To get an optimal product of orthopaedic implant or regenerative medicine needs to follow trialand-error analyses to investigate suitable product’s material,structure,mechanical properites etc.The whole process from ...To get an optimal product of orthopaedic implant or regenerative medicine needs to follow trialand-error analyses to investigate suitable product’s material,structure,mechanical properites etc.The whole process from in vivo tests to clinical trials is expensive and time-consuming.Computational model is seen as a useful analysis tool to make the product development.A series of models for simulating tissue engineering process from cell attachment to tissue regeneration are reviewed.The challenging is that models for simulating tissue engineering processes are developed separately.From cell to tissue regeneration,it would go through blood injection after moving out the defect;to cell disperse and attach on the scaffold;to proliferation,migration and differentiation;and to the final part-becoming mature tissues.This paper reviewed models that related to tissue engineering process,aiming to provide an opportunity for researchers to develop a mature model for whole tissue engineering process.This article focuses on the model analysis methods of cell adhesion,nutrient transport and cell proliferation,differentiation and migration in tissue engineering.In cell adhesion model,one of the most accurate method is to use discrete phase model to govern cell movement and use Stanton-Rutland model for simulating cell attachment.As for nutrient transport model,numerical model coupling with volume of fluid model and species transport model together is suitable for predicting nutrient transport process.For cell proliferation,differentiation and migration,finite element method with random-walk algorithm is one the most advanced way to simulate these processes.Most of the model analysis methods require further experiments to verify the accuracy and effectiveness.Due to the lack of technology to detect the rate of nutrient diffusion,there are especially few researches on model analysis methods in the area of blood coagulation.Therefore,there is still a lot of work to be done in the research of the whole process model method of tissue engineering.In the future,the numerical model would be seen as an optimal way to investigate tissue engineering products bioperformance and also enable to optimize the parameters and material types of the tissue engineering products.展开更多
The repair of osteochondral defects is one of the major clinical challenges in orthopaedics.Well-established osteochondral tissue engineering methods have shown promising results for the early treatment of small defec...The repair of osteochondral defects is one of the major clinical challenges in orthopaedics.Well-established osteochondral tissue engineering methods have shown promising results for the early treatment of small defects.However,less success has been achieved for the regeneration of large defects,which is mainly due to the mechanical environment of the joint and the heterogeneous nature of the tissue.In this study,we developed a multi-layered osteochondral scaffold to match the heterogeneous nature of osteochondral tissue by harnessing additive manufacturing technologies and combining the established art laser sintering and material extrusion techniques.The developed scaffold is based on a titanium and polylactic acid matrix-reinforced collagen“sandwich”composite system.The microstructure and mechanical properties of the scaffold were examined,and its safety and efficacy in the repair of large osteochondral defects were tested in an ovine condyle model.The 12-week in vivo evaluation period revealed extensive and significantly higher bone in-growth in the multi-layered scaffold compared with the collagen–HAp scaffold,and the achieved stable mechanical fixation provided strong support to the healing of the overlying cartilage,as demonstrated by hyaline-like cartilage formation.The histological examination showed that the regenerated cartilage in the multi-layer scaffold group was superior to that formed in the control group.Chondrogenic genes such as aggrecan and collagen-II were upregulated in the scaffold and were higher than those in the control group.The findings showed the safety and efficacy of the cell-free“translation-ready”osteochondral scaffold,which has the potential to be used in a one-step surgical procedure for the treatment of large osteochondral defects.展开更多
TiO2 nanotubes(NT)has been demonstrated its potential in orthopaedic applications due to its enhanced surface wettability and bio-osteointegration.However,the fretting biocorrosion is the main concern that limited its...TiO2 nanotubes(NT)has been demonstrated its potential in orthopaedic applications due to its enhanced surface wettability and bio-osteointegration.However,the fretting biocorrosion is the main concern that limited its successfully application in orthopaedic application.In this study,a structure optimised thin TiO2 nanotube(SONT)layer was successfully created on Ti6Al4V bone screw,and its fretting corrosion performance was investigated and compared to the pristine Ti6Al4V bone screws and NT decorated screw in a bone-screw fretting simulation rig.The results have shown that the debonding TiO2 nanotube from the bone screw reduced significantly,as a result of structure optimisation.The SONT layer also exhibited enhanced bio-corrosion resistance compared pristine bone screw and conventionally NT modified bone screw.It is postulated that interfacial layer between TiO2 nanotube and Ti6Al4V substrate,generated during structure optimisation process,enhanced bonding of TiO2 nanotube layer to the Ti6Al4V bone screws that leading to the improvement in fretting corrosion resistance.The results highlighted the potential SONT in orthopaedic application as bone fracture fixation devices.展开更多
