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Engineered polycaprolactone–magnesium hybrid biodegradable porous scaffold for bone tissue engineering

Progress in Natural Science:Materials International 2014年第5期24卷 561-567页

作者： Hoi Man Wong Paul K.Chu Frankie K.L.Leung Kenneth M.C.Cheung Keith D.K.Luk Kelvin W.K.Yeung Department of orthopaedics and traumatology The University of Hong Kong shenzhen key laboratory for innovative technology in orthopaedic trauma The University of Hong Kong Shenzhen Hospital Department of Physics and Materials Science City University of Hong Kong Peking University shenzhen Institution

In this paper, we describe the fabrication of a new biodegradable porous scaffold composed of polycaprolactone(PCL) and magnesium(Mg)micro-particles. The compressive modulus of PCL porous scaffold was increased to at least 150% by incorporating 29% Mg particles with the porosity of 74% using Micro-CT analysis. Surprisingly, the compressive modulus of this scaffold was further increased to at least 236% when the silane-coupled Mg particles were added. In terms of cell viability, the scaffold modified with Mg particles significantly convinced the attachment and growth of osteoblasts as compared with the pure PCL scaffold. In addition, the hybrid scaffold was able to attract the formation of apatite layer over its surface after 7 days of immersion in normal culture medium, whereas it was not observed on the pure PCL scaffold. This in vitro result indicated the enhanced bioactivity of the modified scaffold. Moreover, enhanced bone forming ability was also observed in the rat model after 3 months of implantation. Though bony in-growth was found in all the implanted scaffolds. High volume of new bone formation could be found in the Mg/PCL hybrid scaffolds when compared to the pure PCL scaffold. Both pure PCL and Mg/PCL hybrid scaffolds were degraded after 3 months. However, no tissue inflammation was observed. In conclusion, these promising results suggested that the incorporation of Mg micro-particles into PCL porous scaffold could significantly enhance its mechanical and biological properties. This modified porous bio-scaffold may potentially apply in the surgical management of large bone defect fixation.

关键词： Magnesium Polycaprolactone Biodegradability Biocompatibility Mechanical properties

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Influence of screw length and diameter on tibial strain energy density distribution after anterior cruciate ligament reconstruction

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Acta Mechanica Sinica 2014年第2期30卷 241-249页

作者： Jie Yao Guan-Ming Kuang Duo Wai-Chi Wong Wen-Xin Niu Ming Zhang Yu-Bo Fan key laboratory for Biomechanics and Mechanobiology of Ministry of Education School of Biological Science and Medical Engineering/National Key Lab of Virtual Reality TechnologyBeihang University Interdisciplinary Division of Biomedical Engineering Faculty of EngineeringThe Hong Kong Polytechnic University shenzhen key laboratory for innovative technology in orthopaedic trauma Department of Orthopaedics and TraumatologyThe University of Hong Kong-Shenzhen Hospital The University of Hong Kong Tongji University School of Medicine

Postoperative tunnel enlargement has been frequently reported after anterior cruciate ligament（ACL）*** screw,as a surgical implant in ACL reconstruction,may influence natural loading transmission and contribute to tunnel *** aims of this study are（1）to quantify the alteration of strain energy density（SED）distribution after the anatomic single-bundle ACL reconstruction;and（2）to characterize the influence of screw length and diameter on the degree of the SED alteration.A validated finite element model of human knee joint was *** screw length ranging from 20 to 30 mm with screw diameter ranging from 7 to 9 mm were *** the post-operative knee,the SED increased steeply at the extra-articular tunnel aperture under compressive and complex loadings,whereas the SED decreased beneath the screw shaft and nearby the intra-articular tunnel *** the screw length could lower the SED deprivation in the proximal part of the bone tunnel;whereas increasing either screw length or diameter could aggravate the SED deprivation in the distal part of the bone *** the elastic modulus of the screw could lower the bone SED deprivation around the *** consideration of both graft stability and SED alteration,a biodegradable interference screw with a long length is recommended,which could provide a beneficial mechanical environment at the distal part of the tunnel,and meanwhile decrease the bone-graft motion and synovial fluid propagation at the proximal part of the *** findings together with the clinical and histological factors could help to improve surgical outcome,and serve as a preliminary knowledge for the following study of biodegradable interference screw.

