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Journal of Materials Science & Technology 2023年第16期147卷 132-144页

作者： Yufeng Zheng Xiao Liu Danni Shen Wenting Li Yan Cheng Ming Yang Yuhui Kou Baoguo Jiang Academy for Advanced Interdisciplinary Studies Peking UniversityBeijing 100871China School of Materials Science and Engineering Peking UniversityBeijing 100871China International Research Organization for Advanced Science and Technology(IROAST) Kumamoto UniversityKumamoto 860-8555Japan Department of Orthopaedics and Traumatology Peking University People’s HospitalBeijing 100044China Key Laboratory of Trauma and Neural Regeneration(Peking University) Ministry of EducationBeijing 100044China National Center for Trauma Medicine Beijing 100044China

The implants made of metallic biomaterials help healing the bone fracture but also affect the bone repair process.As proposed in Matter 4(2021)2548–2650 by Wang et al.,a precisely adaptable biomaterial ought to recapitulate the targeted tissue with spatiotemporal precision and hierarchical accuracy,ranging from atoms and molecules(genes,proteins,etc.)to cells(including organelles)and to tissues and organs.In comparison to traditional bio-inert metallic bone implants such as Co-based alloys and Ti alloys,biodegradable metal(Mg and Zn alloys)bone implants had been developed and might arise many unexpected variables in the bone repair,due to their bioactive nature.In this paper,the bone repair without and with the presence of metallic implants is compared.Thereafter,the perspectives concerning the interactions between the bone tissues and biodegradable metal implants are put forward,and how to better mimic in vivo biodegradation by in vitro experiments is proposed for further research and development of biodegradable metals.

关键词： Biodegradable metals Magnesium Zinc bone healing Precise bioadaptability

Effect of non-steroidal anti-inflammatory drugs on fracture healing in children:A systematic review

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World Journal of Orthopedics 2022年第5期13卷 494-502页

作者： Sarah Stroud Toshali Katyal Alex L Gornitzky Ishaan Swarup Department of Orthopaedic Surgery University of CaliforniaSan FranciscoCA 94143United States Department of Orthopaedic Surgery University of CaliforniaSan Francisco Benioff Children’s HospitalCA 94143United States Department of Orthopaedic Surgery University of CaliforniaSan Francisco Benioff Children’s Hospital OaklandOaklandCA 94609United States

BACKGROUND Non-steroidal anti-inflammatory drugs(NSAIDs)are among the most commonly prescribed medications in the United States.Although they are safe and effective means of analgesia for children with broken bones,there is considerable variation in their clinical use due to persistent concerns about their potentially adverse effect on fracture healing.AIM To assess whether NSAID exposure is a risk factor for fracture nonunion in children.METHODS We systematically reviewed the literature reporting the effect of NSAIDs on bone healing.We included all clinical studies that reported on adverse bone healing complications in children with respect to NSAID exposure.The outcomes of interest were delayed union or nonunion.Study quality was assessed using the Newcastle-Ottawa scale for non-randomized studies.A final table was constructed summarizing the available evidence.RESULTS A total of 120 articles were identified and screened,of which 6 articles were included for final review.Nonunion in children is extremely rare;among the studies included,there were 2011 nonunions among 238822 fractures(0.84%).None of the included studies documented an increased risk of nonunion or delayed bone healing in those children who are treated with NSAIDs in the immediate post-injury or peri-operative time period.Additionally,children are likely to take these medications for only a few days after injury or surgery,further decreasing their risk of adverse side-effects.CONCLUSION This systematic review suggests that NSAIDS can be safely prescribed to pediatric orthopaedic patients absent other contraindications without concern for increased risk of fracture non-union or delayed bone healing.Additional prospective studies are needed focusing on higher risk fractures and elective orthopaedic procedures such as osteotomies and spinal fusion.