In the field of tissue engineering,there is significant subsidence of the porous design scaffold several months after implantation.To avoid stress shielding and stimulate bone and cartilage ingrowth,high scaffold poro...In the field of tissue engineering,there is significant subsidence of the porous design scaffold several months after implantation.To avoid stress shielding and stimulate bone and cartilage ingrowth,high scaffold porosity is needed to diminish the mechanical properties of the scaffold.The closer the mechanical properties of the scaffold are to those of surrounding tissues,the better biological properties it will get.Besides,adequate mechanical stability is needed as the scaffold needs to be well fixed in the target area and it will endure load after surgery.Evaluating the mechanical fixation of the scaffold at the initial stage and the long-term performance of a scaffold for in vivo study is hard,as no facility can be put into the target area for the friction test.This study investigated the mechanical stability of the biomimetic scaffold at the initial stage of implantation by finite element analysis(FEA).According to in vivo study,scaffold could not maintain its original position and would sink 1-2 mm in the target area.The simulation results suggested that mechanical loading is not the main reason for scaffold subsidence.展开更多
Osteoarthritis （OA）, identified as one of the priorities for the Bone and Joint Decade, is one of the most prevalent joint diseases, which causes pain and disability of joints in the adult population. Secondary OA u...Osteoarthritis （OA）, identified as one of the priorities for the Bone and Joint Decade, is one of the most prevalent joint diseases, which causes pain and disability of joints in the adult population. Secondary OA usually stems from repetitive overloading to the osteochondral （OC） unit, which could result in cartilage damage and changes in the subchondral bone, leading to mechanical instability of the joint and loss of joint function. Tissue engineering approaches have emerged for the repair of cartilage defects and damages to the subchondral bone in the early stages of OA and have shown potential in restoring the joint＇s function. In this approach, the use of three-dimensional scaffolds （with or without cells） provides support for tissue growth. Commercially available OC scaffolds have been studied in OA patients for repair and regeneration of OC defects. However, none of these scaffolds has shown satisfactory clinical results. This article reviews the OC tissue structure and the design, manufacturing and performance of current OC scaffolds in treatment of OA. The findings demonstrate the importance of biological and biomechanical fixations of OC scaffolds to the host tissue in achieving an improved cartilage fill and a hyaline-like tissue formation. Achieving a strong and stable subchondral bone support that helps the regeneration of overlying cartilage seems to be still a grand challenge for the early treatment of OA.展开更多
Nutrients supply especially like nutrients and oxygen play vital role in tissue engineering process.It is found that tissue could not grow very well in the middle of the scaffold because few nutrients could transport ...Nutrients supply especially like nutrients and oxygen play vital role in tissue engineering process.It is found that tissue could not grow very well in the middle of the scaffold because few nutrients could transport to the middle.Nutrient limitations would reduce cell proliferation and differentiation.In that case,there is urgent need to understand the nutrient distribution for both in vitro and in vivo study,as no technology is able for researchers to observe the nutrients transport during those process.In this paper,a numerical model coupling with VOF(volume of fluid)model and species transport model together for predicting the distribution of oxygen and glucose in the scaffold after implantation in to the site is developed.Comparing with our previous in vivo tests,the regenerated tissue distribution has a similar trend as oxygen distribution rather than glucose.The reported scaffold manufactured by additive manufacturing provided a good interconnected structure which facilitated the nutrient transportation in the scaffold.Considering nutrient transportation,this numerical model could be used in better understanding the nutrients transportation in the scaffold,and leading to a better understanding of tissue formation in the scaffold.展开更多
