Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pa...Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.展开更多
The death of osteoblasts induced by glucocorticoid(GC)-mediated oxidative stress plays a crucial role in the development of steroid-induced osteonecrosis of the femoral head(SIONFH).Improving bone formation driven by ...The death of osteoblasts induced by glucocorticoid(GC)-mediated oxidative stress plays a crucial role in the development of steroid-induced osteonecrosis of the femoral head(SIONFH).Improving bone formation driven by osteoblasts has shown promising outcomes in the prognosis of SIONFH.Isovitexin has demonstrated antioxidant properties,but its therapeutic effects on GC-induced oxidative stress and SIONFH remain unexplored.In this study,we analyzed clinical samples obtained from SIONFH patients using proteomic and bioinformatic approaches.展开更多
The skeleton is innervated by different types of nerves and receives signaling from the nervous system to maintain homeostasis and facilitate regeneration or repair.Although the role of peripheral nerves and signals i...The skeleton is innervated by different types of nerves and receives signaling from the nervous system to maintain homeostasis and facilitate regeneration or repair.Although the role of peripheral nerves and signals in regulating bone homeostasis has been extensively investigated,the intimate relationship between the central nervous system and bone remains less understood,yet it has emerged as a hot topic in the bone field.In this review,we discussed clinical observations and animal studies that elucidate the connection between the nervous system and bone metabolism,either intact or after injury.First,we explored mechanistic studies linking specific brain nuclei with bone homeostasis,including the ventromedial hypothalamus,arcuate nucleus,paraventricular hypothalamic nucleus,amygdala,and locus coeruleus.We then focused on the characteristics of bone innervation and nerve subtypes,such as sensory,sympathetic,and parasympathetic nerves.Moreover,we summarized the molecular features and regulatory functions of these nerves.Finally,we included available translational approaches that utilize nerve function to improve bone homeostasis and promote bone regeneration.Therefore,considering the nervous system within the context of neuromusculoskeletal interactions can deepen our understanding of skeletal homeostasis and repair process,ultimately benefiting future clinical translation.展开更多
Anterior cruciate ligament(ACL)injuries are frequently caused by sports injuries and trauma.In cases involving complete tears,ACL reconstruction(ACLR)surgery is the only way to restore the ligament’s integrity.When s...Anterior cruciate ligament(ACL)injuries are frequently caused by sports injuries and trauma.In cases involving complete tears,ACL reconstruction(ACLR)surgery is the only way to restore the ligament’s integrity.When selecting a graft,both the potential complications and the mechanical properties and healing efficacies should be considered.Artificial ligaments have been widely applied in clinical ACLR,and most have exhibited satisfactory biocompatibility and short-term follow-up results.Compared with autografts and allografts,however,the lack of bioactivity of currently available artificial ligaments is a major disadvantage.In addition,some long-term follow-up results have revealed other drawbacks of artificial ligaments,such as graft failure and other complications.Here,we summarize attempts to enhance the bioactive performance of artificial ligaments,as such modifications may have good potential for clinical translation and could improve the long-term outcomes of existing products.展开更多
Osteoarthritis(OA)is a prevalent degenerative joint disorder marked by chronic pain,inflammation,and cartilage loss,with current treatments limited to symptom relief.G protein-coupled receptors(GPCRs)play a pivotal ro...Osteoarthritis(OA)is a prevalent degenerative joint disorder marked by chronic pain,inflammation,and cartilage loss,with current treatments limited to symptom relief.G protein-coupled receptors(GPCRs)play a pivotal role in OA progression by regulating inflammation,chondrocyte survival,and matrix homeostasis.However,their multifaceted signaling,via G proteins orβ-arrestins,poses challenges for precise therapeutic targeting.Biased agonism,where ligands selectively activate specific GPCR pathways,emerges as a promising approach to optimize efficacy and reduce side effects.This review examines biased signaling in OAassociated GPCRs,including cannabinoid receptors(CB1,CB2),chemokine receptors(CCR2,CXCR4),protease-activated receptors(PAR-2),adenosine receptors(A1R,A2AR,A2BR,A3R),melanocortin receptors(MC1R,MC3R),bradykinin receptors(B2R),prostaglandin E2 receptors(EP-2,EP-4),and calcium-sensing receptors(CaSR).We analyze ligands in clinical trials and explore natural products from Traditional Chinese Medicine as potential biased agonists.These compounds,with diverse structures and bioactivities,offer novel therapeutic avenues.By harnessing biased agonism,this review underscores the potential for developing targeted,safer OA therapies that address its complex pathology,bridging molecular insights with clinical translation.展开更多