关键词： Non-steroidal anti-inflammatory drug Nonunion Complication Pediatric fractures Pain management bone healing

In vitro and in vivo study on fine-grained Mg-Zn-RE-Zr alloy as a biodegradeable orthopedic implant produced by friction stir processing

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Bioactive Materials 2023年第10期28卷 448-466页

作者： Vasanth C.Shunmugasamy Marwa AbdelGawad Muhammad Umar Sohail Talal Ibrahim Talha Khan Thomas Daniel Seers Bilal Mansoor Mechanical Engineering Program Texas A&M University at QatarEducation CityDohaQatar Department of Mechanical Engineering Texas A&M University3123 TAMUCollege StationTX 77843USA Proteomics Core Weill Cornell MedicineEducation CityDohaQatar Department of Surgery Division of Orthopedic SurgerySidra MedicineDohaQatar Clinical Orthopedic Surgery Weill Cornell MedicineEducation CityDohaQatar Petroleum Engineering Program Texas A&M University at QatarEducation CityDohaQatar Department of Materials Science and Engineering Texas A&M University3003 TAMUCollege StationTX 77843USA

Magnesium alloys containing biocompatible components show tremendous promise for applications as temporary biomedical devices. However, to ensure their safe use as biodegradeable implants, it is essential to control their corrosion rates. In concentrated Mg alloys, a microgalvanic coupling between the α-Mg matrix and secondary precipitates exists which results in increased corrosion rate. To address this challenge, we engineered the microstructure of a biodegradable Mg-Zn-RE-Zr alloy by friction stir processing (FSP), improving its corrosion resistance and mechanical properties simultaneously. The FS processed alloy with refined grains and broken and uniformly distributed secondary precipitates showed a relatively uniform corrosion morphology accompanied with the formation of a stable passive layer on the alloy surface. In vivo corrosion evaluation of the processed alloy in a small animal model showed that the material was well-tolerated with no signs of inflammation or harmful by-products. Remarkably, the processed alloy supported bone until it healed till eight weeks with a low in vivo corrosion rate of 0.7 mm/year. Moreover, we analyzed blood and histology of the critical organs such as liver and kidney, which showed normal functionality and consistent ion and enzyme levels, throughout the 12- week study period. These results demonstrate that the processed Mg-Zn-RE-Zr alloy offers promising potential for osseointegration in bone tissue healing while also exhibiting controlled biodegradability due to its engineered microstructure. The results from the present study will have profound benefit for bone fracture management, particularly in pediatric and elderly patients.

关键词： Biodegradable magnesium bone healing Friction stir processing Microstructure Corrosion resistance

Dynamic degradation patterns of porous polycaprolactone/β-tricalcium phosphate composites orchestrate macrophage responses and immunoregulatory bone regeneration

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Bioactive Materials 2023年第3期21卷 595-611页

作者： Hao Wu Xinghui Wei Yichao Liu Hui Dong Zhen Tang Ning Wang Shusen Bao Zhigang Wu Lei Shi Xiongfei Zheng Xiaokang Li Zheng Guo Department of Orthopaedics Tangdu HospitalFourth Military Medical UniversityXi’anShaanxi710038PR China Department of Orthopaedics Xijing HospitalFourth Military Medical UniversityXi’anShaanxi710032PR China Department of Orthopaedics The 63750 Hospital of People’s Liberation ArmyXi’anShaanxi710038PR China State Key Laboratory of Robotics Shenyang Institute of AutomationChinese Academy of SciencesShenyangLiaoning110000PR China

Biodegradable polycaprolactone/β-tricalcium phosphate(PT)composites are desirable candidates for bone tissue engineering applications.A higherβ-tricalcium phosphate(TCP)ceramic content improves the mechanical,hydrophilic and osteogenic properties of PT scaffolds in vitro.Using a dynamic degradation reactor,we estab-lished a steady in vitro degradation model to investigate the changes in the physio-chemical and biological properties of PT scaffolds during degradation.PT46 and PT37 scaffolds underwent degradation more rapidly than PT scaffolds with lower TCP contents.In vivo studies revealed the rapid degradation of PT(PT46 and PT37)scaffolds disturbed macrophage responses and lead to bone healing failure.Macrophage co-culture assays and a subcutaneous implantation model indicated that the scaffold degradation process dynamically affected macro-phage responses,especially polarization.RNA-Seq analysis indicated phagocytosis of the degradation products of PT37 scaffolds induces oxidative stress and inflammatory M1 polarization in macrophages.Overall,this study reveals that the dynamic patterns of biodegradation of degradable bone scaffolds highly orchestrate immune responses and thus determine the success of bone regeneration.Therefore,through evaluation of the biological effects of biomaterials during the entire process of degradation on immune responses and bone regeneration are necessary in order to develop more promising biomaterials for bone regeneration.

