperature rapid prototyping technology, and its effects on promoting osteochondral regeneration were evaluated using our well-established OA-OCD rabbit model. The biphasic porous scaffolds consisted of poly lactic-co-glycolic acid (PLGA) with kartogenin (KGN) for cartilage repair and PLGA and β-calcium phosphate (PLGA/β-TCP) with cinnamaldehyde (CIN) for subchondral bone repair. KGN is a molecule for promoting chondrogenesis and CIN is a phytomolecule for enhancing osteogenesis and alleviating inflammation. The biphasic scaffolds PLGA/KGN-PLGA/β-TCP/CIN (PK/PTC) with bio-mimic structure provided stable mechanical properties and exhibited excellent biocompatibility to support cell adhesion, proliferation, migration, and distribution. Furthermore, KGN and CIN within biphasic scaffolds could be released in a controlled and sustained mode, and the biphasic scaffold degraded slowly in vitro . Evaluating the repair of 16-weeks post-implantation into critically sized OA-OCD rabbit models revealed that the biphasic scaffold could promote subchondral bone and cartilage regeneration, as well as reverse subchondral osteosclerosis caused by inflammation in vivo . These findings support the utilization of the PK/PTC scaffold for osteochondral regeneration and provide a promising potential strategy for clinical application for the treatment of patients with OA-OCD.

Materials evolution of bone plates for internal fixation of bone fractures:A review

Bone plates play a vital role in bone fracture healing by providing the necessary mechanical fixation for fracture fragments through modulating biomechanical microenvironment adjacent to the fracture site.Good treatment effect has been achieved for fixation of bone fracture with conventional bone plates,which are made of stainless steel or titanium alloy.However,several limitations still exist with traditional bone plates including loosening and stress shielding due to significant difference in modulus between metal material and bone tissue that impairs optimal fracture healing.Additionally,due to demographic changes and non-physiological loading,the population suffering from refractory fractures,such as osteoporosis fractures and comminuted fractures,is increasing,which imposes a big challenge to traditional bone plates developed for normal bone fracture repair.Therefore,optimal fracture treatment with adequate fixation implants in terms of materials and design relevant to special conditions is desirable.In this review,the complex physiological process of bone healing is introduced,followed by reviewing the development of implant design and biomaterials for bone plates.Finally,we discuss recent development of hybrid bone plates that contains bioactive elements or factors for fracture healing enhancement as a promising direction.This includes biodegradable Mg-based alloy used for designing bone screw-plates that has been proven to be beneficial for fracture healing,an innovative development that attracts more and more attention.This paper also indicates that the tantalum bone plates with porous structure are also emerging as a new fracture internal fixation implants.The reduction of the stress shielding is verified to be useful to accelerate bone fracture healing.Potential application of biodegradable metals may also avoid a second operation for implant removal.Further developments in biometals and their design for orthopedic bone plates are expected to improve the treatment of bone fracture,especially the refractory fractures.

Clinical translation and challenges of biodegradable magnesium-based interference screws in ACL reconstruction

As one of the most promising fixators developed for anterior cruciate ligament(ACL)reconstruction,biodegradable magnesium(Mg)-based interference screws have gained increasing attention attributed to their appropriate modulus and favorable biological properties during degradation after surgical insertion.However,its fast degradation and insufficient mechanical strength have also been recognized as one of the major causes to limit their further application clinically.This review focused on the following four parts.Firstly,the advantages of Mg or its alloys over their counterparts as orthopaedic implants in the fixation of tendon grafts in ACL reconstruction were discussed.Subsequently,the underlying mechanisms behind the contributions of Mg ions to the tendon-bone healing were introduced.Thirdly,the technical challenges of Mg-based interference screws towards clinical trials were discussed,which was followed by the introduction of currently used modification methods for gaining improved corrosion resistance and mechanical properties.Finally,novel strategies including development of Mg/Titanium(Ti)hybrid fixators and Mg-based screws with innovative structure for achieving clinically customized therapies were proposed.Collectively,the advancements in the basic and translational research on the Mg-based interference screws may lay the foundation for exploring a new era in the treatment of the tendon-bone insertion(TBI)and related disorders.

