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Prevention strategies of postoperative adhesion in soft tissues by applying biomaterials:Based on the mechanisms of occurrence and development of adhesions

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Bioactive Materials 2023年第8期26卷 387-412页

作者： Jie Liao Xiaoming Li Yubo Fan Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education Beijing Advanced Innovation Center for Biomedical EngineeringSchool of Biological Science and Medical EngineeringBeihang UniversityBeijing100083China

Postoperative adhesion(POA)widely occurs in soft tissues and usually leads to chronic pain,dysfunction of adjacent organs and some acute complications,seriously reducing patients’quality of life and even being life-threatening.Except for adhesiolysis,there are few effective methods to release existing adhesion.However,it requires a second operation and inpatient care and usually triggers recurrent adhesion in a great incidence.Hence,preventing POA formation has been regarded as the most effective clinical strategy.Biomaterials have attracted great attention in preventing POA because they can act as both barriers and drug carriers.Nevertheless,even though much reported research has been demonstrated their efficacy on POA inhibition to a certain extent,thoroughly preventing POA formation is still challenging.Meanwhile,most biomaterials for POA prevention were designed based on limited experiences,not a solid theoretical basis,showing blindness.Hence,we aimed to provide guidance for designing anti-adhesion materials applied in different soft tissues based on the mechanisms of POA occurrence and development.We first classified the postoperative adhesions into four categories according to the different components of diverse adhesion tissues,and named them as“membranous adhesion”,“vascular adhesion”,“adhesive adhesion”and“scarred adhesion”,respectively.Then,the process of the occurrence and development of POA were analyzed,and the main influencing factors in different stages were clarified.Further,we proposed seven strategies for POA prevention by using biomaterials according to these influencing factors.Meanwhile,the relevant practices were summarized according to the corresponding strategies and the future perspectives were analyzed.

关键词： Prevention of postoperative adhesions(POA) Soft tissues Mechanisms of occurrence and development Biomaterials

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Multi-functionalized nanofibers with reactive oxygen species scavenging capability and fibrocartilage inductivity for tendon-bone integration

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Journal of Materials Science & Technology 2021年第11期70卷 91-104页

作者： Peixing Chen Sixiang Wang Zhi Huang Yan Gao Yu Zhang Chunli Wang Tingting Xia Linhao Li Wanqian Liu Li Yang key laboratory of Biorheological Science and Technology Ministry of EducationBioengineering CollegeChongqing UniversityChongqing400044China Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education School of Biological Science and Medical EngineeringBeihang UniversityBeijing100083China

The presence of excessive reactive oxygen species(ROS)after injuries to the enthesis could lead to cellular oxidative damage,high inflammatory response,chronic inflammation,and limited fibrochondral inductivity,making tissue repair and functional recovery difficult.Here,a multifunctional silk fibroin nanofiber modified with polydopamine and kartogenin was designed and fabricated to not only effectively reduce inflammation by scavenging ROS in the early stage of the enthesis healing but also enhance fibrocartilage formation with fibrochondrogenic induction in the later stages.The in vitro results confirmed the antioxidant capability and the fibrochondral inductivity of the functionalized nanofibers.In vivo studies showed that the multifunctional nanofiber can significantly improve the integration of tendon-bone and accelerate the regeneration of interface tissue,resulting in an excellent biomechanical property.Thus,the incorporation of antioxidant and bio-active molecules into extracellular matrix-like biomaterials in interface tissue engineering provides an integrative approach that facilitates damaged tissue regeneration and functional recovery,thereby improving the clinical outcome of the engineered tissue.

关键词： Polydopamine Kartogenin Tendon-bone interface Reactive oxygen species Scavenging Fibrochondrogenic

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Effect of mechanical stresses on degradation behavior of high-purity magnesium in bone environments

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Journal of Materials Science & Technology 2024年第4期171卷 252-261页

作者： Yan Yao Jie Xia Lizhen Wang Yuanming Gao Xili Ding Chao Wang Yubo Fan key laboratory of biomechanics and mechanobiology(Beihang University) Ministry of EducationBeijing Advanced Innovation Center for Biomedical EngineeringSchool of Biological Science and Medical EngineeringSchool of Engineering MedicineBeihang UniversityBeijing 100083China