Orthopedic conditions have emerged as global health concerns,impacting approximately 1.7 billion individuals worldwide.However,the limited understanding of the underlying pathological processes at the cellular and mol...Orthopedic conditions have emerged as global health concerns,impacting approximately 1.7 billion individuals worldwide.However,the limited understanding of the underlying pathological processes at the cellular and molecular level has hindered the development of comprehensive treatment options for these disorders.The advent of single-cell RNA sequencing(scRNA-seq)technology has revolutionized biomedical research by enabling detailed examination of cellular and molecular diversity.Nevertheless,investigating mechanisms at the single-cell level in highly mineralized skeletal tissue poses technical challenges.In this comprehensive review,we present a streamlined approach to obtaining high-quality single cells from skeletal tissue and provide an overview of existing scRNA-seq technologies employed in skeletal studies along with practical bioinformatic analysis pipelines.By utilizing these methodologies,crucial insights into the developmental dynamics,maintenance of homeostasis,and pathological processes involved in spine,joint,bone,muscle,and tendon disorders have been uncovered.Specifically focusing on the joint diseases of degenerative disc disease,osteoarthritis,and rheumatoid arthritis using scRNA-seq has provided novel insights and a more nuanced comprehension.These findings have paved the way for discovering novel therapeutic targets that offer potential benefits to patients suffering from diverse skeletal disorders.展开更多
Tissue clearing combined with high-resolution confocal imaging is a cutting-edge approach for dissecting the three-dimensional(3D)architecture of tissues and deciphering cellular spatial interactions under physiologic...Tissue clearing combined with high-resolution confocal imaging is a cutting-edge approach for dissecting the three-dimensional(3D)architecture of tissues and deciphering cellular spatial interactions under physiological and pathological conditions.Deciphering the spatial interaction of leptin receptor-expressing(LepR^(+))stromal cells with other compartments in the bone marrow is crucial for a deeper understanding of the stem cell niche and the skeletal tissue.In this study,we introduce an optimized protocol for the 3D analysis of skeletal tissues,enabling the visualization of hematopoietic and stromal cells,especially LepR+stromal cells,within optically cleared bone hemisections.Our method preserves the 3D tissue architecture and is extendable to other hematopoietic sites such as calvaria and vertebrae.The protocol entails tissue fixation,decalcification,and cryosectioning to reveal the marrow cavity.Completed within approximately 12 days,this process yields highly transparent tissues that maintain genetically encoded or antibody-stained fluorescent signals.The bone hemisections are compatible with diverse antibody labeling strategies.Confocal microscopy of these transparent samples allows for qualitative and quantitative image analysis using Aivia or Bitplane Imaris software,assessing a spectrum of parameters.With proper storage,the fluorescent signal in the stained and cleared bone hemisections remains intact for at least 2–3 months.This protocol is robust,straightforward to implement,and highly reproducible,offering a valuable tool for tissue architecture and cellular interaction studies.展开更多
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 treatme...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.展开更多
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 so...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.展开更多
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,t...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.展开更多
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...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.展开更多
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...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.展开更多
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,M...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.展开更多