Synergistic effects of magnesium ions and simvastatin on attenuation of high-fat diet-induced bone loss

Introduction:Magnesium(Mg)has a prophylactic potential against the onset of hyperlipidemia.Similar to statin,Mg is recommended as lipid-lowering medication for hypercholesterolemia and concomitantly exhibits an association with increased bone mass.The combination of statin with Mg ions(Mg^(2+))may be able to alleviate the high-fat diet(HFD)-induced bone loss and reduce the side-effects of statin.This study aimed to explore the feasibility of combined Mg^(2+)with simvastatin(SIM)for treating HFD-induced bone loss in mice and the involving mechanisms.Materials and methods:C57BL/6 male mice were fed with a HFD or a normal-fat diet(NFD).Mice were intraperitoneally injected SIM and/or orally received water with additional Mg^(2+)until sacrificed.Enzyme-linked immunosorbent assay was performed to measure cytokines and cholesterol in serum and liver lysates.Bone mineral density(BMD)and microarchitecture were assessed by micro-computed tomography(μCT)in different groups.The adipogenesis in palmitate pre-treated HepG2 cells was performed under various treatments.Results:μCT analysis showed that the trabecular bone mass was significantly lower in the HFD-fed group than that in NFD-fed group since week 8.The cortical thickness in HFD-fed group had a significant decrease at week 24,as compared with NFD-fed group.The combination of Mg^(2+)and SIM significantly attenuated the trabecular bone loss in HFD-fed mice via arresting the osteoclast formation and bone resorption.Besides,such combination also reduced the hepatocytic synthesis of cholesterol and inhibited matrix metallopeptidase 13(Mmp13)mRNA expression in pre-osteoclasts.Conclusions:The combination of Mg^(2+)and SIM shows a synergistic effect on attenuating the HFD-induced bone loss.Our current formulation may be a cost-effective alternative treatment to be indicated for obesity-related bone loss.

Biodegradable magnesium pins enhanced the healing of transverse patellar fracture in rabbits

Displaced fractures of patella often require open reduction surgery and internal fixation to restore the extensor continuity and articular congruity.Fracture fixation with biodegradable magnesium(Mg)pins enhanced fracture healing.We hypothesized that fixation with Mg pins and their degradation over time would enhance healing of patellar fracture radiologically,mechanically,and histologically.Transverse patellar fracture surgery was performed on thirty-two 18-weeks old female New Zealand White Rabbits.The fracture was fixed with a pin made of stainless steel or pure Mg,and a figure-of-eight stainless steel band wire.Samples were harvested at week 8 or 12,and assessed with microCT,tensile testing,microindentation,and histology.Microarchitectural analysis showed that Mg group showed 12%higher in the ratio of bone volume to tissue volume at week 8,and 38.4%higher of bone volume at week 12.Tensile testing showed that the failure load and stiffness of Mg group were 66.9%and 104%higher than the control group at week 8,respectively.At week 12,Mg group was 60.8%higher in ultimate strength than the control group.Microindentation showed that,compared to the Control group,Mg group showed 49.9%higher Vickers hardness and 31%higher elastic modulus at week 8 and 12,respectively.At week 12,the new bone of Mg group remodelled to laminar bone,but those of the control group remained woven bone-like.Fixation of transverse patellar fracture with Mg pins and its degradation enhanced new bone formation and mechanical properties of the repaired patella compared to the Control group.

An overview of graphene-based hydroxyapatite composites for orthopedic applications

Hydroxyapatite(HA)is an attractive bioceramic for hard tissue repair and regeneration due to its physicochemical similarities to natural apatite.However,its low fracture toughness,poor tensile strength and weak wear resistance become major obstacles for potential clinical applications.One promising method to tackle with these problems is exploiting graphene and its derivatives(graphene oxide and reduced graphene oxide)as nanoscale reinforcement fillers to fabricate graphene-based hydroxyapatite composites in the form of powders,coatings and scaffolds.The last few years witnessed increasing numbers of studies on the preparation,mechanical and biological evaluations of these novel materials.Herein,various preparation techniques,mechanical behaviors and toughen mechanism,the in vitro/in vivo biocompatible analysis,antibacterial properties of the graphene-based HA composites are presented in this review.