关键词： Anterior crucial ligament reconstruction Strain energy density Screw length Screw diameter

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Bone grafts and biomaterials substitutes for bone defect repair:A review

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Bioactive Materials 2017年第4期2卷 224-247页

作者： Wenhao Wang Kelvin W.K.Yeung Department of orthopaedics and traumatology The University of Hong KongPokfulamHong KongChina shenzhen key laboratory for innovative technology in orthopaedic trauma The University of Hong Kong Shenzhen Hospital1 Haiyuan 1st RoadFutian DistrictShenzhenChina

Bone grafts have been predominated used to treat bone defects,delayed union or non-union,and spinal fusion in orthopaedic clinically for a period of time,despite the emergency of synthetic bone graft ***,the integration of allogeneic grafts and synthetic substitutes with host bone was found jeopardized in long-term follow-up ***,the enhancement of osteointegration of these grafts and substitutes with host bone is considerably *** address this problem,addition of various growth factors,such as bone morphogenetic proteins(BMPs),parathyroid hormone(PTH)and platelet rich plasma(PRP),into structural allografts and synthetic substitutes have been *** clinical applications of these factors have exhibited good bone formation,their further application was limited due to high cost and potential adverse side ***,bioinorganic ions such as magnesium,strontium and zinc are considered as alternative of osteogenic biological ***,this paper aims to review the currently available bone grafts and bone substitutes as well as the biological and bio-inorganic factors for the treatments of bone defect.

关键词： Fracture healing Bone grafts and substitutes Growth factors Bioinorganic ions

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Nanograins on Ti-25Nb-3Mo-2Sn-3Zr alloy facilitate fabricating biological surface through dual-ion implantation to concurrently modulate the osteogenic functions of mesenchymal stem cells and kill bacteria

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Journal of Materials Science & technology 2021年第14期73卷 31-44页

作者： Run Huang Lei Liu Bo Li Liang Qin Lei Huang Kelvin W.K.Yeung Yong Han School of Materials Science and Engineering Anhui University of Science and TechnologyHuainan232001China Department of orthopaedics and traumatology The University of Hong KongHong KongChina State-key laboratory for Mechanical Behavior of Materials Xi’an Jiaotong UniversityXi'an710049China Department of Gastrointestinal Surgery Hubei Cancer HospitalWuhan430060China shenzhen key laboratory for innovative technology in orthopaedic trauma The University of Hong Kong Shenzhen HospitalShenzhen518053China

Surface mechanical attrition treatment(SMAT)method is an effective way to generate nanograined(NG)surface on Ti-25 Nb-3 Mo-2 Sn-3 Zr(wt.%)(named as TLM),a kind ofβ-type titanium alloy,and the achieved nanocrystalline surface was proved to promote positive functions of osteoblastic *** this work,to further endow the NG TLM alloy with both good osteogenic and antibacterial properties,magnesium(Mg),silver(Ag)ion or both were introduced onto the NG TLM surface by ion implantation process,as a comparison,the Mg and Ag ions were also co-implanted onto coarsegrained(CG)TLM *** obtained results show that subsequent ion implantation does not remarkably induce the surface roughness and topography alteration of the SMAT-treated layers,and it also has little impact on the microstructure of the SMAT-derivedβ-Ti *** addition,the implanted Mg and Ag ions are observed to exist as MgO and metallic Ag na noparticles(NPs)embedding tightly in theβ-Ti matrix with grain size of about 15 and 7 nm,*** cell adhesion and functions(including proliferation,osteo-differentiation and extracellular matrix mineralization)of rabbit bone marrow mesenchymal stem cells(rBMMSCs)and the bacterial colonization of Staphylococcus aureus(***)on the different surfaces were *** in-vitro experimental results reveal that the Mg and Ag single-ion implanted NG surface either significantly promotes the rBMMSCs response or inhibits the growth ***,whereas the Mg/Ag coimplanted NG surface could concurrently enhance the rBMMSCs functions as well as inhibit the bacterial growth compared to the NG surface,and this efficacy is more pronounced as compared to the Mg/Ag co-implantation in the CG *** SMAT-achieved nanograins in the TLM surface layer are identified to not only play a leading role in determining the fate of rBMMSCs but also facilitate fabricating dualfunctio nal surface with both good osteogenic and antibacterial activities through co-imp

关键词： β-Type titanium Nanograined surface Ion implantation Stem cells Antibacterial property

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L-arginine loading porous PEEK promotes percutaneous tissue repairthrough macrophage orchestration

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Bioactive Materials 2024年第10期40卷 19-33页