In this study,perforated cannulated magnesium(Mg)hip stents were fabricated via modified Mg injection molding and conventional machining,respectively.Additionally,the stent canal was filled with paraffin to simulate i...In this study,perforated cannulated magnesium(Mg)hip stents were fabricated via modified Mg injection molding and conventional machining,respectively.Additionally,the stent canal was filled with paraffin to simulate injection of biomaterials.The microstructure,mechanical performance,corrosion behavior,and biocompatibility were comparably studied.Scanning electron microscopy(SEM)and energy dispersive spectroscopy(EDS)showed higher affinity of interstitial element such as oxygen and carbon as consequences of routine molding process.After immersion in SBF,machining stents showed reduced degradation rate and increased deposition of calcium phosphate compared to molding stents.Corrosion resistance was improved via paraffin-filling.Consistently,the hemolysis and in vitro osteoblast cell culture models showed favourable biocompatibility in machining stents compared to molding ones,which was improved by paraffin-filling treatment as well.These results implied that the feasibility of the prepared machining stents as the potential in vivo orthopaedic application where slower degradation is required,which could be enhanced by designing canal-filling injection of biomaterials as well.展开更多
Composite biomaterials made of biodegradable polylactic acid （PLA） and bioactive magnesium （Mg） salt are developed for orthopaedic implants or metal implant coatings. The releasing of Mg salt into the biological e...Composite biomaterials made of biodegradable polylactic acid （PLA） and bioactive magnesium （Mg） salt are developed for orthopaedic implants or metal implant coatings. The releasing of Mg salt into the biological environment benefits the bone growth, while with the releasing of Mg salt and degradation of PLA there forms a porous scaffold for tissue engineering. The size and morphology of the salt and voids are adjustable with such preparation conditions as salt content, pH of casting solution, and the solidification rate, so that we can control the salt releasing and degradation rate of PLA. Dielectric spectroscopy is used to investigate the dispersive structures of Mg salt and voids in the polymer matrix and to monitor the in situ releasing of Mg salts in the simulated body fluid （SBF）. The current study provides us with an orthopedic biomaterial with controllable multi-phase structures, and a tool to investigate the in vivo behaviors of biomaterials.展开更多
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 f...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.展开更多
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 ...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.展开更多
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 ...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.展开更多
The treatment of refractory bone defects is a major clinical challenge,especially in steroid-associated osteonecrosis(SAON),which is characterized by insufficient osteogenesis and angiogenesis.Herin,a microenvironment...The treatment of refractory bone defects is a major clinical challenge,especially in steroid-associated osteonecrosis(SAON),which is characterized by insufficient osteogenesis and angiogenesis.Herin,a microenvironment responsiveness scaffold composed of poly-L-lactide(PLLA),and manganese dioxide(MnO_(2))nanoparticles is designed to enhance bone regeneration by scavenging endogenous reactive oxygen species(ROS)and modulating immune microenvironment in situ.A catalase-like catalytic reaction between MnO_(2)and endogenous hydrogen peroxide(H_(2)O_(2))generated at the bone defect area,which typically becomes acidic and ROS-rich,triggers on-demand release of oxygen and M^(n2+),significantly ameliorating inflammatory response by promoting M2-type polarization of macrophages,reprograming osteoimmune microenvironment conducive to angiogenesis and osteogenesis.Furthermore,the fundamental mechanisms were explored through transcriptome sequencing analysis,revealing that PLLA/MnO_(2)scaffolds(PMns)promote osteogenic differentiation by upre-gulating the TGF-β/Smad signaling pathway in human bone marrow mesenchymal stem cells(hBMSCs).Overall,the PMns exhibit superior immunomodulatory,excellent osteogenic-angiogenic properties and promising can-didates as bone graft substitutes for therapy clinical refractory bone defects.展开更多