When biomaterials are implanted in the human body,the surfaces of the implants become favorable sites for microbial adhesion and biofilm formation,causing peri-implant infection which frequently results in the failure...When biomaterials are implanted in the human body,the surfaces of the implants become favorable sites for microbial adhesion and biofilm formation,causing peri-implant infection which frequently results in the failure of prosthetics and revision surgery.Ti-Mo alloy is one of the commonly used implant materials for load-bearing bone replacement,and the prevention of infection of Ti-Mo implants is therefore crucial.In this study,bacterial inhibitory copper(Cu)was added to Ti-Mo matrix to develop a novel Ti-Mo-Cu alloy with bacterial inhibitory property.The effects of Cu content on microstructure,tensile properties,cytocompatibility,and bacterial inhibitory ability of Ti-Mo-Cu alloy were systematically investigated.Results revealed that Ti-10Mo-1Cu alloy consisted ofαandβphases,while there were a few Ti2Cu intermetallic compounds existed for Ti-10Mo-3Cu and Ti-10Mo-5Cu alloys,in addition toαandβphases.The tensile strength of Ti-10Mo-xCu alloy increased with Cu content while elongation decreased.Ti-10Mo-3Cu alloy exhibited an optimal tensile strength of 1098.1 MPa and elongation of 5.2%.Cytocompatibility study indicated that none of the Ti-10Mo-xCu alloys had a negative effect on MC3T3-E1 cell proliferation.Bacterial inhibitory rates against S.aureus and E.coli increased with the increase in Cu content of Ti-10Mo-xCu alloy,within the ranges of 20-60%and 15-50%,respectively.Taken together,this study suggests that Ti-10Mo-3Cu alloy with high strength,acceptable elongation,excellent cytocompatibility,and the bacterial inhibitory property is a promising candidate for biomedical implant applications.展开更多
Ti alloys with lattice structures are garnering more and more attention in the field of bone repair or regeneration due to their superior structural,mechanical,and biological properties.In this study,six types of comp...Ti alloys with lattice structures are garnering more and more attention in the field of bone repair or regeneration due to their superior structural,mechanical,and biological properties.In this study,six types of composite lattice structures with different strut radius that consist of simple cubic(structure A),body-centered cubic(structure B),and edge-centered cubic(structure C)unit cells are designed.The designed structures are firstly simulated and analysed by the finite element(FE)method.Commercially pure Ti(CP-Ti)lattice structures with optimized unit cells and strut radius are then fabricated by selective laser melting(SLM),and the dimensions,microtopography,and mechanical properties are characterised.The results show that among the six types of composite lattice structures,combined BA,CA,and CB structures exhibit smaller maximum von-Mises stress,indicating that these structures have higher strength.Based on the fitting curves of stress/specific surface area versus strut radius,the optimized strut radius of BA,CA,and CB structures is 0.28,0.23,and 0.30 mm respectively.Their corresponding compressive yield strength and compressive modulus are 42.28,30.11,and 176.96 MPa,and 4.13,2.16,and 7.84 GPa,respectively.The CP-Ti with CB unit structure presents a similar strength and compressive modulus to the cortical bone,which makes it a potential candidate for subchondral bone restorations.展开更多
Osteoarthritis is a degenerative joint disease,typified by the loss in the quality of cartilage and bone at the interface of a synovial joint,resulting in pain,stiffness and reduced mobility.The current surgical treat...Osteoarthritis is a degenerative joint disease,typified by the loss in the quality of cartilage and bone at the interface of a synovial joint,resulting in pain,stiffness and reduced mobility.The current surgical treatment for advanced stages of the disease is joint replacement,where the non-surgical therapeutic options or less invasive surgical treatments are no longer effective.These are major surgical procedures which have a substantial impact on patients’quality of life and lifetime risk of requiring revision surgery.Treatments using regenerative methods such as tissue engineering methods have been established and are promising for the early treatment of cartilage degeneration in osteoarthritis joints.In this approach,3-dimensional scaffolds(with or without cells)are employed to provide support for tissue growth.However,none of the currently available tissue engineering and regenerative medicine products promotes satisfactory durable regeneration of large cartilage defects.Herein,we discuss the current regenerative treatment options for cartilage and osteochondral(cartilage and underlying subchondral bone)defects in the articulating joints.We further identify the main hurdles in osteochondral scaffold development for achieving satisfactory and durable regeneration of osteochondral tissues.The evolution of the osteochondral scaffolds–from monophasic to multiphasic constructs–is overviewed and the osteochondral scaffolds that have progressed to clinical trials are examined with respect to their clinical performances and their potential impact on the clinical practices.Development of an osteochondral scaffold which bridges the gap between small defect treatment and joint replacement is still a grand challenge.Such scaffold could be used for early treatment of cartilage and osteochondral defects at early stage of osteoarthritis and could either negate or delay the need for joint replacements.展开更多
