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Customized scaffolds for large bone defects using 3D‑printed modular blocks from 2D‑medical images

Bio-Design and Manufacturing 2024年第1期7卷 74-87页

作者： Anil AAcar Evangelos Daskalakis Paulo Bartolo Andrew Weightman Glen Cooper gordon blunn Bahattin Koc Faculty of Engineering and Natural Sciences Sabanci UniversityIstanbul 34956Türkiye D Bioprinting Laboratory Sabanci University Nanotechnology Research and Application CenterIstanbul 34956Türkiye School of Mechanical Aerospace and Civil EngineeringManchester Institute of BiotechnologyUniversity of ManchesterManchester M139PLUK Singapore Centre for 3D Printing School of Mechanical and Aerospace EngineeringNanyang Technological UniversitySingapore 639798Singapore School of Pharmacy and Biomedical Sciences University of PortsmouthPortsmouth PO12UPUK

Additive manufacturing(AM)has revolutionized the design and manufacturing of patient-specific,three-dimensional(3D),complex porous structures known as scaffolds for tissue engineering *** use of advanced image acquisition techniques,image processing,and computer-aided design methods has enabled the precise design and additive manufacturing of anatomically correct and patient-specific implants and ***,these sophisticated techniques can be timeconsuming,labor-intensive,and ***,the necessary imaging and manufacturing equipment may not be readily available when urgent treatment is needed for trauma *** this study,a novel design and AM methods are proposed for the development of modular and customizable scaffold blocks that can be adapted to fit the bone defect area of a *** modular scaffold blocks can be combined to quickly form any patient-specific scaffold directly from two-dimensional(2D)medical images when the surgeon lacks access to a 3D printer or cannot wait for lengthy 3D imaging,modeling,and 3D printing during *** proposed method begins with developing a bone surface-modeling algorithm that reconstructs a model of the patient’s bone from 2D medical image measurements without the need for expensive 3D medical imaging or *** algorithm can generate both patient-specific and average bone ***,a biomimetic continuous path planning method is developed for the additive manufacturing of scaffolds,allowing porous scaffold blocks with the desired biomechanical properties to be manufactured directly from 2D data or *** algorithms are implemented,and the designed scaffold blocks are 3D printed using an extrusion-based AM *** and instructions are also provided to assist surgeons in assembling scaffold blocks for the self-repair of patient-specific large bone defects.

关键词： Additive manufacturing Modular scaffolds Large bone defect Customized scaffold design Patient-specific scaffolds

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Open-porous magnesium-based scaffolds withstand in vitro corrosion under cyclic loading:A mechanistic study

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Bioactive Materials 2023年第1期19卷 406-417页

作者： Roxane Bonithon Colin Lupton Marta Roldo Joseph Nicholas Dunlop gordon William blunn Frank Witte Gianluca Tozzi Zeiss Global Centre School of Mechanical and Design EngineeringUniversity of PortsmouthAnglesea RoadPO13DJPortsmouthUnited Kingdom School of Pharmacy and Biomedical Sciences University of PortsmouthWhite Swan RoadPO12DTPortsmouthUnited Kingdom School of the Environment Geography&GeosciencesUniversity of PortsmouthBurnaby RoadPO13QLPortsmouthUnited Kingdom Department of Prosthodontics Geriatric Dentistry and Craniomandibular DisordersCharite-Universitätsmedizin BerlinAßmannshauser Straße 4-614197BerlinGermany Biotrics Bioimplants AG Ullsteinstr.10812109BerlinGermany

The successful application of magnesium(Mg)alloys as biodegradable bone substitutes for critical-sized defects may be comprised by their high degradation rate resulting in a loss of mechanical *** study investigates the degradation pattern of an open-porous fluoride-coated Mg-based scaffold immersed in circulating Hanks’Balanced Salt Solution(HBSS)with and without in situ cyclic compression(30 N/1 Hz).The changes in morphological and mechanical properties have been studied by combining in situ high-resolution X-ray computed tomography mechanics and digital volume *** in situ cyclic compression induced acceleration of the corrosion rate,probably due to local disruption of the coating layer where fatigue microcracks were formed,no critical failures in the overall scaffold were observed,indicating that the mechanical integrity of the Mg scaffolds was *** changes,due to the accumulation of corrosion debris between the scaffold fibres,resulted in a significant increase(p<0.05)in the material volume fraction from 0.52±0.07 to 0.47±0.03 after 14 days of ***,despite an increase in fibre material loss,the accumulated corrosion products appear to have led to an increase in Young’s modulus after 14 days as well as lower third principal strain(εp3)accumulation(-91000±6361μεand-60093±2414μεafter 2 and 14 days,respectively).Therefore,this innovative Mg scaffold design and composition provide a bone replacement,capable of sustaining mechanical loads in situ during the postoperative phase allowing new bone formation to be initially supported as the scaffold resorbs.

