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Bioactive Materials 2021年第5期6卷 1353-1364页

作者： Meiling Zhu Kunyu Zhang Lu Feng sien lin Qi Pan Liming Bian Gang Li Department of Orthopaedics&Traumatology Faculty of MedicineThe Chinese University of Hong KongPrince of Wales HospitalShatinHong KongSARPR China Stem Cells and Regenerative Medicine Laboratory Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongPrince of Wales HospitalShatinSARHong KongPR China The Eighth Affiliated Hospital Sun Yat-Sen UniversityShenzhenPR China Department of Biomedical Engineering The Chinese University of Hong KongHong KongSARPR China Shenzhen Research Institute The Chinese University of Hong KongShenzhenPR China Centre of Novel Biomaterials The Chinese University of Hong KongHong KongSARPR China

Research works on the synergistic effect of surface modified bioactive molecules and bone metal implants have been highlighted.N-cadherin is regarded as a key factor in directing cell-cell interactions during the mesenchymal condensation preceding the osteogenesis in the musculoskeletal *** this study,the N-cadherin mimetic peptide(Cad)was biofunctionalized on the titanium metal surface via the acryloyl bisphosphonate(Ac-BP).To learn the synergistic effect of N-cadherin mimetic peptide,when tethered with titanium substrates,on promoting osteogenic differentiation of the seeded human mesenchymal stem cells(hMSCs)and the osseointegration at the bone-implant *** show that the conjugation of N-cadherin mimetic peptide with Ac-BP promoted the osteogenic gene markers expression in the *** biofunctionalized biomaterial surfaces promote the expression of the Wnt/β-catenin downstream axis in the attached hMSCs,and then enhance the in-situ bone formation and osseointegration at the bone-implant *** conclude that this N-cadherin mimetic peptide tethered on Ti surface promote osteogenic differentiation of hMSCs and osseointegration of biomaterial implants in vitro and in *** findings demonstrate the importance of the development-inspired surface bioactivation of metal implants and shed light on the possible cellular mechanisms of the enhanced osseointegration.

关键词： N-cadherin mimetic peptide Mesenchymal condensation Osseointegration Wnt/β-catenin signaling Titanium dioxide(TiO2)

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Bone Research 2024年第3期12卷 502-516页

作者： Bobin Mi Yuan Xiong Samuel Knoedler Michael Alfertshofer Adriana C.Panayi Haixing Wang sien lin Gang Li Guohui Liu Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and Technology1277 Jiefang AvenueWuhan 430022China Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration Wuhan 430022China Division of Plastic Surgery Department of SurgeryBrigham and Women’s HospitalHarvard Medical SchoolBostonMAUSA Institute of Regenerative Biology and Medicine Helmholtz Zentrum MünchenMunichGermany Division of Hand Plastic and Aesthetic SurgeryLudwig-Maximilian University MunichMunichGermany Department of Hand- Plastic and Reconstructive SurgeryMicrosurgeryBurn Trauma CenterBG Trauma Center LudwigshafenUniversity of HeidelbergLudwigshafenGermany Department of Orthopaedics&Traumatology Stem Cells and Regenerative Medicine LaboratoryLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongPrince of Wales HospitalShatinHong KongSAR 999077P.R.China

Ageing as a natural irreversible process inherently results in the functional deterioration of numerous organ systems and tissues,including the skeletal and immune *** studies have elucidated the intricate bidirection... 详细信息

关键词： skeleton insight irreversible

Hallmarks of peripheral nerve function in bone regeneration

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Bone Research 2023年第1期11卷 47-64页

作者： Ranyang Tao Bobin Mi Yiqiang Hu sien lin Yuan Xiong Xuan Lu Adriana C.Panayi Gang Li Guohui Liu Department of Orthopaedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022P.R.China Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration Wuhan430022P.R.China Department of Orthopaedics&Traumatology Stem Cells and Regenerative Medicine LaboratoryLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongPrince of Wales HospitalShatinHong KongSAR999077P.R.China Division of Plastic Surgery Brigham and Women’s HospitalHarvard Medical SchoolBoston02215MAUSA

Skeletal tissue is highly *** different types of nerves have been recently identified in the bone,the crosstalk between bone and nerves remains *** this review,we outline the role of the peripheral nervous system(PNS)in bone regeneration following *** first introduce the conserved role of nerves in tissue regeneration in species ranging from amphibians to *** then present the distribution of the PNS in the skeletal system under physiological conditions,fractures,or ***,we summarize the ways in which the PNS communicates with bone-lineage cells,the vasculature,and immune cells in the bone *** on this comprehensive and timely review,we conclude that the PNS regulates bone regeneration through neuropeptides or neurotransmitters and cells in the peripheral *** in-depth understanding of the roles of peripheral nerves in bone regeneration will inform the development of new strategies based on bone-nerve crosstalk in promoting bone repair and regeneration.