作者： Tong Zhao Xingdan Liu Zhuangzhuang Chu Jing Zhao Dongya Jiang Xiaohua Dong Ziyi Lu Kelvin WKYeung Xuanyong Liu Liping Ouyang laboratory of key technology and Materials in Minimally Invasive Spine Surgery Tongren HospitalShanghai JiaoTong University School of MedicineChina Hongqiao International Institute of Medicine Tongren HospitalShanghai Jiao Tong University School of MedicineShanghai200336China State key laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of CeramicsChinese Academy of SciencesShanghai200050China School of Chemistry and Materials Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of Sciences1 Sub-lane XiangshanHangzhou310024China shenzhen key laboratory for innovative technology in orthopaedic Traum1 Guangdong Engineering TechnologyResearch Center for Orthopaedic Trauma RepairDepartment of Orthopaedics and TraumatologyThe University of Hong Kong Shenzhen HospitalShenzhenChina

Infection and poor tissue repair are the key causes of percutaneous implantation failure. However, there is a lackof effective strategies to cope with due to its high requirements of sterilization, soft tissue healing, andosseointegration. In this work, L-arginine (L-Arg) was loaded onto a sulfonated polyetheretherketone (PEEK)surface to solve this issue. Under the infection condition, nitric oxide (NO) and reactive oxygen species (ROS) areproduced through catalyzing L-Arg by inducible nitric oxide synthase (iNOS) and thus play a role in bacteriasterilization. Under the tissue repair condition, L-Arg is catalyzed to ornithine by Arginase-1 (Arg-1), whichpromotes the proliferation and collagen secretion of L929 and rBMSCs. Notably, L-Arg loading samples couldpolarize macrophages to M1 and M2 in infection and tissue repair conditions, respectively. The results in vivoshow that the L-Arg loading samples could enhance infected soft tissue sealing and bone regeneration. Insummary, L-Arg loading sulfonated PEEK could polarize macrophage through metabolic reprogramming,providing multi-functions of antibacterial abilities, soft tissue repair, and bone regeneration, which gives a newidea to design percutaneous implantation materials.

关键词： Polyetheretherketone Macrophage orchestration Sterilization Tissue repair

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Puerarin@Chitosan composite for infected bone repair through mimicking the bio-functions of antimicrobial peptides

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Bioactive Materials 2023年第3期21卷 520-530页

作者： Liping Ouyang Baohui Chen Xingdan Liu Donghui Wang Yang Li Yun Liao Kelvin W.K.Yeung Xuanyong Liu State key laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of CeramicsChinese Academy of SciencesShanghai200050China Hongqiao International Institute of edicine Shanghai Jiao Tong University School of MedicineShanghai200336China Cixi Center of Biomaterials Surface Engineering Ningbo315300China Department of Computational Biology for Individualised Medicine Centre for Individualised Infection Medicine(CiiM)&TWINCOREJoint Ventures Between the Helmholtz-Centre for Infection Research(HZI)and the Hannover Medical School(MHH)HannoverGermany shenzhen key laboratory for innovative technology in orthopaedic trauma Guangdong Engineering Technology Research Center for Orthopaedic Trauma RepairDepartment of Orthopaedics and TraumatologyThe University of Hong Kong Shenzhen HospitalShenzhenChina

It is important to eliminate lipopolysaccharide(LPS)along with killing bacteria in periprosthetic joint infection(PJI)therapy for promoting bone repair due to its effect to regulate macrophages *** natural antimicrobial peptides(AMPs)offer a good solution,the unknown toxicity,high cost and exogenetic immune response hamper their applications in *** this work,we fabricated a nanowire-like composite material,named P@C,by combining chitosan and puerarin via solid-phase reaction,which can finely mimic the bio-functions of ***,serving as the bacteria membrane puncture agent,and puerarin,serving as the LPS target agent,synergistically destroy the bacterial membrane structure and inhibit its recovery,thus endowing P@C with good antibacterial *** addition,P@C possesses good osteoimmunomodulation due to its ability of LPS elimination and macrophage differentiation *** in vivo results show that P@C can inhibit the LPS induced bone destruction in the Escherichia coli infected rat.P@C exhibits superior bone regeneration in Escherichia coli infected rat due to the comprehensive functions of its superior antibacterial property,and its ability of LPS elimination and immunomodulation.P@C can well mimic the functions of AMPs,which provides a novel and effective method for treating the PJI in clinic.