关键词： Polycaprolactone/β-TCP Dynamic degradation Macrophage response bone healing

Biodegradable magnesium barrier membrane used for guided bone regeneration in dental surgery

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Bioactive Materials 2022年第8期7卷 152-168页

作者： Patrick Rider Zeljka Peric Kacarevic Akiva Elad Drazen Tadic Daniel Rothamel Gerrit Sauer Fabien Bornert Peter Windisch David Botond Hangyasi Balint Molnar Emely Bortel Bernhard Hesse Frank Witte Department of Prosthodontics Geriatric Dentistry and Craniomandibular DisordersCharite-Universitatsmedizin BerlinAßmannshauser Straße 4-614197BerlinGermany Botiss Biomaterials AG Ullsteinstrasse 10812109BerlinGermany Department of Anatomy Histology EmbryologyPathology Anatomy and Pathology HistologyFaculty of Dental Medicine and HealthUniversity of OsijekOsijek31000Croatia CMF Surgery Johannes BLA HospitalMonchengladbachGermany Dental Clinic University of StrasbourgFrance Department of Periodontology Semmelweis UniversityBudapestHungary Xploraytion GmbH Bismarkstrasse 11BerlinGermany Biotrics Bioimplants AG Ullsteinstrasse 10812109BerlinGermany

Barrier membranes are commonly used as part of the dental surgical technique guided bone regeneration(GBR)and are often made of resorbable collagen or non-resorbable materials such as PTFE.While collagen membranes do not provide sufficient mechanical protection of the covered bone defect,titanium reinforced membranes and non-resorbable membranes need to be removed in a second surgery.Thus,biodegradable GBR membranes made of pure magnesium might be an alternative.In this study a biodegradable pure magnesium(99.95%)membrane has been proven to have all of the necessary requirements for an optimal regenerative outcome from both a mechanical and biological perspective.After implantation,the magnesium membrane separates the regenerating bone from the overlying,faster proliferating soft tissue.During the initial healing period,the membrane maintained a barrier function and space provision,whilst retaining the positioning of the bone graft material within the defect space.As the magnesium metal corroded,it formed a salty corrosion layer and local gas cavities,both of which extended the functional lifespan of the membrane barrier capabilities.During the resorption of the magnesium metal and magnesium salts,it was observed that the membrane became surrounded and then replaced by new bone.After the membrane had completely resorbed,only healthy tissue remained.The in vivo performance study demonstrated that the magnesium membrane has a comparable healing response and tissue regeneration to that of a resorbable collagen membrane.Overall,the magnesium membrane demonstrated all of the ideal qualities for a barrier membrane used in GBR treatment.

关键词： Magnesium Biodegradable Implant GBR bone healing Soft tissue healing

Application of a new anatomic hook-rod-pedicle screw system in young patients with lumbar spondylolysis:A pilot study

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World Journal of Clinical Cases 2022年第17期10卷 5680-5689页

作者： Duan-Ming Li Yong-Chao Li Wei Jiang Bao-Gan Peng Department of Orthopaedics The Third Medical Center of PLA General HospitalBeijing 100039China Department of Anesthesiology The Third Medical Center of PLA General HospitalBeijing 100039China