3D-printed NIR-responsive shape memory polyurethane/magnesium scaffolds with tight-contact for robust bone regeneration

Patients with bone defects suffer from a high rate of disability and deformity.Poor contact of grafts with defective bones and insufficient osteogenic activities lead to increased loose risks and unsatisfied repair efficacy.Although self-expanding scaffolds were developed to enhance bone integration,the limitations on the high transition temperature and the unsatisfied bioactivity hindered greatly their clinical application.Herein,we report a near-infrared-responsive and tight-contacting scaffold that comprises of shape memory polyurethane(SMPU)as the thermal-responsive matrix and magnesium(Mg)as the photothermal and bioactive component,which fabricated by the low temperature rapid prototyping(LT-RP)3D printing technology.As designed,due to synergistic effects of the components and the fabrication approach,the composite scaffold possesses a homogeneously porous structure,significantly improved mechanical properties and stable photothermal effects.The programmed scaffold can be heated to recover under near infrared irradiation in 60s.With 4 wt%Mg,the scaffold has the balanced shape fixity ratio of 93.6%and shape recovery ratio of 95.4%.The compressed composite scaffold could lift a 100 g weight under NIR light,which was more than 1700 times of its own weight.The results of the push-out tests and the finite element analysis(FEA)confirmed the tight-contacting ability of the SMPU/4 wt%Mg scaffold,which had a signficant enhancement compared to the scaffold without shape memory effects.Furthermore,The osteopromotive function of the scaffold has been demonstrated through a series of in vitro and in vivo studies.We envision this scaffold can be a clinically effective strategy for robust bone regeneration.

Corrosion and biocompatibility improvement of magnesium-based alloys as bone implant materials:a review

Magnesium(Mg)or its alloys are widely tested as potential orthopedic implants,particularly as biodegradable alloys for fracture fixation due to their mechanical properties are close to those of bone.Currently,available Mg or its alloys are confronted with challenges in passing regulatory biosafety tests prior to clinical trials due to its fast degradation and associated degradation products.The degradation of Mg is accompanied by the release of Mg ions,the rise of pH and osmolality in surrounding environments.According to the standard of ISO 10993 Part 13,the pH value shall be appropriate to the site of intended use maintaining in an appropriate range.Approaches to overcome these challenges include the selection of adequate alloying elements,proper surface treatment techniques and control of the degradation rate of Mg or its alloys developed as orthopedic implants.To date,Mg or its alloy-based bone implants have not yet been widely used in clinical applications as medical implants.This review critically summarized published methods to improve the corrosion resistance of Mg and its alloys.The current progress on in vitro cytotoxicity and in vivo biocompatibility properties of these metals was also reviewed.This review aimed to provide a reference for further research and development(R&D)of biodegradable Mg and its alloys with regard to the evaluation of their corrosion process and biocompatibility and facilitation of their translation to clinical applications.

Combination of magnesium ions and vitamin C alleviates synovitis and osteophyte formation in osteoarthritis of mice

Introduction:We previously demonstrated that magnesium ions(Mg^(2+))was a novel therapeutic alternative for osteoarthritis(OA)through promoting the hypoxia inducible factor-1α(HIF-1α)-mediated cartilage matrix synthesis.However,oxidative stress can inhibit the expression of HIF-1α,amplify the inflammation that potentially impairs the therapeutic efficacy of Mg^(2+) in OA.Vitamin(VC),a potent antioxidant,may enhance the efficacy of Mg^(2+) in OA treatment.This study aims to investigate the efficacy of combination of Mg^(2+)and VC on alleviating joint destruction and pain in OA.Material and methods:Anterior cruciate ligament transection with partial medial meniscectomy induced mice OA model were randomly received intra-articular injection of either saline,MgCl2(0.5 mol/L),VC(3 mg/ml)or MgCl2(0.5 mol/L)plus VC(3 mg/ml)at week 2 post-operation,twice weekly,for 2 weeks.Joint pain and pathological changes were assessed by gait analysis,histology,western blotting and micro-CT.Results:Mg^(2+) and VC showed additive effects to significantly alleviate the joint destruction and pain.The efficacy of this combined therapy could sustain for 3 months after the last injection.We demonstrated that VC enhanced the promotive effect of Mg^(2+) on HIF-1αexpression in cartilage.Additionally,combination of Mg^(2+) and VC markedly promoted the M2 polarization of macrophages in synovium.Furthermore,combination of Mg^(2+) and VC inhibited osteophyte formation and expressions of pain-related neuropeptides.Conclusions:Intra-articular administration of Mg^(2+)and VC additively alleviates joint destruction and pain in OA.Our current formulation may be a cost-effective alternative treatment for OA.