关键词： Osteoimmunomodulation Antibacterial Chitosan Puerarin Lipopolysaccharide

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Circular RNA circStag1 promotes bone regeneration by interacting with HuR

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Bone Research 2022年第3期10卷 565-577页

作者： Gaoyang Chen Canling Long Shang Wang Zhenmin Wang Xin Chen Wanze Tang Xiaoqin He Zhiteng Bao Baoyu Tan Jin Zhao Yongheng Xie Zhizhong Li Dazhi Yang Guozhi Xiao Songlin Peng Department of Spine Surgery and Institute for orthopaedic Research the Second Clinical Medical College of Jinan University(Shenzhen People’s Hospital)Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function RestorationShenzhen 518020China The First Affiliated Hospital Southern University of Science and TechnologyShenzhen 518055China The First Affiliated Hospital Jinan UniversityGuangzhou 510630China School of Medicine Southern University of Science and TechnologyGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease ResearchShenzhen Key Laboratory of Cell MicroenvironmentShenzhen 518055China

Postmenopausal osteoporosis is a common bone metabolic disorder characterized by deterioration of the bone microarchitecture,leading to an increased risk of ***,circular RNAs(circ RNAs)have been demonstrated to play pivotal roles in regulating bone ***,the underlying functions of circ RNAs in bone metabolism in postmenopausal osteoporosis remain ***,we report that circ Stag1 is a critical osteoporosis-related circ RNA that shows significantly downregulated expression in osteoporotic bone marrow mesenchymal stem cells(BMSCs)and clinical bone tissue samples from patients with *** of circ Stag1 significantly promoted the osteogenic capability of ***,we found that circ Stag1 interacts with human antigen R(Hu R),an RNA-binding protein,and promotes the translocation of Hu R into the cytoplasm.A high cytoplasmic level of Hu R led to the activation of the Wnt signaling pathway by stabilizing and enhancing low-density lipoprotein receptor-related protein 5/6(Lrp5/6)andβ-catenin expression,thereby stimulating the osteogenic differentiation of ***,overexpression of circ Stag1 in vivo by circ Stag1-loaded adeno-associated virus(circ Stag1-AAV)promoted new bone formation,thereby preventing bone loss in ovariectomized ***,we show that circ Stag1 plays a pivotal role in promoting the regeneration of bone tissue via Hu R/Wnt signaling,which may provide new strategies to prevent bone metabolic disorders such as postmenopausal osteoporosis.

关键词： metabolism thereby promoted

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Low-molecular-weight estrogenic phytoprotein suppresses osteoporosis development through positive modulation of skeletal estrogen receptors

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Bioactive Materials 2024年第12期42卷 299-315页

作者： John Akrofi Kubi Augustine Suurinobah Brah Kenneth Man Chee Cheung Andy Chun Hang Chen Yin Lau Lee Kai-Fai Lee Wei Qiao Yibin Feng Kelvin Wai Kwok Yeung Department of orthopaedics and traumatology Li Ka Shing Faculty of MedicineThe University of Hong Kong(HKU)PR China shenzhen key laboratory for innovative technology in orthopaedic trauma HKU-Shenzhen HospitalShenzhen518053PR China Department of Obstetrics and Gynaecology Li Ka Shing Faculty of MedicineHKU21 Sassoon RoadPR China shenzhen key laboratory of Fertility Regulation Reproductive Medicine CenterHKU-Shenzhen HospitalShenzhenPR China Applied Oral Sciences and Community Dental Care Faculty of DentistryPR China School of Chinese Medicine Li Ka Shing Faculty of MedicineThe University of Hong Kong(HKU)PR China

Age-related osteoporosis is a metabolic skeletal disorder caused by estrogen deficiency in postmenopausal *** use of anti-osteoporotic drugs such as bisphosphonates and FDA-approved anti-resorptive selective estrogen receptor modulators(SERMs)has been associated with various clinical *** recently discovered a low-molecular-weight biocompatible and osteoanabolic phytoprotein,called HKUOT-S2 protein(32 kDa),from Dioscorea opposita Thunb that can accelerate bone defect ***,we demonstrated that the HKUOT-S2 protein treatment can enhance osteoblasts-induced ossification and suppress osteoporosis development by upregulating skeletal estrogen receptors(ERs)ERα,ERβ,and GPR30 expressions in ***,HKUOT-S2 protein estrogenic activities promoted hMSCs-osteoblasts differentiation and functions by increasing osteogenic markers,ALP,and RUNX2 expressions,ALP activity,and osteoblast biomineralization in *** treatment impaired the HKUOT-S2 protein-induced ERs expressions,osteoblasts differentiation,and ***,we demonstrated that the HKUOT-S2 protein could bind to ERs to exert osteogenic and osteoanabolic *** results showed that the biocompatible HKUOT-S2 protein can exert estrogenic and osteoanabolic properties by positively modulating skeletal estrogen receptor signaling to promote ossification and suppress ***,there is no or limited data if any,on osteoanabolic *** HKUOT-S2 protein can be applied as a new osteoanabolic SERM for osteoporosis treatment.