关键词： nerves regeneration function

Histone demethylase Kdm5c regulates osteogenesis and bone formation via PI3K/Akt/HIF1α and Wnt/β-catenin signaling pathways

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Genes & Diseases 2024年第1期11卷 64-66页

作者： Ying Li lingli Ding Yage Zhang Bingyu Zhou Gene Chi Wai Man Min Wang Jinglan Li Yamei Liu Weiping lin Haibin Wang sien lin Liangliang Xu Key Laboratory of Orthopaedics&Traumatology Lingnan Medical Research CenterThe First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou University of Chinese MedicineGuangzhouGuangdong 510000China Department of Orthopaedics&Traumatology Faculty of MedicineThe Chinese University of Hong KongPrince of Wales HospitalShatinHong Kong SAR 999077China Departments of Diagnostics of Traditional Chinese Medicine Guangzhou University of Chinese MedicineGuangzhouGuangdong 510000China Orthopaedic Research Lab Affiliated Hospital of Guangdong Medical UniversityGuangdong Medical UniversityZhanjiangGuangdong 524001China

Fractures have an extraordinarily negative impact on individuals'quality of life and functional *** or disability of fracture is a major health issue with important clinical,social,and economic implications.1 Mesenchymal stem cells(MSCs)play an indispensable role in the initiation of the fracture repair process including the formation of a callus which is replaced by new *** use of MSCs in the treatment of fractures is very attractive as they can reduce the time of healing and occurrence of nonunion.

关键词： PI3K/Akt HIF1α healing

Dual-response of multi-functional microsphere system to ultrasound and microenvironment for enhanced bone defect treatment

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Bioactive Materials 2024年第2期32卷 304-318页

作者： Qingxu Song Dianwei Wang Haoyu Li Zongliang Wang Songjia Sun Zhenyu Wang Yi Liu sien lin Gang Li Shaokun Zhang Peibiao Zhang Department of Spine Surgery The First Hospital of Jilin UniversityChangchun130021China Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun130022China Department of Dermatology Second Hospital of Jilin UniversityChangchun130022China Department of Orthopaedics and Traumatology and Li Ka Shing Institute of Health Sciences Prince of Wales HospitalThe Chinese University of Hong KongShatinHong Kong Special Administrative Region of China

Using bone tissue engineering strategies to achieve bone defect repair is a promising ***,the repair process outcomes are often *** we properly designed a multi-functional microsphere system,which could deliver bioactive proteins under the dual response of ultrasound and microenvironment,release microenvironment-responsive products on demand,reverse bone injury microenvironment,regulate the immune microenvironment,and achieve excellent bone defect treatment *** particular,the MnO_(2) introduced into the poly(lactic-co-glycolic acid)(PLGA)microspheres during synthesis could consume the acid produced by the degradation of PLGA to protect bone morphogenetic protein-2(BMP-2).More importantly,MnO_(2) could consume reactive oxygen species(ROS)and produce Mn^(2+)and oxygen(O_(2)),further promoting the repair of bone defects while reversing the ***,the reversal of the bone injury microenvironment and the depletion of ROS promoted the polarization of M1 macrophages to M2 macrophages,and the immune microenvironment was ***,the ultrasound(US)irradiation used during treatment also allowed the on-demand release of microenvironment-responsive *** multi-functional microsphere system combines the effects of on-demand delivery,reversal of bone injury microenvironment,and regulation of the immune microenvironment,providing new horizons for the clinical application of protein delivery and bone defect repair.

关键词： BMP-2 Multi-functional microsphere Bone defect repair Bone injury microenvironment Immune microenvironment

A bioactive compliant vascular graft modulates macrophage polarization and maintains patency with robust vascular remodeling

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Bioactive Materials 2023年第1期19卷 167-178页

作者： Alexander Stahl Dake Hao Janos Barrera Dominic Henn sien lin Seyedsina Moeinzadeh Sungwoo Kim William Maloney Geoffrey Gurtner Aijun Wang Yunzhi Peter Yang Department of Orthopaedic Surgery Stanford University240 Pasteur DriveStanfordCA94304USA Department of Chemistry Stanford University121 Mudd BuildingStanfordCA94305USA Department of Surgery School of MedicineUniversity of California DavisSacramentoCA95817USA Institute for Pediatric Regenerative Medicine Shriners Hospitals for ChildrenSacramentoCA95817USA Department of Surgery Stanford University300 Pasteur DriveStanfordCA94305USA Department of Biomedical Engineering University of California DavisDavisCA95616USA Department of Materials Science and Engineering Stanford University496 Lomita MallStanfordCA94305USA Department of Bioengineering Stanford University443 Via OrtegaStanfordCA4305USA