High-purity(HP)magnesium(Mg)has emerged as a promising biomaterial for supporting functional bone tissue.Our previous study found that mechanical stresses and the surrounding fibrotic tissue(subcuta-neous)both play crucial roles in the degradation of HP Mg.However,due to challenges in the degradation and regeneration process in vivo,it remains unclear how stress affects HP Mg degradation in bone en-vironments,limiting its further application.In this study,novel loading devices were designed and the effects of tensile and compressive stresses on HP Mg degradation in vivo and in vitro bone environments were quantitatively analyzed.In addition,bone osteointegration around HP Mg was explored preliminar-ily.Tensile stress increases the degradation rate of HP Mg in vivo and in vitro.HP Mg degradation in vivo is more sensitive to stress factors than in vitro,but the sensitivity decreases with corrosion time.The volume loss rate of HP Mg is multilinear with the applied stress and degradation time.The volume of bone tissue surrounding HP Mg is larger in the no-stress group compared to the stressed groups,which is more pronounced with increasing implantation time.These results provide valuable insights for optimiz-ing the design of HP Mg-based implants considering load conditions.This will help to achieve a balance between the degradation rate of the implant and the regeneration rate of the surrounding bone.

关键词： High-purity magnesium Quantitative stresses Degradation Bone environments In vivo and in vitro

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Synthesis and Characterization of Chitosan-graft-Poly(lactic acid) Copolymer

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Chinese Journal of Polymer Science 2014年第1期32卷 43-50页

作者：牛旭锋 Feng Tian Li-zhen Wang Xiao-ming Li Gang Zhou 樊瑜波 Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education School of Biological Science and Medical Engineering Beihang University BUAA Research Institute

Chitosan-graft-poly（lactic acid）（CS-g-PLA） copolymer was synthesized through emulsion self-assembly in a water-in-oil （W/O） microemulsion. The water phase was composed of CS aqueous solution, while the oil phase was made up of PLA in chloroform. The W/O microemulsion was fabricated in the presence of surfactant span-80 and the self-assembly was performed between PLA and CS under the effect of N-（3-dimethylaminopropyl）-N＇ethylcarbodiimide hydrochloride （EDC＇HCI）. FTIR and IH-NMR analysis indicated PLA was grafted onto the backbone of CS via the reaction between the carboxyl groups in PLA and the amino groups in CS. 1H-NMR characterization further revealed the grafting content of PLA was 16%. The obtained CS-g-PLA could self-assemble to form micelles, their size distributed in the range of 125-375 nm with average diameter of 142 nm. The present design integrates the favorable biological properties of CS and the excellent mechanical properties of PLA, which makes CS-g-PLA copolymer a promising candidate as a carrier for targeted bioactive molecules delivery.

关键词： Poly（lactic acid） Chitosan Copolymer Self-assembling Grafting.

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Fatigue behavior of cortical bone:a review

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Acta Mechanica Sinica 2021年第3期37卷 516-526,I0004页

作者： Jingwen Li He Gong Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education Beijing Advanced Innovation Center for Biomedical EngineeringSchool of Biological Science and Medical EngineeringBeihang UniversityBeijing 100191China

Fatigue is a common cause of bone failure.As the main load-bearing tissue,cortical bone carries a considerable share of load in the whole bone.Under cyclic loading condition,microdamage may generates and accumulates in cortical bone,which further triggers the fracture of bone.It is crucial to explore the fatigue properties of cortical bone and the influential factors for both clinical diagnosis and establishment of models that can predict fatigue failure of human cortical bone.In this review,the fatigue behavior of cortical bone was investigated.Through the complex hierarchical structure and self-repairing process,the risk of catastrophic fracture is reduced.Based on these understandings,the multiple influential factors of cortical bone fatigue properties were analyzed,which were considered to be a combination of internal and external factors.The internal factors include material properties of bone composition(i.e.,mineral,organic material,and water)and bone structure.External factors refer to loading condition such as frequency,amplitude and direction of load.Besides,age,disease,radiation exposure and other factors affect the fatigue behavior of bone by altering one or more factors mentioned above.