Objective:Investigate the combined effects of curcumin and glucosamine on knee function,subchondral bone preservation,and cartilage protection in posttraumatic osteoarthritis(OA)rats.Background:OA increasingly become ...Objective:Investigate the combined effects of curcumin and glucosamine on knee function,subchondral bone preservation,and cartilage protection in posttraumatic osteoarthritis(OA)rats.Background:OA increasingly become a global public health concern.Curcumin and glucosamine,both widely used as dietary supplements for OA,have shown distinct therapeutic effects.However,curcumin’s low bioavailability and the debated efficacy of glucosamine limit their broader clinical use.Methods:Posttraumatic OA was induced in Lewis rats through medial meniscus transection surgery.Rats were treated for 8 weeks with curcumin phospholipid liposome(C,120 mg/kg/d),glucosamine(G,190 mg/kg/d),or a combination of both(CG,C:G=1:3,63/190 mg/kg/d).Knee width was measured weekly,and weight-bearing was assessed twice weekly.Subchondral bone and cartilage changes were analyzed using micro-CT,toluidine blue staining,and the Osteoarthritis Research Society International(OARSI)score.Collagen II expression in cartilage was evaluated by immunohistochemistry.Results:Curcumin phospholipid liposomes significantly reduced joint swelling by up to 4.1%(P<0.001)and improved weight-bearing force by 24.2% at week 2(P<0.01)and 14.9% at week 8(P<0.05)in comparison with the medial meniscus transection group.Analysis of micro-CT indicated an increase in bone volume(BV;11.6%)and bone mineral content(BMC;13.0%)(P<0.05).Histologic analysis showed a 28.8%reduction in OARSI scores(P<0.01)and a 53.1%increase in collagen II expression(P<0.005).Glucosamine treatment reduced joint swelling by up to 5.7%(P<0.0001),improved weight-bearing by 31.6%(P<0.001)at week 2,and significantly increased BV(30.4%)and BMC(29.9%;P<0.05).The combined treatment further reduced swelling by up to 6.6%(P<0.0001)and improved the R/L weight-bearing ratio by 24.7%(P<0.0001)at week 8.It also enhanced BV(28.6%),BMC(29.7%),and anisotropy degree(59.3%;P<0.05).In addition,the combination therapy decreased OARSI scores by 27.1%(P<0.01)and enhanced the expression of collagen II by 54.2%(P<0.005),indicating enhanced cartilage and subchondral bone protection.Conclusion:Curcumin showed superior protection for cartilage,while glucosamine mainly benefited subchondral bone.Combined treatment demonstrated additive effects,improving both knee structure and physical function in OA,offering enhanced pain relief,antiinflammatory action,and joint preservation.展开更多
基金supported by grants from Collaborative Research Fund(Ref:C4032-21GF)General Research Grant(Ref:14114822)+1 种基金Group Research Scheme(Ref:3110146)Area of Excellence(Ref:Ao E/M-402/20)。
文摘Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.
基金supported by the National Natural Science Foundation of China(Grant Nos:82374475 and 82104883,China).
文摘The death of osteoblasts induced by glucocorticoid(GC)-mediated oxidative stress plays a crucial role in the development of steroid-induced osteonecrosis of the femoral head(SIONFH).Improving bone formation driven by osteoblasts has shown promising outcomes in the prognosis of SIONFH.Isovitexin has demonstrated antioxidant properties,but its therapeutic effects on GC-induced oxidative stress and SIONFH remain unexplored.In this study,we analyzed clinical samples obtained from SIONFH patients using proteomic and bioinformatic approaches.
基金supported by the Health&Medical Research Fund(18190481)the General Research Fund(14120520).
文摘The skeleton is innervated by different types of nerves and receives signaling from the nervous system to maintain homeostasis and facilitate regeneration or repair.Although the role of peripheral nerves and signals in regulating bone homeostasis has been extensively investigated,the intimate relationship between the central nervous system and bone remains less understood,yet it has emerged as a hot topic in the bone field.In this review,we discussed clinical observations and animal studies that elucidate the connection between the nervous system and bone metabolism,either intact or after injury.First,we explored mechanistic studies linking specific brain nuclei with bone homeostasis,including the ventromedial hypothalamus,arcuate nucleus,paraventricular hypothalamic nucleus,amygdala,and locus coeruleus.We then focused on the characteristics of bone innervation and nerve subtypes,such as sensory,sympathetic,and parasympathetic nerves.Moreover,we summarized the molecular features and regulatory functions of these nerves.Finally,we included available translational approaches that utilize nerve function to improve bone homeostasis and promote bone regeneration.Therefore,considering the nervous system within the context of neuromusculoskeletal interactions can deepen our understanding of skeletal homeostasis and repair process,ultimately benefiting future clinical translation.
基金supported by the Areas of Excellence Scheme(AoE/M402/20)the Knowledge Transfer Project Fund(KPF24GWP05)+2 种基金the IdeaBooster Fund(IDBF24MED12)the HKSTP Ideation Fund(Ideation 23-0698)the ITC Technology Startup Support Scheme for Universities(TSU24MED05).