关键词： Ovariectomy(ovx) Osteoporosis Osteoblast functions Estrogen receptors(ERs) HKUOT-S2 protein

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Hydrogel bioadhesives harnessing nanoscale phase separation for Achilles tendon repairing

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Nano Research 2024年第2期17卷 778-787页

作者： Jun Zhang Xingmei Chen Jingseng Lin Pei Zhang Iek Man Lei Yue Tao Jiajun Zhang Tian Luo Ji Liu Department of Mechanical and Energy Engineering Southern University of Science and TechnologyShenzhen 518055China Research and Innovation Center SKG Health TechnologyShenzhen 518000China SAFE(shenzhen)Medical technology Company Limited Shenzhen 518000China shenzhen key laboratory of Biomimetic Robotics and Intelligent Systems Department of Mechanical and Energy EngineeringSouthern University of Science and TechnologyShenzhen 518055China Guangdong Provincial key laboratory of Human-Augmentation and Rehabilitation Robotics in Universities Southern University of Science and TechnologyShenzhen 518055China

Repairing Achilles tendon has emerged as a long-standing challenge in the orthopaedic *** suture is the gold standard for re-attaching and repairing the fractured Achilles tendons in clinical surgeries,it is still subjected to numerous adverse side-effects,including chronic inflammatory,tendon tissue re-rupture,scar formation,and post-surgical peritendinous *** this work,we develop a class of hydrogel bioadhesives with tailored nanoscale phase separation for Achilles tendon *** address the existing limitations of sutures,our hydrogel bioadhesives encompass three core functionalities:(i)instant and tough adhesion to Achilles tendon tissues,(ii)extraordinary long-term adhesion robustness under wet and dynamic in vivo conditions,and(iii)anti-postsurgical peritendinous *** our hydrogel bioadhesives with sutures,such kind of integrated approach enables a conformable yet robust biointerface with the tendon tissues,and prevents the fibroblast migration and formation of connective tissues,thus facilitating the tendon *** hydrogel bioadhesives reported here open up new opportunities for the repairing of fractured Achilles tendons in diverse and complicated clinical scenarios.

关键词： hydrogels phase separation bioadhesion robustness tendon repairing

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Polydopamine-modified chitin conduits with sustained release of bioactive peptides enhance peripheral nerve regeneration in rats

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Neural Regeneration Research 2022年第11期17卷 2544-2550页

作者： Ci Li Song-Yang Liu Li-Ping Zhou Tian-Tian Min Meng Zhang Wei Pi Yong-Qiang Wen Pei-Xun Zhang Department of Orthopedics and trauma Peking University People’s HospitalBeijingChina key laboratory of trauma and Neural Regeneration Ministry of EducationBeijingChina National Center for trauma Medicine BeijingChina Beijing key laboratory for Bioengineering and Sensing technology School of Chemistry and Biological EngineeringUniversity of Science and Technology BeijingBeijingChina

The introduction of neurotrophic factors into injured peripheral nerve sites is beneficial to peripheral nerve ***,neurotrophic facto rs are rapidly degraded in vivo and obstruct axonal regeneration when used at a supraphysiological dose,which limits their clinical *** mimetic peptides have been developed to be used in place of neurotrophic factors because they have a similar mode of action to the original growth fa ctors and can activate the equivalent receptors but have simplified sequences and *** this study,we created polydopamine-modified chitin conduits loaded with brain-derived neurotrophic factor mimetic peptides and vascular endothelial growth fa ctor mimetic peptides(Chi/PDA-Ps).We found that the Chi/PDA-Ps conduits were less cytotoxic in vitro than chitin conduits alone and provided sustained release of functional *** this study,we evaluated the biocompatibility of the Chi/P DA-Ps ***-derived neurotrophic factor mimetic peptide and vascular endothelial growth fa ctor mimetic peptide synergistically promoted prolife ration of Schwann cells and secretion of neurotrophic factors by Schwann cells and attachment and migration of endothelial cells in *** Chi/P DA-Ps conduits were used to bridge a 2 mm gap between the nerve stumps in rat models of sciatic nerve *** found that the application of Chi/PDA-Ps conduits could improve the motor function of rats and reduce gastrocnemius *** electrophysiological results and the microstructure of regenerative nerves showed that the nerve conduction function and re myelination was further resto *** findings suggest that the Chi/PDA-Ps conduits have great potential in peripheral nerve injury repair.

关键词： angiogenesis bioactive peptides nerve repair neurotrophic factor peripheral nerve injury peripheral nerve regeneration polydopamine surface modification synergistic effects tissue engineering

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