Conventional synthetic vascular grafts are associated with significant failure rates due to their mismatched mechanical properties with the native vessel and poor regenerative *** different tissue engineering approaches have been used to improve the biocompatibility of synthetic vascular grafts,it is still crucial to develop a new generation of synthetic grafts that can match the dynamics of native vessel and direct the host response to achieve robust vascular *** size of pores within implanted biomaterials has shown significant effects on macrophage polarization,which has been further confirmed as necessary for efficient vascular formation and ***,we developed biodegradable,autoclavable synthetic vascular grafts from a new polyurethane elastomer and tailored the grafts’interconnected pore sizes to promote macrophage populations with a pro-regenerative phenotype and improve vascular regeneration and patency *** synthetic vascular grafts showed similar mechanical properties to native blood vessels,encouraged macrophage populations with varying M2 to M1 phenotypic expression,and maintained patency and vascular regeneration in a one-month rat carotid interposition model and in a four-month rat aortic interposition *** innovative bioactive synthetic vascular graft holds promise to treat clinical vascular diseases.

关键词： Vascular graft Vascular compliance Pore size Macrophage polarization Vascular remodeling

Augmenting osteoporotic bone regeneration through a hydrogel-based rejuvenating microenvironment

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Bioactive Materials 2024年第11期41卷 440-454页

作者： Xiaoting Zhang Boguang Yang Lu Feng Xiayi Xu Chenmin Wang Yuk-wai Lee Ming Wang Xuan Lu ling Qin sien lin Liming Bian Gang Li Musculoskeletal Research Laboratory Department of Orthopaedics&TraumatologyThe Chinese University of Hong KongPrince of Wales HospitalHong KongChina Stem Cells and Regenerative Medicine Laboratory Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongPrince of Wales HospitalHong KongChina The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System The Chinese University of Hong Kong Shenzhen Research InstituteShenzhenPR China SH Ho Scoliosis Research Laboratory Department of Orthopaedics and TraumatologyThe Chinese University of Hong KongHong KongChina Joint Scoliosis Research Center of the Chinese University of Hong Kong and Nanjing University The Chinese University of Hong KongHong KongChina Li Ka Shing Institute of Health Sciences The Chinese University of Hong KongChina School of Biomedical Sciences and Engineering Guangzhou International CampusSouth China University of TechnologyGuangzhou511442PR China Department of Orthopaedics and Traumatology The University of Hong KongHong KongChina

Osteoporotic bone defects pose a significant challenge for bone regeneration as they exhibit impaired healing capacity and delayed healing *** address this issue,this study introduces a hydrogel that creates a rejuvenating microenvironment,thereby facilitating efficient bone repair during the initial two weeks following bone defect *** hydrogel,named GelHFS,was created through host-guest polymerization of gelatin and acrylatedβ-*** of the human fetal mesenchymal stem cell secretome(HFS)formed GelHFS hydrogel aimed at mimicking a rejuvenated stem cell *** results demonstrated that GelHFS hydrogel promotes cell stellate spreading and osteogenic differentiation via integrinβ1-induced focal adhesion *** of GelHFS hydrogel in an osteoporotic bone defect rat model recruited endogenous integrinβ1-expressing cells and enhanced new bone formation and bone *** findings reveal that GelHFS hydrogel provides a rejuvenating niche for endogenous MSCs and enhances bone regeneration in osteoporotic bone *** findings highlight the potential of GelHFS hydrogel as an effective therapeutic strategy for addressing challenging bone healing such as osteoporotic bone regeneration.

关键词： Osteoporotic bone defects Bone regeneration Rejuvenating microenvironment Secretome Focal adhesion pathway

Enhancing cartilage repair with optimized supramolecular hydrogel-based scaffold and pulsed electromagnetic field

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Bioactive Materials 2023年第4期22卷 312-324页

作者： Yucong Li linlong Li Ye Li Lu Feng Bin Wang Ming Wang Haixing Wang Meiling Zhu Yongkang Yang Erik IWaldorff Nianli Zhang Ingmar Viohl sien lin Liming Bian Wayne Yuk-Wai Lee Gang Li Department of Orthopaedics&Traumatology Stem Cells and Regenerative Medicine LaboratoryLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongPrince of Wales HospitalShatinHong Kong Special Administrative Region Research&Clinical Affairs Orthofix Medical Inc.LewisvilleTXUSA Department of Rehabilitation Sciences Hong Kong Polytechnic UniversityHong Kong Special Administrative Region Innovation Centre for Advanced Interdisciplinary Medicine Key Laboratory of Biological Targeting DiagnosisTherapy and Rehabilitation of Guangdong Higher Education InstitutesThe Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina The Eighth Affiliated Hospital Sun Yat-Sen UniversityShenzhenPR China School of Biomedical Sciences and Engineering National Engineering Research Center for Tissue Restoration and ReconstructionKey Laboratory of Biomedical Materials and Engineering of the Ministry of EducationSouth China University of TechnologyGuangzhouPR China Department of Orthopaedics and Traumatology SH Ho Scoliosis Research LaboratoryJoint Scoliosis Research Center of the Chinese University of Hong Kong and Nanjing UniversityThe Chinese University of Hong KongHong Kong Special Administrative Region