BACKGROUND The pedicle screw-laminar hook system has strong fixation and is conducive to bone graft fusion for lumbar spondylolysis.However,the current pedicle screwlaminar hook fixation system is not specifically designed for lumbar spondylolysis.AIM To investigate the clinical effects of a new anatomical hook-rod-pedicle screw system in the treatment of lumbar spondylolysis in young adults.METHODS We designed a new anatomic hook-rod-pedicle screw system for young patients with lumbar spondylolysis.The isthmus and the corresponding pedicle screw entry point were exposed through the intermuscular approach.Autogenous iliac bone graft was obtained to bridge the isthmus defect,and then the anatomic hook-rod-pedicle screw system was used to fix the isthmus in 15 young patients.RESULTS At 24 mo follow-up,the visual analogue scale score of low back pain decreased from 6.73±0.88 to 0.73±0.59,and the Oswestry disability index score decreased from 58.20±8.99 to 7.87±4.97.Computed tomography showed bilateral isthmic bone healing in 14 cases and unilateral isthmic bone healing in 1 case.Magnetic resonance imaging showed that the lumbar disc signal of diseased segment and adjacent segments had no change compared with that before surgery.The pain visual analogue scale score of the donor site was 0.20±0.41 at the last follow-up.According to the Modified Macnab score,the excellent and good rate was 100%.CONCLUSION The application of this new anatomical hook-rod-pedicle screw system to treat young patients with lumbar spondylolysis has the advantages of less trauma,a simple operation and satisfactory clinical effects.

关键词： Lumbar spondylolysis Hook-rod-pedicle screw system Internal fixation bone healing

Biodegradable magnesium fixation screw for barrier membranes used in guided bone regeneration

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Bioactive Materials 2022年第8期7卷 15-30页

作者： Zeljka Peric Kacarevic Patrick Rider Akiva Elad Drazen Tadic Daniel Rothamel Gerrit Sauer Fabien Bornert Peter Windisch David Botond Hangyasi Balint Molnar Till Kammerer Bernhard Hesse Emely Bortel Marco Bartosch Frank Witte Department of Anatomy Histology EmbryologyPathology Anatomy and Pathology HistologyFaculty of Dental Medicine and HealthUniversity of OsijekOsijek31000Croatia Department of Prosthodontics Geriatric Dentistry and Craniomandibular DisordersCharite-Universitatsmedizin BerlinAßmannshauser Straße 4–614197BerlinGermany Botiss Biomaterials AG Ullsteinstrasse 10812109BerlinGermany CMF Surgery Johannes BLA HospitalMonchengladbachGermany Dental Clinic University of StrasbourgFrance Department of Periodontology Semmelweis UniversityBudapestHungary Xploraytion GmbH Bismarkstrasse 11BerlinGermany University Hospital Munich Department of Dermatology and AllergyFrauenlobstr.9-1180337MunichGermany Biotrics Bioimplants AG Ullsteinstrasse 10812109BerlinGermany

An ideal fixation system for guided bone(GBR)regeneration in oral surgery must fulfil several criteria that includes the provision of adequate mechanical fixation,complete resorption when no longer needed,complete replacement by bone,as well as be biocompatible and have a good clinical manageability.For the first time,a biodegradable magnesium fixation screw made of the magnesium alloy WZM211 with a MgF2 coating has been designed and tested to fulfill these criteria.Adequate mechanical fixation was shown for the magnesium fixation screw in several benchtop tests that directly compared the magnesium fixation screw with an equivalent polymeric resorbable device.Results demonstrated slightly superior mechanical properties of the magnesium device in comparison to the polymeric device even after 4 weeks of degradation.Biocompatibility of the magnesium fixation screw was demonstrated in several in vitro and in vivo tests.Degradation of the magnesium screw was investigated in in vitro and in vivo tests,where it was found that the screw is resorbed slowly and completely after 52 weeks,providing adequate fixation in the early critical healing phase.Overall,the magnesium fixation screw demonstrates all of the key properties required for an ideal fixation screw of membranes used in guided bone regeneration(GBR)surgeries.

