Coal is the dominant primary energy source in China and the major source of greenhouse gases and air pollutants. To facilitate the use of coal in an environmentally satisfactory and economically viable way, clean coal...Coal is the dominant primary energy source in China and the major source of greenhouse gases and air pollutants. To facilitate the use of coal in an environmentally satisfactory and economically viable way, clean coal technologies （CCTs） are necessary. This paper presents a review of recent research and development of four kinds of CCTs： coal power generation; coal conversion; pollution control; and carbon capture, utilization, and storage. It also outlines future perspectives on directions for technology re search and development （R＆D）. This review shows that China has made remarkable progress in the R＆D of CCTs, and that a number of CCTs have now entered into the commercialization stage.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
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 order to investigate the problem of long-term strength retrogression in oil well cement systems exposed to high pressure and high temperature(HPHT)curing conditions,various influencing factors,including cement sour...In order to investigate the problem of long-term strength retrogression in oil well cement systems exposed to high pressure and high temperature(HPHT)curing conditions,various influencing factors,including cement sources,particle sizes of silica flour,and additions of silica fume,alumina,colloidal iron oxide and nano-graphene,were investigated.To simulate the environment of cementing geothermal wells and deep wells,cement slurries were directly cured at 50 MPa and 200?C.Mineral compositions(as determined by X-ray diffraction Rietveld refinement),water permeability,compressive strength and Young’s modulus were used to evaluate the qualities of the set cement.Short-term curing(2e30 d)test results indicated that the adoption of 6 m m ultrafine crystalline silica played the most important role in stabilizing the mechanical properties of oil well cement systems,while the addition of silica fume had a detrimental effect on strength stability.Long-term curing(2e180 d)test results indicated that nano-graphene could stabilize the Young’s modulus of oil well cement systems.However,none of the ad-mixtures studied here can completely prevent the strength retrogression phenomenon due to their inability to stop the conversion of amorphous to crystalline phases.展开更多
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 synth...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.展开更多
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-t...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.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
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 associ...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.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
Magnesium metal and its alloys are being developed as effective orthopedic implants;however,the mechanisms underlying the actions of magnesium on bones remain unclear.Cystic fibrosis,the most common genetic disease in...Magnesium metal and its alloys are being developed as effective orthopedic implants;however,the mechanisms underlying the actions of magnesium on bones remain unclear.Cystic fibrosis,the most common genetic disease in Caucasians caused by the mutation of CFTR,has shown bone disorder as a key clinical manifestation,which currently lacks effective therapeutic options.Here we report that implantation of magnesium-containing implant stimulates bone formation and improves bone fracture healing in CFTR-mutant mice.Wnt/β-catenin signaling in the bone is enhanced by the magnesium implant,and inhibition of Wnt/β-catenin by iCRT14 blocks the magnesium implant to improve fracture healing in CFTR-mutant mice.We further demonstrate that magnesium ion enters osteocytes,increases intracellular cAMP level and activates ATF4,a key transcription factor known to regulate Wnt/β-catenin signaling.In vivo knockdown of ATF4 abolishes the magnesium implant-activated β-catenin in bones and reverses the improved-fracture healing in CFTR-mutant mice.In addition,oral supplementation of magnesium activates ATF4 and β-catenin as well as enhances bone volume and density in CFTR-mutant mice.Together,these results show that magnesium implantation or supplementation may serve as a potential anabolic therapy for cystic fibrosis-related bone disease.Activation of ATF4-dependent Wnt/β-catenin signaling in osteocytes is identified as a previously undefined mechanism underlying the beneficial effect of magnesium on bone formation.展开更多
基金Acknowledgements The authors gratefully acknowledge the funding support from the National Key Basic Research Program of China （2013CB228500）, the National Natural Science Foundation of Chi- na （71203119）, and the Advanced Coal Technology Consortium of CERC （2016YFE0102500）.
文摘Coal is the dominant primary energy source in China and the major source of greenhouse gases and air pollutants. To facilitate the use of coal in an environmentally satisfactory and economically viable way, clean coal technologies （CCTs） are necessary. This paper presents a review of recent research and development of four kinds of CCTs： coal power generation; coal conversion; pollution control; and carbon capture, utilization, and storage. It also outlines future perspectives on directions for technology re search and development （R＆D）. This review shows that China has made remarkable progress in the R＆D of CCTs, and that a number of CCTs have now entered into the commercialization stage.