Functional tissue engineering strategies provide innovative approach for the repair and regeneration of damaged *** is widely used because it could provide rapid defect filling and proper structure support,and is biocompatible for cell aggregation and matrix *** have been made to seek suitable scaffolds for cartilage tissue *** Alg-DA/Ac-β-CD/gelatin hydrogel was designed with the features of physical and chemical multiple crosslinking and self-healing *** time,swelling ratio,biodegradability and biocompatibility of the hydrogels were systematically characterized,and the injectable self-healing adhesive hydrogel were demonstrated to exhibit ideal properties for cartilage ***,the new hydrogel design introduces a pre-gel state before photo-crosslinking,where increased viscosity and decreased fluidity allow the gel to remain in a semi-solid *** granted multiple administration routes to the hydrogels,which brings hydrogels the ability to adapt to complex clinical *** electromagnetic fields(PEMF)have been recognized as a promising solution to various health problems owing to their noninvasive properties and therapeutic *** treatment offers a better clinical outcome with fewer,if any,side effects,and wildly used in musculoskeletal tissue *** we propose PEMF as an effective biophysical stimulation to be 4th key element in cartilage tissue *** this study,the as-prepared Alg-DA/Ac-β-CD/gelatin hydrogels were utilized in the rat osteochondral defect model,and the potential application of PEMF in cartilage tissue engineering were *** treatment were proven to enhance the quality of engineered chondrogenic constructs in vitro,and facilitate chondrogenesis and cartilage repair in *** of the results suggested that with the injectable self-healing adhesive hydrogel and PEMF treatment,this newly proposed tissue engineering strategy r

关键词： Supramolecular hydrogels Pulsed electromagnetic field Cartilage tissue engineering Mesenchymal stem cells Chondrogenesis

脂肪来源的干细胞复合壳聚糖支架促进大鼠颅骨缺损修复的实验研究

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重庆医科大学学报 2020年第2期45卷 161-166页

作者：黄健萍林思恩兰青广东医科大学附属医院口腔科湛江524001 广东医科大学附属医院骨科中心湛江524001

目的:探讨以脂肪来源的干细胞(adipose-derived stem cells,ADSCs)为基础构建组织工程生物材料修复大鼠颅骨缺损的效果。方法:分离、培养ADSCs,并进行成骨、成脂、成软骨三系分化。制备壳聚糖多孔支架,扫描电镜观察接种ADSCs前后的微结... 详细信息

目的:探讨以脂肪来源的干细胞(adipose-derived stem cells,ADSCs)为基础构建组织工程生物材料修复大鼠颅骨缺损的效果。方法:分离、培养ADSCs,并进行成骨、成脂、成软骨三系分化。制备壳聚糖多孔支架,扫描电镜观察接种ADSCs前后的微结构变化,以细胞活力试剂盒测试ADSCs接种于壳聚糖多孔支架后的细胞活力。取15只雄性Sprague Dawley(SD)大鼠予手术制备颅骨缺损模型,将缺损留空或植入壳聚糖支架,壳聚糖支架表面预先种植低密度(2.5×10~5)或高密度(1×10~6)ADSCs。术后8周收集样品用于微型计算机断层扫描分析,随后脱钙,石蜡包埋切片后行苏木素-伊红染色和免疫组化染色观察成骨指标骨涎蛋白。结果:ADSCs可以成功诱导成骨、成软骨和成脂肪分化;扫描电镜和细胞活力测试结果提示壳聚糖支架呈现多孔结构,ADSCs可黏附于支架并增殖,增殖效果与普通培养板相比无统计学差异。在大鼠颅骨缺损模型中,高密度ADSCs/壳聚糖支架组骨组织体积百分数分别比空白对照组和低密度ADSCs/壳聚糖支架组升高140.8%(P=0.014)和37.4%(P=0.036)。与空白缺损对照组相比,低密度ADSCs/壳聚糖支架组和高密度ADSCs/壳聚糖支架组骨密度分别升高29.4%(P=0.123)和64.1%(P=0.022)。组织学结果表明,骨缺损区新生骨组织的分布和数量与微型计算机断层扫描分析结果一致。成骨分化指标骨涎蛋白在高密度组表达有增高趋势。结论:高密度ADSCs复合壳聚糖支架可有效修复大鼠的颅骨缺损。

关键词：脂肪间充质干细胞组织工程学壳聚糖支架颅骨缺损