关键词： Cortical bone Fatigue Microdamage Influential factor

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A surface-eroding poly(1,3-trimethylene carbonate)coating for magnesium based cardiovascular stents with stable drug release and improved corrosion resistance

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Bioactive Materials 2022年第1期7卷 144-153页

作者： Hongyan Tang Shuangshuang Li Yuan Zhao Cunli Liu Xuenan Gu Yubo Fan Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education School of Biological Science and Medical EngineeringBeihang UniversityBeijing10083China Beijing Advanced Innovation Centre for Biomedical Engineering Beihang UniversityBeijing102402China

Magnesium alloys with integration of degradability and good mechanical performance are desired for vascular stent application.Drug-eluting coatings may optimize the corrosion profiles of magnesium substrate and reduce the incidence of restenosis simultaneously.In this paper,poly(trimethylene carbonate)(PTMC)with different molecular weight(50,000 g/mol named as PTMC5 and 350,000 g/mol named as PTMC35)was applied as drug-eluting coatings on magnesium alloys.A conventional antiproliferative drug,paclitaxel(PTX),was incorporated in the PTMC coating.The adhesive strength,corrosion behavior,drug release and biocompatibility were investigated.Compared with the PLGA control group,PTMC coating was uniform and gradually degraded from surface to inside,which could provide long-term protection for the magnesium substrate.PTMC35 coated samples exhibited much slower corrosion rate 0.05μA/cm^(2)in comparison with 0.11μA/cm^(2)and 0.13μA/cm^(2)for PLGA and PTMC5 coated counterparts.In addition,PTMC35 coating showed more stable and sustained drug release ability and effectively inhibited the proliferation of human umbilical vein vascular smooth muscle cells.Hemocompatibility test indicated that few platelets were adhered on PTMC5 and PTMC35 coatings.PTMC35 coating,exhibiting surface erosion behavior,stable drug release and good biocompatibility,could be a good candidate as a drug-eluting coating for magnesium-based stent.

关键词： Magnesium alloy Polymeric coating Surface erosion Drug release Cardiovascular stents

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Fabrication and biological evaluation of polyether ether ketone(PEEK)/bioceramic composites

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Progress in Natural Science:Materials International 2022年第3期32卷 334-339页

作者： Junfeng Chen Guangxiu Cao Ying Li Ning Li Zhipo Du Xiaoming Li Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education Beijing Advanced Innovation Center for Biomedical Engineering School of Biological Science and Medical Engineering Beihang University Department of Orthopedics The Fourth Central Hospital of Baoding City

The repair of vascularized bone defects represents a significantly clinical challenge, and vascular regeneration is one of the necessary factors to promote bone tissue regeneration. To effectively repair large bone defects, new bone tissue must regenerate with a rich vascular network. Therefore, the development of biomaterials that can promote the regeneration of vascularized bone tissue is currently receiving attention from researchers. In this study, Li–Ca–Si bioceramics(LCS) containing Li, Ca, and Si elements was developed, then LCS was compounded with PEEK to prepare PEEK+10% LCS, PEEK+20% LCS, PEEK+30% LCS, and the effect of LCS-PEEK composite biomaterials on the proliferation and angiogenic ability of human umbilical vascular endothelial cells(HUVECs)further explored by Cell Counting Kit-8(CCK-8), scanning electron microscope(SEM), quantitative real-time PCR(QPCR), Western Blotting and enzyme linked immunosorbent assay(ELISA). The results showed that HUVECs inoculated on 30%LCS + PEEK material exhibited the best proliferation ability. And the adhesion ability of endothelial cells on PEEK gradually increased with the increase of LCS contents. Furthermore, the angiogenic ability of HUVECs on LCS-PEEK composites was examined using QPCR and Western blotting, and the results showed that the expression of angiogenic-related genes and proteins of HUVECs on PEEK composites gradually increased with increasing LCS concentration. These results demonstrated that the angiogenic ability of HUVECs was effectively stimulated by LCS-modified PEEK materials. The present results indicate that the PEEK material can be modified with bioceramics to promote angiogenesis, and this study lay the foundation for the subsequent development of scaffolds that promote vascularized bone tissue regeneration.

关键词： Polyether ether ketone(PEEK) Li–Ca–Si bioceramics (LCS) Human umbilical vascular endothelial cells (HUVECs) Angiogenesis Bone tissue engineering

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Biological analysis of woodpecker’s brain after impact experiments

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Science China(Technological Sciences) 2021年第5期64卷 1101-1106页

作者： XU Peng NI YiKun LIU JingLong ZHANG WeiRong LIU SiJian WANG LiZhen FAN YuBo Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education Beijing Advanced Innovation Centre for Biomedical EngineeringSchool of Biological Science and Medical EngineeringBeihang UniversityBeijing 100083China