文摘Anterior cruciate ligament(ACL)injuries are frequently caused by sports injuries and trauma.In cases involving complete tears,ACL reconstruction(ACLR)surgery is the only way to restore the ligament’s integrity.When selecting a graft,both the potential complications and the mechanical properties and healing efficacies should be considered.Artificial ligaments have been widely applied in clinical ACLR,and most have exhibited satisfactory biocompatibility and short-term follow-up results.Compared with autografts and allografts,however,the lack of bioactivity of currently available artificial ligaments is a major disadvantage.In addition,some long-term follow-up results have revealed other drawbacks of artificial ligaments,such as graft failure and other complications.Here,we summarize attempts to enhance the bioactive performance of artificial ligaments,as such modifications may have good potential for clinical translation and could improve the long-term outcomes of existing products.
基金supported by the National Key R&D Program of the Ministry of Science and Technology(2023YFC2509900)National Natural Science Foundation of China(82374106)+3 种基金National Natural Science Foundation of China(U22A20371)the Basic and Applied Basic Research Fund of Guangdong Province(2021B1515120061)the Shenzhen Science and Technology Innovation Committee(JCYJ20210324102006017)SZ-HK Joint Laboratory for Innovative Biomaterials under CAS-HK Joint Laboratories(2024-2028).
文摘Osteoarthritis(OA)is a prevalent degenerative joint disorder marked by chronic pain,inflammation,and cartilage loss,with current treatments limited to symptom relief.G protein-coupled receptors(GPCRs)play a pivotal role in OA progression by regulating inflammation,chondrocyte survival,and matrix homeostasis.However,their multifaceted signaling,via G proteins orβ-arrestins,poses challenges for precise therapeutic targeting.Biased agonism,where ligands selectively activate specific GPCR pathways,emerges as a promising approach to optimize efficacy and reduce side effects.This review examines biased signaling in OAassociated GPCRs,including cannabinoid receptors(CB1,CB2),chemokine receptors(CCR2,CXCR4),protease-activated receptors(PAR-2),adenosine receptors(A1R,A2AR,A2BR,A3R),melanocortin receptors(MC1R,MC3R),bradykinin receptors(B2R),prostaglandin E2 receptors(EP-2,EP-4),and calcium-sensing receptors(CaSR).We analyze ligands in clinical trials and explore natural products from Traditional Chinese Medicine as potential biased agonists.These compounds,with diverse structures and bioactivities,offer novel therapeutic avenues.By harnessing biased agonism,this review underscores the potential for developing targeted,safer OA therapies that address its complex pathology,bridging molecular insights with clinical translation.
基金National Key Research and Development Program of China(2022YFA1103202)National Natural Science Foundation of China(82272507,32270887,and 32200654)+6 种基金Natural Science Foundation of Chongqing(CSTB2023NSCQ-ZDJO008)Postdoctoral Innovative Talent Support Program(BX20220397)Independent Research Project of State Key Laboratory of Trauma and Chemical Poisoning(SFLKF202201)Project for Enhancing Innovation of Army Medical University(2023X1839)Talent Innovation Training Program at the Army Medical Center(ZXZYTSYS09)General Hospital of Western Theater Command Research Project(2021-XZYG-B10)University Grants Committee,Research Grants Council of Hong Kong,China(14113723,N_CUHK472/22,C7030-18G,T13-402/17-N,and AoE/M-402/20)。
文摘Orthopedic conditions have emerged as global health concerns,impacting approximately 1.7 billion individuals worldwide.However,the limited understanding of the underlying pathological processes at the cellular and molecular level has hindered the development of comprehensive treatment options for these disorders.The advent of single-cell RNA sequencing(scRNA-seq)technology has revolutionized biomedical research by enabling detailed examination of cellular and molecular diversity.Nevertheless,investigating mechanisms at the single-cell level in highly mineralized skeletal tissue poses technical challenges.In this comprehensive review,we present a streamlined approach to obtaining high-quality single cells from skeletal tissue and provide an overview of existing scRNA-seq technologies employed in skeletal studies along with practical bioinformatic analysis pipelines.By utilizing these methodologies,crucial insights into the developmental dynamics,maintenance of homeostasis,and pathological processes involved in spine,joint,bone,muscle,and tendon disorders have been uncovered.Specifically focusing on the joint diseases of degenerative disc disease,osteoarthritis,and rheumatoid arthritis using scRNA-seq has provided novel insights and a more nuanced comprehension.These findings have paved the way for discovering novel therapeutic targets that offer potential benefits to patients suffering from diverse skeletal disorders.