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Financial support comes from China National Natural Science Foundation(Grant No.51974352)as well as from China University of Petroleum(East China)(Grant Nos.2018000025 and 2019000011)。
文摘In order to investigate the problem of long-term strength retrogression in oil well cement systems exposed to high pressure and high temperature(HPHT)curing conditions,various influencing factors,including cement sources,particle sizes of silica flour,and additions of silica fume,alumina,colloidal iron oxide and nano-graphene,were investigated.To simulate the environment of cementing geothermal wells and deep wells,cement slurries were directly cured at 50 MPa and 200?C.Mineral compositions(as determined by X-ray diffraction Rietveld refinement),water permeability,compressive strength and Young’s modulus were used to evaluate the qualities of the set cement.Short-term curing(2e30 d)test results indicated that the adoption of 6 m m ultrafine crystalline silica played the most important role in stabilizing the mechanical properties of oil well cement systems,while the addition of silica fume had a detrimental effect on strength stability.Long-term curing(2e180 d)test results indicated that nano-graphene could stabilize the Young’s modulus of oil well cement systems.However,none of the ad-mixtures studied here can completely prevent the strength retrogression phenomenon due to their inability to stop the conversion of amorphous to crystalline phases.
基金support from Hong Kong RGC Theme-based Research Scheme(T13-402/17-N)National Natural Science Foundation of China(81802152)+1 种基金Collaborative Research Fund(C4026-17WF)Health and Medical Research Fund(17180671).
文摘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.
基金supported by the Areas of Excellence Scheme from University Grant Council of Hong Kong(AoE/M-402/20)the AO Foundation,Switzerland(AO-OCD Consortium TA1711481)+1 种基金the Theme-based Research Scheme from University Grant Council of Hong Kong(T13-402/17-N)the Mainland-Hong Kong Joint Funding Scheme of Innovation and Technology Fund:ITF MHKJFS(MHP/011/20).
文摘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.
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supported by Theme-based Research Scheme from RGC-Hong Kong(No.T13-402/17N)partially supported by Health and Medical Research Fund(17180671)National Natural Science Foundation of China(81802152).
文摘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.
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supported in part by Theme-based Research Scheme of Hong Kong(No.T13-402/17 N)Health and Medical Research Fund of Hong Kong(15161441 and 18190481)+3 种基金Early Career Scheme of Hong Kong(No.24104517)Start-up fund at the Hong Kong Polytechnic UniversityNational Natural Science Foundation of China(81802152)Natural Science Foundation of Guangdong Province(2019A1515012224 and 2021A1515011204).
文摘Magnesium metal and its alloys are being developed as effective orthopedic implants;however,the mechanisms underlying the actions of magnesium on bones remain unclear.Cystic fibrosis,the most common genetic disease in Caucasians caused by the mutation of CFTR,has shown bone disorder as a key clinical manifestation,which currently lacks effective therapeutic options.Here we report that implantation of magnesium-containing implant stimulates bone formation and improves bone fracture healing in CFTR-mutant mice.Wnt/β-catenin signaling in the bone is enhanced by the magnesium implant,and inhibition of Wnt/β-catenin by iCRT14 blocks the magnesium implant to improve fracture healing in CFTR-mutant mice.We further demonstrate that magnesium ion enters osteocytes,increases intracellular cAMP level and activates ATF4,a key transcription factor known to regulate Wnt/β-catenin signaling.In vivo knockdown of ATF4 abolishes the magnesium implant-activated β-catenin in bones and reverses the improved-fracture healing in CFTR-mutant mice.In addition,oral supplementation of magnesium activates ATF4 and β-catenin as well as enhances bone volume and density in CFTR-mutant mice.Together,these results show that magnesium implantation or supplementation may serve as a potential anabolic therapy for cystic fibrosis-related bone disease.Activation of ATF4-dependent Wnt/β-catenin signaling in osteocytes is identified as a previously undefined mechanism underlying the beneficial effect of magnesium on bone formation.
