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.

Update on the research and development of magnesium-based biodegradable implants and their clinical translation in orthopaedics

Biodegradable magnesium(Mg)or its alloys are desirable materials for development into new-generation internal fixation devices or implants with high biocompatibility,adequate mechanical modulus,and osteopromotive properties,which may overcome some of the drawbacks of the existing permanent orthopaedic implants with regard to stress-shielding of bone and beam-hardening effects on radiographic images.This review summarises the current research status of Mg-based orthopaedic implants in animals and clinical trials.First,detailed information of animal studies including bone fracture repair and anterior cruciate ligament reconstruction with the use of Mg-based orthopaedic devices is introduced.Second,the repair mechanisms of the Mg-based orthopaedic implants are also reviewed.Afterwards,reports of recent clinical cases treated using Mg-based implants in orthopaedics are summarised.Finally,the challenges and the strategies of the use of Mg-based orthopaedic implants are discussed.Taken together,the collected efforts in basic research,translational work,and clinical applications of Mg-based orthopaedic implants over the last decades greatly contribute to the development of a new generation of biodegradable metals used for the design of innovative implants for better treatment of orthopaedic conditions in patients with challenging skeletal disorders or injuries.

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.

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.

Anti-infection mechanism of a novel dental implant made of titanium-copper(TiCu)alloy and its mechanism associated with oral microbiology

This work was focused on study of anti-infection ability and its underlying mechanism of a novel dental implant made of titanium-copper(TiCu)alloy.In general,most studies on antibacterial implants have used a single pathogen to test their anti-infection ability using infectious animal models.However,dental implant-associated infections are polymicrobial diseases.We innovatively combine the classic ligature model in dogs with sucrose-rich diets to induce oral infections via the canine native oral bacteria.The anti-infection ability,biocompatibility and underlying mechanism of TiCu implant were systematically investigated in comparison with pure Ti implant via general inspection,hematology,imageology(micro-CT),microbiology(16S rDNA and metagenome),histology,and Cu ion detections.Compared with Ti implant,TiCu implant demonstrated remarkable anti-infection potentials with excellent biocompatibility.Additionally,the underlying anti-infection mechanism of TiCu implant was considered to involve maintaining the oral microbiota homeostasis.It was found that the carbohydrates in the plaques formed on the surface of TiCu implant were metabolized through the tricarboxylic acid cycle(TCA)cycles,which prevented the formation of an acidic microenvironment and inhibited the accumulation of acidogens and pathogens,thereby maintaining the microflora balance between aerobic and anaerobic bacteria.