基金National Natural Science Foundation of China(grant number 82272563 to B.S.)National Science and Technology Major Project of the Ministry of Science and Technology of China(grant number 2023ZD0501202 to B.S.)+4 种基金institutional grants allocated to the National Institute of Biological Sciences,Beijing(NIBS)from the Chinese Ministry of Science and Technology,Beijing Municipal Commission of Science and Technology,and Tsinghua Universitythe support from China Pharmaceutical University(grant number 3150140001 to S.F.)National Natural Science Foundation of China(grant numbers 82203653 to S.F.,82371957 to L.W.,and 82371956 to X.C.)Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(grant number JYY2023-8 to X.C.)Research Grants Council of University Grants Committee Hong Kong(grant numbers 14113723,14108720,14121721,14202920,N_CUHK472/22,C7030-18G,T13-402/17-N,and AoE/M-402/20)。
文摘Tissue clearing combined with high-resolution confocal imaging is a cutting-edge approach for dissecting the three-dimensional(3D)architecture of tissues and deciphering cellular spatial interactions under physiological and pathological conditions.Deciphering the spatial interaction of leptin receptor-expressing(LepR^(+))stromal cells with other compartments in the bone marrow is crucial for a deeper understanding of the stem cell niche and the skeletal tissue.In this study,we introduce an optimized protocol for the 3D analysis of skeletal tissues,enabling the visualization of hematopoietic and stromal cells,especially LepR+stromal cells,within optically cleared bone hemisections.Our method preserves the 3D tissue architecture and is extendable to other hematopoietic sites such as calvaria and vertebrae.The protocol entails tissue fixation,decalcification,and cryosectioning to reveal the marrow cavity.Completed within approximately 12 days,this process yields highly transparent tissues that maintain genetically encoded or antibody-stained fluorescent signals.The bone hemisections are compatible with diverse antibody labeling strategies.Confocal microscopy of these transparent samples allows for qualitative and quantitative image analysis using Aivia or Bitplane Imaris software,assessing a spectrum of parameters.With proper storage,the fluorescent signal in the stained and cleared bone hemisections remains intact for at least 2–3 months.This protocol is robust,straightforward to implement,and highly reproducible,offering a valuable tool for tissue architecture and cellular interaction studies.
基金supported by the National Key R&D Program of China(Grant No.2016YFC1102000)the National Natural Science Foundation of China(Grant Nos.81672139 and 81702129)+3 种基金the China Postdoctoral Science Foundation(No.171479)Doctor Initial Foundation of Liaoning Province(No.20170520017)Affiliated Zhongshan Hospital of Dalian University(No.DLDXZSYYDK201701)by a grant from the Research Grants Council of the Hong Kong Special Administrative Region,China(Project No.T13-402/17-N)。
文摘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.
基金supported by the Key-Area Research and Development Program of Guangdong Province(2019B010941001)the Shenzhen Double Chain Project for Innovation and Development Industry supported by the Bureau of Industry and Information Technology of Shenzhen(201908141541)Shenzhen Fundamental Research Foundation(GJHZ20170314154845576 and GJHS20170314161106706).
文摘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.
基金supported by RGC Themebased Research Scheme of Hong Kong (T13-402/17N)National Natural Science Foundation of China (81802152)+5 种基金Natural Science Foundation of Guangdong Province (2019A1515012224)RGC Areas of Excellence (AoE/M-402/20)RGC Collaborative Research Fund (C4026-17WF)General Research Fund (14121918 and 14173917)the Innovation and Technology Commission Funding (ITS/208/18FX)Key-Area Research and Development Program of Guangdong Province (2019B010941001)。
文摘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.
基金National Natural Science Foundation of China(Nos.31970663 and 82173028 to J.X.,No.81874180 to T.W.,No.81201556 to W.Z.,No.82072971 to H.W.and No.81972505 to Z.W.)。
文摘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.
基金supported by grants from the AO Foundation (AOOCD Consortium TA1711481)Areas of Excellence Scheme from the University Grant Council of Hong Kong (Ao E/M-402/20)+1 种基金Theme-based Research Scheme from the University Grant Council of Hong Kong (T13-402/17-N)Key-Area Research and Development Program of Guangdong Province (2019B010941001)
文摘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.