Polyether-ether-ketone(PEEK)is widely used in producing prosthesis and have gained great attention for repair of large bone defect in recent years with the development of additive manufacturing.This is due to its exce...Polyether-ether-ketone(PEEK)is widely used in producing prosthesis and have gained great attention for repair of large bone defect in recent years with the development of additive manufacturing.This is due to its excellent biocompatibility,good heat and chemical stability and similar mechanical properties which mimics natural bone.In this study,three replicates of rectilinear scaffolds were designed for compression,tension,three-point bending and torsion test with unit cell size of 0.8 mm,a pore size of 0.4 mm,strut thickness of 0.4 mm and nominal porosity of 50%.Stress-strain graphs were developed from experimental and finite element analysis models.Experimental Young’s modulus and yield strength of the scaffolds were measured from the slop of the stress-strain graph to be 395 and 19.50 MPa respectively for compression,427 and 6.96 MPa respectively for tension,257 and 25.30 MPa respectively for three-point bending and 231 and 12.83 MPa respectively for torsion test.The finite element model was found to be in good agreement with the experimental results.Ductile fracture of the struct subjected to tensile strain was the main failure mode of the PEEK scaffold,which stems from the low crystallinity of additive manufacturing PEEK.The mechanical properties of porous PEEK are close to those of cancellous bone and thus are expected to be used in additive manufacturing PEEK bone implants in the future,but the lower yield strength poses a design challenge.展开更多
Osteoarthritis is the most common chronic degenerative joint disease,recognized by the World Health Organization as a public health problem that affects millions of people worldwide.The project Biomaterials and Additi...Osteoarthritis is the most common chronic degenerative joint disease,recognized by the World Health Organization as a public health problem that affects millions of people worldwide.The project Biomaterials and Additive Manufacturing:Osteochondral Scaffold(BAMOS)innovation applied to osteoarthritis,funded under the frame of the Horizon 2020 Research and Innovation Staff Exchanges(RISE)program,aims to delay or avoid the use of joint replacements by developing novel cost-effective osteochondral scaffold technology for early intervention of osteoarthritis.The multidisciplinary consortium of BAMOS,formed by international leading research centres,collaborates through research and innovation staff exchanges.The project covers all the stages of the development before the clinical trials:design of scaffolds,biomaterials development,processability under additive manufacturing,in vitro test,and in vivo test.This paper reports the translational practice adopted in the project in in vivo assessment of the osteochondral scaffolds developed.展开更多
In tissue engineering field,it is important to develop a suitable numerical model to evaluate scaffold geometry design.The experimental evaluation of the effect of each specific scaffold parameter on tissue regenerati...In tissue engineering field,it is important to develop a suitable numerical model to evaluate scaffold geometry design.The experimental evaluation of the effect of each specific scaffold parameter on tissue regeneration requires large cost and long time expend.Dynamic cell culture is commonly used for generating tissues which could replace damaged tissues.A perfusion bioreactor model is developed which is able to simulate dynamic cell culture,to evaluate scaffold quality.The wall-film model is used to simulate cell attachment with the assumption that cells could be seen as liquid drops.In the process of cell attachment,the cells could impinge to a solid surface and form a liquid film which were considered as cell attached on the scaffold surface.Two types of cell-scaffold interactions were involved in numerical models including trap model and Stanton-Rutland(Cell impinge model—CIM)model.For trap model,all cells impinged the scaffold are seen as attached.For Stanton-Rutland model,four regimes of cell-scaffold interaction are involved in the cell attachment,including stick,rebound,spread,and splash,and only stick and spread are seen as attached.By comparison with two different numerical methods,the results showed that CIM model result is more related to the experimental results than trap model,which indicated that four regimes of cell-scaffold interaction occurred in cell attachment process.By evaluating two different geometry scaffold's cells seeding by these two models,the results further indicated that this model are able to use for assessing the scaffold design.展开更多
基金supported by the National Natural Science Foundation of China(Nos.51922004,51874037)State Key Lab of Advanced Metals and Materials,University of Science and Technology Beijing,China(Nos.2019Z-14,2020Z-04,2021Z-03)+7 种基金Fundamental Research Funds for the Central Universities,China(Nos.FRF-TP-19005C1Z,06500236)Interdisciplinary Research Project for Young Teachers of USTB,China(Fundamental Research Funds for the Central Universities,FRF-IDRY-20-023)Postdoctor Research Foundation of Shunde Graduate School of University of Science and Technology Beijing,China(No.2022BH001)the China Postdoctoral Science Foundation(No.2021M700377)the Beijing Natural Science Foundation,China(No.2212035)the support from the European Commission via the H2020 MSCA RISE BAMOS program(No.734156)Innovate UK via Newton Fund(No.102872)Engineering and Physical Science Research Council(EPSRC)via DTP case programme(No.EP/T517793/1)。
基金supported by the Versus Arthritis Research UK(Grant No:21977)European Commission via a H2020-MSCA-RISE programme(BAMOS,Grant No:734156)+1 种基金Innovative UK via Newton Fund(Grant No:102872)Engineering and Physical Science Research Council(EPSRC)via DTP CASE programme(Grant No:EP/T517793/1)。