关键词： Magnesium alloys Bone regeneration In vitro corrosion X-ray computed tomography(XCT) Digital volume correlation(DVC)

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Optimising soft tissue in-growth in vivo in additive layer manufactured osseointegrated transcutaneous implants

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Biomaterials Translational 2022年第4期3卷 243-249页

作者： Elena Giusto gordon blunn Roberta Ferro de Godoy Chaozong Liu Catherine Pendegrass Institute of Orthopaedic&Musculoskeletal Science University College LondonRoyal National Orthopaedic HospitalStanmoreUK Barts and the London School of Medicine and Dentistry Queen Mary University LondonLondonUK School of Pharmacy and Biomedical Sciences University of PortsmouthPortsmouthUK Writtle University College WrittleUK

Osseointegrated transcutaneous implants could provide an alternative and improved means of attaching artificial limbs for amputees,however epithelial down growth,inflammation,and infections are common failure modalities associated with their *** overcome these problems,a tight seal associated with the epidermal and dermal adhesion to the implant is *** could be achieved with specific biomaterials(that mimic the surrounding tissue),or a tissue-specific design to enhance the proliferation and attachment of dermal fibroblasts and *** intraosseous transcutaneous amputation prosthesis is a new device with a pylon and a flange,which is specifically designed for optimising soft tissue *** the flange has been fabricated using traditional machining techniques,however,the advent of additive layer manufacturing(ALM)has enabled 3-dimensional porous flanges with specific pore sizes to be used to optimise soft tissue integration and reduce failure of osseointegrated transcutaneous *** study aimed to investigate the effect of ALM-manufactured porous flanges on soft tissue ingrowth and attachment in an in vivo ovine model that replicates an osseointegrated percutaneous *** 12 and 24 weeks,epithelial downgrowth,dermal attachment and revascularisation into ALM-manufactured flanges with three different pore sizes were compared with machined controls where the pores were made using conventional *** pore sizes of the ALM flanges were 700,1000 and 1250μ*** hypothesised that ALM porous flanges would reduce downgrowth,improve soft tissue integration and revascularisation compared with machined *** results supported our hypothesis with significantly greater soft tissue integration and revascularisation in ALM porous flanges compared with machined controls.

关键词： in-vivo model ITAP orthopaedic implants osseointegrated transcutaneous implants

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In vivo evaluation of additively manufacturedmulti-layered scaffold for the repair of large osteochondral defects

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Bio-Design and Manufacturing 2022年第3期5卷 481-496页

作者： Maryam Tamaddon gordon blunn Rongwei Tan Pan Yang Xiaodan Sun Shen-Mao Chen Jiajun Luo Ziyu Liu Ling Wang Dichen Li Ricardo Donate Mario Monzón Chaozong Liu Institute of Orthopaedic and Musculoskeletal Science Royal National Orthopaedic HospitalUniversity College LondonStanmore HA74LPUK School of Pharmacy and Biomedical Sciences University of PortsmouthPortsmouth PO12DTUK Guangdong Engineering Research Center of Implantable Medical Polymer Shenzhen Lando Biomaterials Co.Ltd.Shenzhen 518107China School of Materials Science and Engineering Tsinghua UniversityBeijing 100084China State Key Laboratory for Manufacturing System Engineering School of Mechanical EngineeringXi’an Jiaotong UniversityXi’an 710054China Departamento de Ingeniería Mecánica Grupo de Investigación en Fabricación Integrada y AvanzadaUniversidad de Las Palmas de Gran CanariaCampus Universitario de Tafira s/n35017 Las PalmasSpain

The repair of osteochondral defects is one of the major clinical challenges in ***-established osteochondral tissue engineering methods have shown promising results for the early treatment of small ***,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 *** 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 *** developed scaffold is based on a titanium and polylactic acid matrix-reinforced collagen“sandwich”composite *** 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 *** 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 *** histological examination showed that the regenerated cartilage in the multi-layer scaffold group was superior to that formed in the control *** genes such as aggrecan and collagen-II were upregulated in the scaffold and were higher than those in the control *** 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.

关键词： Osteochondral scaffold Large animal Additive manufacturing Porous titanium

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Role of nanotopography in the development of tissue engineered 3D organs and tissues using mesenchymal stem cells

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World Journal of Stem Cells 2015年第2期7卷 266-280页

作者： Shima Salmasi Deepak M Kalaskar Wai-Weng Yoon gordon W blunn Alexander M Seifalian UCL Division of Surgery and Interventional Science Centre for Nanotechnology and Regenerative MedicineUniversity College London Royal National Orthopaedic Hospital Institute of Orthopaedics and MusculoSkeletal Science University College London Institute of Orthopaedics and MusculoSkeletal Science Royal National Orthopaedic Hospital

Recent regenerative medicine and tissue engineering strategies(using cells, scaffolds, medical devices and gene therapy) have led to fascinating progress of translation of basic research towards clinical applications. In the past decade, great deal of research has focused on developing various three dimensional(3D) organs, such as bone, skin, liver, kidney and ear,using such strategies in order to replace or regenerate damaged organs for the purpose of maintaining or restoring organs' functions that may have been lost due to aging, accident or disease. The surface properties of a material or a device are key aspects in determining the success of the implant in biomedicine, as the majority of biological reactions in human body occur on surfaces or interfaces. Furthermore, it has been established in the literature that cell adhesion and proliferation are, to a great extent, influenced by the micro- and nanosurface characteristics of biomaterials and devices. In addition, it has been shown that the functions of stem cells, mesenchymal stem cells in particular, could be regulated through physical interaction with specific nanotopographical cues. Therefore, guided stem cell proliferation, differentiation and function are of great importance in the regeneration of 3D tissues and organs using tissue engineering strategies. This review will provide an update on the impact of nanotopography on mesenchymal stem cells for the purpose of developing laboratory-based 3D organs and tissues, as well as the most recent research and case studies on this topic.

关键词： Nanotopography Mesenchymal stem cells Tissue engineering Nanotechnology Three dimensionalorgans/tissues Scaffolds

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