基金Theme-based research scheme of Hong Kong Research Grant Council(RGC Ref:T13-402/17-N)National Natural Science Foundation of China(No.U1804251)。
文摘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.
基金supported by Theme-based Research Scheme(Ref No.T13-402/17-N)Collaborative Research Fund(C402617W)from the Research Grants Council of the Hong Kong Special Administrative Region,ChinaInnovation and Technology Fund(ITS/208/18FX)from the Innovation and Technology Commission of Hong Kong。
文摘In this study,perforated cannulated magnesium(Mg)hip stents were fabricated via modified Mg injection molding and conventional machining,respectively.Additionally,the stent canal was filled with paraffin to simulate injection of biomaterials.The microstructure,mechanical performance,corrosion behavior,and biocompatibility were comparably studied.Scanning electron microscopy(SEM)and energy dispersive spectroscopy(EDS)showed higher affinity of interstitial element such as oxygen and carbon as consequences of routine molding process.After immersion in SBF,machining stents showed reduced degradation rate and increased deposition of calcium phosphate compared to molding stents.Corrosion resistance was improved via paraffin-filling.Consistently,the hemolysis and in vitro osteoblast cell culture models showed favourable biocompatibility in machining stents compared to molding ones,which was improved by paraffin-filling treatment as well.These results implied that the feasibility of the prepared machining stents as the potential in vivo orthopaedic application where slower degradation is required,which could be enhanced by designing canal-filling injection of biomaterials as well.
基金financially supported by the National Natural Scientific Foundation of China(Nos.50773077,20934005 and 51273091)the Hong Kong Special Administration Region Earmarked Projects(CUHK4042/09P,2160396)
文摘Composite biomaterials made of biodegradable polylactic acid （PLA） and bioactive magnesium （Mg） salt are developed for orthopaedic implants or metal implant coatings. The releasing of Mg salt into the biological environment benefits the bone growth, while with the releasing of Mg salt and degradation of PLA there forms a porous scaffold for tissue engineering. The size and morphology of the salt and voids are adjustable with such preparation conditions as salt content, pH of casting solution, and the solidification rate, so that we can control the salt releasing and degradation rate of PLA. Dielectric spectroscopy is used to investigate the dispersive structures of Mg salt and voids in the polymer matrix and to monitor the in situ releasing of Mg salts in the simulated body fluid （SBF）. The current study provides us with an orthopedic biomaterial with controllable multi-phase structures, and a tool to investigate the in vivo behaviors of biomaterials.
基金supported by the National Nature Science Foundation of China(No.81773964)Joint Laboratory for Biomaterials SIAT-HKU-CUHK under CUHK-CAS Joint Laboratory Fund(Project Code:4750376).
文摘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.
基金supported by the collaborative project from the National Key R&D Program of China and Innovation and Tech-nology Fund Mainland-Hong Kong Joint Funding Scheme(Nos.2021YFE0202300 and MHP/011/20)the Sino-Swiss collaborative project from the Ministry of Science and Technology and the Swiss National Science Foundation under the SSSTC program(Grant Nos.2015DFG32200 and 156362)+2 种基金Shenzhen Collaborative Innovation Plan-International Cooperation Project(Grant No.GJHZ20190821160803823)Development and Reform Commission of Shenzhen Municipality(2019)(No.561)Shenzhen Double Chain Project for Innovation and Development Industry supported by Bureau of Industry and Information Technology of Shenzhen(No.201908141541).
文摘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.
文摘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.
基金financially supported by the National Natural Science Foundation of China(81871767)Shenzhen Medical Research Funds(B2302050)+4 种基金Guangdong Basic and Applied Basic Research Foundation(No.2022B1515120046,2023A1515010087,2023A1515011315)Shenzhen Key Laboratory of Digital Surgical Printing Project(ZDSYS201707311542415)Shenzhen Science and Technology Program(JCYJ20220818103417037,JCYJ20210324115814040,JCYJ 20210324102206016,JSGG20210629144538010,KJZD20230923115200002)Shenzhen Development and Reform Program(XMHT20220106001)the Shenzhen Basic Research General Project(JCYJ20220531100408019).