文摘To get an optimal product of orthopaedic implant or regenerative medicine needs to follow trialand-error analyses to investigate suitable product’s material,structure,mechanical properites etc.The whole process from in vivo tests to clinical trials is expensive and time-consuming.Computational model is seen as a useful analysis tool to make the product development.A series of models for simulating tissue engineering process from cell attachment to tissue regeneration are reviewed.The challenging is that models for simulating tissue engineering processes are developed separately.From cell to tissue regeneration,it would go through blood injection after moving out the defect;to cell disperse and attach on the scaffold;to proliferation,migration and differentiation;and to the final part-becoming mature tissues.This paper reviewed models that related to tissue engineering process,aiming to provide an opportunity for researchers to develop a mature model for whole tissue engineering process.This article focuses on the model analysis methods of cell adhesion,nutrient transport and cell proliferation,differentiation and migration in tissue engineering.In cell adhesion model,one of the most accurate method is to use discrete phase model to govern cell movement and use Stanton-Rutland model for simulating cell attachment.As for nutrient transport model,numerical model coupling with volume of fluid model and species transport model together is suitable for predicting nutrient transport process.For cell proliferation,differentiation and migration,finite element method with random-walk algorithm is one the most advanced way to simulate these processes.Most of the model analysis methods require further experiments to verify the accuracy and effectiveness.Due to the lack of technology to detect the rate of nutrient diffusion,there are especially few researches on model analysis methods in the area of blood coagulation.Therefore,there is still a lot of work to be done in the research of the whole process model method of tissue engineering.In the future,the numerical model would be seen as an optimal way to investigate tissue engineering products bioperformance and also enable to optimize the parameters and material types of the tissue engineering products.
基金financially supported by the Versus Arthritis (No. 21160)the Rosetree Trust (No. A1184)+2 种基金the European Commission via H2020-MSCA-RISE Program (BAMOS Project (No.734156))Innovate UK via Newton Fund (No. 102872)the Engineering and Physical Science Research Council (EPSRC) via DTP Case Programme (No. EP/T517793/1)
文摘The repair of osteochondral defects is one of the major clinical challenges in orthopaedics.Well-established osteochondral tissue engineering methods have shown promising results for the early treatment of small defects.However,less success has been achieved for the regeneration of large defects,which is mainly due to the mechanical environment of the joint and the heterogeneous nature of the tissue.In this study,we developed a multi-layered osteochondral scaffold to match the heterogeneous nature of osteochondral tissue by harnessing additive manufacturing technologies and combining the established art laser sintering and material extrusion techniques.The developed scaffold is based on a titanium and polylactic acid matrix-reinforced collagen“sandwich”composite system.The microstructure and mechanical properties of the scaffold were examined,and its safety and efficacy in the repair of large osteochondral defects were tested in an ovine condyle model.The 12-week in vivo evaluation period revealed extensive and significantly higher bone in-growth in the multi-layered scaffold compared with the collagen–HAp scaffold,and the achieved stable mechanical fixation provided strong support to the healing of the overlying cartilage,as demonstrated by hyaline-like cartilage formation.The histological examination showed that the regenerated cartilage in the multi-layer scaffold group was superior to that formed in the control group.Chondrogenic genes such as aggrecan and collagen-II were upregulated in the scaffold and were higher than those in the control group.The findings showed the safety and efficacy of the cell-free“translation-ready”osteochondral scaffold,which has the potential to be used in a one-step surgical procedure for the treatment of large osteochondral defects.
基金financially supported by the European Union via the H2020-MSCA-RISE-2016 program(BAMOS Project,734156)Royal Society via the International Exchange Program(IE161349)+2 种基金Key Research Project from the National Key Research and Development Program of China(2016YFC1100401)National Natural Science Foundation of China(51705507)Young Elite Scientists Sponsorship Program by CAST(2017QNRC0181)。
文摘TiO2 nanotubes(NT)has been demonstrated its potential in orthopaedic applications due to its enhanced surface wettability and bio-osteointegration.However,the fretting biocorrosion is the main concern that limited its successfully application in orthopaedic application.In this study,a structure optimised thin TiO2 nanotube(SONT)layer was successfully created on Ti6Al4V bone screw,and its fretting corrosion performance was investigated and compared to the pristine Ti6Al4V bone screws and NT decorated screw in a bone-screw fretting simulation rig.The results have shown that the debonding TiO2 nanotube from the bone screw reduced significantly,as a result of structure optimisation.The SONT layer also exhibited enhanced bio-corrosion resistance compared pristine bone screw and conventionally NT modified bone screw.It is postulated that interfacial layer between TiO2 nanotube and Ti6Al4V substrate,generated during structure optimisation process,enhanced bonding of TiO2 nanotube layer to the Ti6Al4V bone screws that leading to the improvement in fretting corrosion resistance.The results highlighted the potential SONT in orthopaedic application as bone fracture fixation devices.