Woodpeckers can withstand a fierce impact during pecking.Previous studies have focused on the biomechanical analysis of the pecking process,the properties of the beak and hyoid bone of woodpecker;however,the biological characteristics of the woodpecker brain are also important in resisting impact injuries.We employed impact experiments and biological analysis in normal and injured brains to reveal the impact-resistant biological characteristics of woodpecker brains,as well as the impact energy’s biological effects on the woodpecker brain.The hoopoe,which has a similar size but only a slight pecking behavior,was selected as the control group to compare brain morphology and neuronal cells differences in normal brains between woodpecker and hoopoe by sectioning and staining.A loading device was designed to conduct a quantifiable impact energy to the woodpeckers’head.Four groups of woodpeckers were impacted with the same energy on the forehead,beak,tempus and occiput,respectively.Biological changes in the injured brains were evaluated by Nissl staining and enzyme-linked immunosorbent assay.The results showed that:(1)woodpeckers had a larger cerebellum and a higher density of Nissl bodies than hoopoe;(2)Nissl apoptosis appeared in the brain samples after the forehead and the occiput impact experiments,but no obvious Nissl body apoptosis was observed after impact on the tempus and the beak;(3)β-amyloid protein accumulated in the normal status woodpecker brain.This study reveals that:woodpecker brain morphology is well-adapted to impact,woodpecker heads display location-dependent protective performance,with beak and tempus regions having a better protective performance than the forehead and occiput,Nissl apoptosis appears in injured woodpecker brains,and that the accumulation ofβ-amyloid protein does not show a direct relationship with the injury state of woodpecker’s brain tissue in our study.

关键词： woodpecker biomechanics impact experiments impact resistance biological analysis

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Magnesium based degradable biomaterials： A review

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Frontiers of Materials Science 2014年第3期8卷 200-218页

作者： Xue-Nan GU Shuang-Shuang LI Xiao-Ming LI Yu-Bo FAN Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education School of Biological Science and Medical Engineering Beihang University Beijing 100191 China

Magnesium has been suggested as a revolutionary biodegradable metal for biomedical applications. The corrosion of magnesium, however, is too rapid to match the rates of tissue healing and, additionally, exhibits the localized corrosion mechanism. Thus it is necessary to control the corrosion behaviors of magnesium for their practical use. This paper comprehensively reviews the research progress on the development of representative magnesium based alloys, including Mg-Ca, Mg-Sr, Mg-Zn and Mg-REE alloy systems as well as the bulk metallic glass. The influence of alloying element on their microstructures, mechanical properties and corrosion behaviors is summarized. The mechanical and corrosion properties of wrought magnesium alloys are also discussed in comparison with those of cast alloys. Furthermore, this review also covers research carried out in the field of the degradable coatings on magnesium alloys for biomedical applications. Calcium phosphate and biodegradable polymer coatings are discussed based on different preparation techniques used. We also compare the effect of different coatings on the corrosion behaviors of magnesium alloys substrate.

关键词： magnesium alloy degradable biomaterial coating degradation corrosion

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Integrated gradient tissue-engineered osteochondral scaffolds:Challenges,current efforts and future perspectives

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Bioactive Materials 2023年第2期20卷 574-597页

作者： Xiaolian Niu Ning Li Zhipo Du Xiaoming Li Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education Beijing Advanced Innovation Center for Biomedical EngineeringSchool of Biological Science and Medical EngineeringBeihang UniversityBeijing100083China Department of Orthopedics The Fourth Central Hospital of Baoding CityBaoding072350China

The osteochondral defect repair has been most extensively studied due to the rising demand for new therapies to diseases such as osteoarthritis.Tissue engineering has been proposed as a promising strategy to meet the demand of simultaneous regeneration of both cartilage and subchondral bone by constructing integrated gradient tissue-engineered osteochondral scaffold(IGTEOS).This review brought forward the main challenges of establishing a satisfactory IGTEOS from the perspectives of the complexity of physiology and microenvironment of osteochondral tissue,and the limitations of obtaining the desired and required scaffold.Then,we comprehensively discussed and summarized the current tissue-engineered efforts to resolve the above challenges,including architecture strategies,fabrication techniques and in vitro/in vivo evaluation methods of the IGTEOS.Especially,we highlighted the advantages and limitations of various fabrication techniques of IGTEOS,and common cases of IGTEOS application.Finally,based on the above challenges and current research progress,we analyzed in details the future perspectives of tissue-engineered osteochondral construct,so as to achieve the perfect reconstruction of the cartilaginous and osseous layers of osteochondral tissue simultaneously.This comprehensive and instructive review could provide deep insights into our current understanding of IGTEOS.

关键词： Osteochondral tissue engineering Integrated gradient tissue-engineered osteochondral scaffold(IGTEOS) Tissue-engineered strategies Fabrication techniques Evaluation

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