文摘The treatment of refractory bone defects is a major clinical challenge,especially in steroid-associated osteonecrosis(SAON),which is characterized by insufficient osteogenesis and angiogenesis.Herin,a microenvironment responsiveness scaffold composed of poly-L-lactide(PLLA),and manganese dioxide(MnO_(2))nanoparticles is designed to enhance bone regeneration by scavenging endogenous reactive oxygen species(ROS)and modulating immune microenvironment in situ.A catalase-like catalytic reaction between MnO_(2)and endogenous hydrogen peroxide(H_(2)O_(2))generated at the bone defect area,which typically becomes acidic and ROS-rich,triggers on-demand release of oxygen and M^(n2+),significantly ameliorating inflammatory response by promoting M2-type polarization of macrophages,reprograming osteoimmune microenvironment conducive to angiogenesis and osteogenesis.Furthermore,the fundamental mechanisms were explored through transcriptome sequencing analysis,revealing that PLLA/MnO_(2)scaffolds(PMns)promote osteogenic differentiation by upre-gulating the TGF-β/Smad signaling pathway in human bone marrow mesenchymal stem cells(hBMSCs).Overall,the PMns exhibit superior immunomodulatory,excellent osteogenic-angiogenic properties and promising can-didates as bone graft substitutes for therapy clinical refractory bone defects.
基金funded by the Basic and Applied Basic Research Fund of Guangdong Province(2021B1515120061)the Shenzhen Science and Technology Innovation Committee(JCYJ20210324102006017)+3 种基金SZ-HK Joint Laboratory for Innovative Biomaterials under CAS-HK Joint Laboratories(2024-2028)The Science and Technology Development Fund,Macao SAR(file no.005/2023/SKL)funded by Sirio Pharma Co.,Ltdfunding from Sirio Pharma Co.,Ltd.
文摘Objective:Investigate the combined effects of curcumin and glucosamine on knee function,subchondral bone preservation,and cartilage protection in posttraumatic osteoarthritis(OA)rats.Background:OA increasingly become a global public health concern.Curcumin and glucosamine,both widely used as dietary supplements for OA,have shown distinct therapeutic effects.However,curcumin’s low bioavailability and the debated efficacy of glucosamine limit their broader clinical use.Methods:Posttraumatic OA was induced in Lewis rats through medial meniscus transection surgery.Rats were treated for 8 weeks with curcumin phospholipid liposome(C,120 mg/kg/d),glucosamine(G,190 mg/kg/d),or a combination of both(CG,C:G=1:3,63/190 mg/kg/d).Knee width was measured weekly,and weight-bearing was assessed twice weekly.Subchondral bone and cartilage changes were analyzed using micro-CT,toluidine blue staining,and the Osteoarthritis Research Society International(OARSI)score.Collagen II expression in cartilage was evaluated by immunohistochemistry.Results:Curcumin phospholipid liposomes significantly reduced joint swelling by up to 4.1%(P<0.001)and improved weight-bearing force by 24.2% at week 2(P<0.01)and 14.9% at week 8(P<0.05)in comparison with the medial meniscus transection group.Analysis of micro-CT indicated an increase in bone volume(BV;11.6%)and bone mineral content(BMC;13.0%)(P<0.05).Histologic analysis showed a 28.8%reduction in OARSI scores(P<0.01)and a 53.1%increase in collagen II expression(P<0.005).Glucosamine treatment reduced joint swelling by up to 5.7%(P<0.0001),improved weight-bearing by 31.6%(P<0.001)at week 2,and significantly increased BV(30.4%)and BMC(29.9%;P<0.05).The combined treatment further reduced swelling by up to 6.6%(P<0.0001)and improved the R/L weight-bearing ratio by 24.7%(P<0.0001)at week 8.It also enhanced BV(28.6%),BMC(29.7%),and anisotropy degree(59.3%;P<0.05).In addition,the combination therapy decreased OARSI scores by 27.1%(P<0.01)and enhanced the expression of collagen II by 54.2%(P<0.005),indicating enhanced cartilage and subchondral bone protection.Conclusion:Curcumin showed superior protection for cartilage,while glucosamine mainly benefited subchondral bone.Combined treatment demonstrated additive effects,improving both knee structure and physical function in OA,offering enhanced pain relief,antiinflammatory action,and joint preservation.