基金financially supported by Versus Arthritis Research UK (No.21977)European Commission via a H2020-MSCA-RISE Programme (BAMOS,No.734156)+2 种基金Innovative UK via Newton Fund (No.102872)Engineering and Physical Science Research Council (EPSRC) via DTP CASE Programme (No.EP/T517793/1)the Intergovernmental Cooperation in Science and Technology of China (No.2016YFE0125300)
文摘In the field of tissue engineering,there is significant subsidence of the porous design scaffold several months after implantation.To avoid stress shielding and stimulate bone and cartilage ingrowth,high scaffold porosity is needed to diminish the mechanical properties of the scaffold.The closer the mechanical properties of the scaffold are to those of surrounding tissues,the better biological properties it will get.Besides,adequate mechanical stability is needed as the scaffold needs to be well fixed in the target area and it will endure load after surgery.Evaluating the mechanical fixation of the scaffold at the initial stage and the long-term performance of a scaffold for in vivo study is hard,as no facility can be put into the target area for the friction test.This study investigated the mechanical stability of the biomimetic scaffold at the initial stage of implantation by finite element analysis(FEA).According to in vivo study,scaffold could not maintain its original position and would sink 1-2 mm in the target area.The simulation results suggested that mechanical loading is not the main reason for scaffold subsidence.
文摘Osteoarthritis （OA）, identified as one of the priorities for the Bone and Joint Decade, is one of the most prevalent joint diseases, which causes pain and disability of joints in the adult population. Secondary OA usually stems from repetitive overloading to the osteochondral （OC） unit, which could result in cartilage damage and changes in the subchondral bone, leading to mechanical instability of the joint and loss of joint function. Tissue engineering approaches have emerged for the repair of cartilage defects and damages to the subchondral bone in the early stages of OA and have shown potential in restoring the joint＇s function. In this approach, the use of three-dimensional scaffolds （with or without cells） provides support for tissue growth. Commercially available OC scaffolds have been studied in OA patients for repair and regeneration of OC defects. However, none of these scaffolds has shown satisfactory clinical results. This article reviews the OC tissue structure and the design, manufacturing and performance of current OC scaffolds in treatment of OA. The findings demonstrate the importance of biological and biomechanical fixations of OC scaffolds to the host tissue in achieving an improved cartilage fill and a hyaline-like tissue formation. Achieving a strong and stable subchondral bone support that helps the regeneration of overlying cartilage seems to be still a grand challenge for the early treatment of OA.
基金supported by Versus Arthritis UK(Grant no:21977)European Commission via a H2020-MSCA-RISE programme(BAMOS,Grant no:734156)+1 种基金Innovative UK via Newton Fund(Grant no:102872)Engineering and Physical Science Research Council(EPSRC)via DTP CASE programme(Grant no:EP/T517793/1).
文摘Nutrients supply especially like nutrients and oxygen play vital role in tissue engineering process.It is found that tissue could not grow very well in the middle of the scaffold because few nutrients could transport to the middle.Nutrient limitations would reduce cell proliferation and differentiation.In that case,there is urgent need to understand the nutrient distribution for both in vitro and in vivo study,as no technology is able for researchers to observe the nutrients transport during those process.In this paper,a numerical model coupling with VOF(volume of fluid)model and species transport model together for predicting the distribution of oxygen and glucose in the scaffold after implantation in to the site is developed.Comparing with our previous in vivo tests,the regenerated tissue distribution has a similar trend as oxygen distribution rather than glucose.The reported scaffold manufactured by additive manufacturing provided a good interconnected structure which facilitated the nutrient transportation in the scaffold.Considering nutrient transportation,this numerical model could be used in better understanding the nutrients transportation in the scaffold,and leading to a better understanding of tissue formation in the scaffold.
基金supported by the National Natural Science Foundation of China(51922004,51874037,51672184)State Key Lab of Advanced Metals and Materials,University of Science and Technology Beijing(2019-Z14)+4 种基金Fundamental Research Funds for the Central Universities(FRF-TP-19005C1Z)the support from the European Commission via the H2020 MSCA RISE BAMOS programme(734156)Bo Su would like to thank financial support from the MRC(MR/S010343/1)the EU H2020 MSCA RISE Bio-TUNE programmethe support from the China Scholarship Council(CSC)for a CSC Ph.D.scholarship(201906460106).