关键词： Magnesium Biodegradable Implant GBR bone healing Soft tissue healing

Application of osteoinductive calcium phosphate ceramics in children’s endoscopic neurosurgery:report of five cases

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Regenerative Biomaterials 2018年第4期5卷 221-227页

作者： Jia Wei Hufei Qian Yu Liu Jiangang Liu Rui Zhao Xiao Yang Xiangdong Zhu Ruoping Chen Xingdong Zhang Department of Neurosurgery Shanghai Children’s HospitalShanghai Jiao Tong UniversityShanghai 200060China National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610064China

This work aimed at investigating the possibility and effectiveness of osteoinductive calcium phosphate(CaP)ceramics to close the drilled skull holes and prevent the postoperative cerebrospinal fluid(CSF)leaking in children’s endoscopic neurosurgery.Five children patients(four boys and one girl,3-to 8-years old)underwent the surgery,in which the endoscopic third ventriculostomy(ETV)was operated in four cases of hydrocephalus,and biopsy and ETV were both performed in one case of pineal tumor.The drilled skull holes were filled with the commercial osteoinductive CaP ceramics.The patients were followed up by CT scan at 1,7 days,3 and 6 months postoperatively.All the five cases were successful,and the holes were closed well after filled with the ceramics.The follow-up survey showed that no CSF leaking or rejection reaction was found.The CT scan indicated that the drilled holes began healing at 7 days postoperatively,and a relatively complete healing happened at 6 months postoperatively.The excellent ability of the CaP ceramics to induce bone regeneration was also confirmed by repairing the skull defects in a monkey model.The results of μ-CT and histological analysis showed that a bony structure with irregular array occurred at the defect area,and the newly formed bone volume density reached 65.7%.In conclusion,the osteoinductive CaP ceramics could be an ideal material to treat the drilled skull holes in children’s endoscopic neurosurgery and prevent CSF leaking afterwards.However,further investigation with more cases and longer follow-up was required to evaluate the clinical effect.

关键词： neuroendoscopy skull holes CSF leaking osteoinductive CaP ceramics bone healing

Advancing application of mesenchymal stem cell-based bone tissue regeneration

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Bioactive Materials 2021年第3期6卷 666-683页

作者： Fengqing Shang Yang Yu Shiyu Liu Leiguo Ming Yongjie Zhang Zhifei Zhou Jiayu Zhao Yan Jin State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi Key Laboratory of Oral DiseasesCenter for Tissue EngineeringFourth Military Medical UniversityXi'anShaanxi710032China Department of Stomatology The 306th Hospital of PLABeijing100101China Department of Periodontology School and Hospital of StomatologyCheeloo College of MedicineShandong University&Shandong Key Laboratory of Oral Tissue Regeneration&Shandong Engineering Laboratory for Dental Materials and Oral Tissue RegenerationJinanShandong250012China Department of Stomatology General Hospital of Tibetan Military CommandLhasa850000China Bureau of Service for Veteran Cadres of PLA in Beijing Beijing100001China

Reconstruction of bone defects,especially the critical-sized defects,with mechanical integrity to the skeleton is important for a patient's rehabilitation,however,it still remains challenge.Utilizing biomaterials of human origin bone tissue for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural bone tissue with regard to its properties.However,not only efficacious and safe but also costeffective and convenient are important for regenerative biomaterials to achieve clinical translation and commercial success.Advances in our understanding of regenerative biomaterials and their roles in new bone formation potentially opened a new frontier in the fast-growing field of regenerative medicine.Taking inspiration from the role and multicomponent construction of native extracellular matrix(ECM)for cell accommodation,the ECM-mimicking biomaterials and the naturally decellularized ECM scaffolds were used to create new tissues for bone restoration.On the other hand,with the going deep in understanding of mesenchymal stem cells(MSCs),they have shown great promise to jumpstart and facilitate bone healing even in diseased microenvironments with pharmacology-based endogenous MSCs rescue/mobilization,systemic/local infusion of MSCs for cytotherapy,biomaterials-based approaches,cell-sheets/-aggregates technology and usage of subcellular vesicles of MSCs to achieve scaffolds-free or cell-free delivery system,all of them have been shown can improve MSCsmediated regeneration in preclinical studies and several clinical trials.Here,following an overview discussed autogenous/allogenic and ECM-based bone biomaterials for reconstructive surgery and applications of MSCsmediated bone healing and tissue engineering to further offer principles and effective strategies to optimize MSCs-based bone regeneration.

关键词： Mesenchymal stem cells bone healing Regenerative medicine Biomaterials Extracellular matrix Cytotherapy Cell-sheets/-aggregates Exosomes