文摘When biomaterials are implanted in the human body,the surfaces of the implants become favorable sites for microbial adhesion and biofilm formation,causing peri-implant infection which frequently results in the failure of prosthetics and revision surgery.Ti-Mo alloy is one of the commonly used implant materials for load-bearing bone replacement,and the prevention of infection of Ti-Mo implants is therefore crucial.In this study,bacterial inhibitory copper(Cu)was added to Ti-Mo matrix to develop a novel Ti-Mo-Cu alloy with bacterial inhibitory property.The effects of Cu content on microstructure,tensile properties,cytocompatibility,and bacterial inhibitory ability of Ti-Mo-Cu alloy were systematically investigated.Results revealed that Ti-10Mo-1Cu alloy consisted ofαandβphases,while there were a few Ti2Cu intermetallic compounds existed for Ti-10Mo-3Cu and Ti-10Mo-5Cu alloys,in addition toαandβphases.The tensile strength of Ti-10Mo-xCu alloy increased with Cu content while elongation decreased.Ti-10Mo-3Cu alloy exhibited an optimal tensile strength of 1098.1 MPa and elongation of 5.2%.Cytocompatibility study indicated that none of the Ti-10Mo-xCu alloys had a negative effect on MC3T3-E1 cell proliferation.Bacterial inhibitory rates against S.aureus and E.coli increased with the increase in Cu content of Ti-10Mo-xCu alloy,within the ranges of 20-60%and 15-50%,respectively.Taken together,this study suggests that Ti-10Mo-3Cu alloy with high strength,acceptable elongation,excellent cytocompatibility,and the bacterial inhibitory property is a promising candidate for biomedical implant applications.
基金This research work is supported by the National Natural Science Foundation of China(51922004,51874037)State Key Lab of Advanced Metals and Materials,University of Science and Technology Beijing(2019-Z14)+4 种基金Fundamental Research Funds for the Central Universities(FRF-TP-19005C1Z)Chaozong Liu acknowledges the support from the European Commission via the H2020 MSCA RISE BAMOS programme(734156)Bo Su would like to thank the financial support from the MRC(MR/S010343/1)the EU H2020 MSCA RISE Bio-TUNE programmeWei Xu acknowledges the support from the China Scholarship Council(CSC)for a CSC Ph.D.scholarship(201906460106).
文摘Ti alloys with lattice structures are garnering more and more attention in the field of bone repair or regeneration due to their superior structural,mechanical,and biological properties.In this study,six types of composite lattice structures with different strut radius that consist of simple cubic(structure A),body-centered cubic(structure B),and edge-centered cubic(structure C)unit cells are designed.The designed structures are firstly simulated and analysed by the finite element(FE)method.Commercially pure Ti(CP-Ti)lattice structures with optimized unit cells and strut radius are then fabricated by selective laser melting(SLM),and the dimensions,microtopography,and mechanical properties are characterised.The results show that among the six types of composite lattice structures,combined BA,CA,and CB structures exhibit smaller maximum von-Mises stress,indicating that these structures have higher strength.Based on the fitting curves of stress/specific surface area versus strut radius,the optimized strut radius of BA,CA,and CB structures is 0.28,0.23,and 0.30 mm respectively.Their corresponding compressive yield strength and compressive modulus are 42.28,30.11,and 176.96 MPa,and 4.13,2.16,and 7.84 GPa,respectively.The CP-Ti with CB unit structure presents a similar strength and compressive modulus to the cortical bone,which makes it a potential candidate for subchondral bone restorations.
基金This work was financially supported by the Versus Arthritis(No.21160)Rosetree Trust(No.A1184)+2 种基金European Commission via H2020 MSCA RISE BAMOS programme(No.734156)Innovative UK via Newton Fund(No.102872)and Ministry of Science and Technology of China via National Key R&D Program(No.2018YFE0207900).
文摘Osteoarthritis is a degenerative joint disease,typified by the loss in the quality of cartilage and bone at the interface of a synovial joint,resulting in pain,stiffness and reduced mobility.The current surgical treatment for advanced stages of the disease is joint replacement,where the non-surgical therapeutic options or less invasive surgical treatments are no longer effective.These are major surgical procedures which have a substantial impact on patients’quality of life and lifetime risk of requiring revision surgery.Treatments using regenerative methods such as tissue engineering methods have been established and are promising for the early treatment of cartilage degeneration in osteoarthritis joints.In this approach,3-dimensional scaffolds(with or without cells)are employed to provide support for tissue growth.However,none of the currently available tissue engineering and regenerative medicine products promotes satisfactory durable regeneration of large cartilage defects.Herein,we discuss the current regenerative treatment options for cartilage and osteochondral(cartilage and underlying subchondral bone)defects in the articulating joints.We further identify the main hurdles in osteochondral scaffold development for achieving satisfactory and durable regeneration of osteochondral tissues.The evolution of the osteochondral scaffolds–from monophasic to multiphasic constructs–is overviewed and the osteochondral scaffolds that have progressed to clinical trials are examined with respect to their clinical performances and their potential impact on the clinical practices.Development of an osteochondral scaffold which bridges the gap between small defect treatment and joint replacement is still a grand challenge.Such scaffold could be used for early treatment of cartilage and osteochondral defects at early stage of osteoarthritis and could either negate or delay the need for joint replacements.
基金The study was financially supported by National Key R&D Program of China(No.2018YFE0207900)Natural Science Basic Research Program of ShaanXi Province(No.2022JQ-378)+2 种基金The EU via the H2020-MSCA-RISE-2016 Program(No.734156)Engineering and Physical Sciences Research Council via DTP CASE Programme(No.EP/T517793/1)and Royal Society via an International Exchange Program(No.IEC\NSFC\191253).
文摘Polyether-ether-ketone(PEEK)is widely used in producing prosthesis and have gained great attention for repair of large bone defect in recent years with the development of additive manufacturing.This is due to its excellent biocompatibility,good heat and chemical stability and similar mechanical properties which mimics natural bone.In this study,three replicates of rectilinear scaffolds were designed for compression,tension,three-point bending and torsion test with unit cell size of 0.8 mm,a pore size of 0.4 mm,strut thickness of 0.4 mm and nominal porosity of 50%.Stress-strain graphs were developed from experimental and finite element analysis models.Experimental Young’s modulus and yield strength of the scaffolds were measured from the slop of the stress-strain graph to be 395 and 19.50 MPa respectively for compression,427 and 6.96 MPa respectively for tension,257 and 25.30 MPa respectively for three-point bending and 231 and 12.83 MPa respectively for torsion test.The finite element model was found to be in good agreement with the experimental results.Ductile fracture of the struct subjected to tensile strain was the main failure mode of the PEEK scaffold,which stems from the low crystallinity of additive manufacturing PEEK.The mechanical properties of porous PEEK are close to those of cancellous bone and thus are expected to be used in additive manufacturing PEEK bone implants in the future,but the lower yield strength poses a design challenge.
基金This work is part of the developments carried out in BAMOS project,funded from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No.734156.
文摘Osteoarthritis is the most common chronic degenerative joint disease,recognized by the World Health Organization as a public health problem that affects millions of people worldwide.The project Biomaterials and Additive Manufacturing:Osteochondral Scaffold(BAMOS)innovation applied to osteoarthritis,funded under the frame of the Horizon 2020 Research and Innovation Staff Exchanges(RISE)program,aims to delay or avoid the use of joint replacements by developing novel cost-effective osteochondral scaffold technology for early intervention of osteoarthritis.The multidisciplinary consortium of BAMOS,formed by international leading research centres,collaborates through research and innovation staff exchanges.The project covers all the stages of the development before the clinical trials:design of scaffolds,biomaterials development,processability under additive manufacturing,in vitro test,and in vivo test.This paper reports the translational practice adopted in the project in in vivo assessment of the osteochondral scaffolds developed.
基金This work was supported by the Versus Arthritis Research UK(Grant No:21977)European Commission via a H2020-MSCA-RISE programme(BAMOS,Grant No:734156)+2 种基金Innovative UK via Newton Fund(Grant No:102872)Engineering and Physical Science Research Council(EPSRC)via DTP CASE programme(Grant No:EP/T517793/1)Intergovernmental cooperation in science and technology of China(No.2016YFE0125300).
文摘In tissue engineering field,it is important to develop a suitable numerical model to evaluate scaffold geometry design.The experimental evaluation of the effect of each specific scaffold parameter on tissue regeneration requires large cost and long time expend.Dynamic cell culture is commonly used for generating tissues which could replace damaged tissues.A perfusion bioreactor model is developed which is able to simulate dynamic cell culture,to evaluate scaffold quality.The wall-film model is used to simulate cell attachment with the assumption that cells could be seen as liquid drops.In the process of cell attachment,the cells could impinge to a solid surface and form a liquid film which were considered as cell attached on the scaffold surface.Two types of cell-scaffold interactions were involved in numerical models including trap model and Stanton-Rutland(Cell impinge model—CIM)model.For trap model,all cells impinged the scaffold are seen as attached.For Stanton-Rutland model,four regimes of cell-scaffold interaction are involved in the cell attachment,including stick,rebound,spread,and splash,and only stick and spread are seen as attached.By comparison with two different numerical methods,the results showed that CIM model result is more related to the experimental results than trap model,which indicated that four regimes of cell-scaffold interaction occurred in cell attachment process.By evaluating two different geometry scaffold's cells seeding by these two models,the results further indicated that this model are able to use for assessing the scaffold design.
