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

Additive manufacturing(AM)has revolutionized the design and manufacturing of patient-specific,three-dimensional(3D),complex porous structures known as scaffolds for tissue engineering applications.The 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 scaffolds.However,these sophisticated techniques can be timeconsuming,labor-intensive,and expensive.Moreover,the necessary imaging and manufacturing equipment may not be readily available when urgent treatment is needed for trauma patients.In 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 patient.These 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 surgery.The 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 segmentation.This algorithm can generate both patient-specific and average bone models.Additionally,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 images.The algorithms are implemented,and the designed scaffold blocks are 3D printed using an extrusion-based AM process.Guidelines and instructions are also provided to assist surgeons in assembling scaffold blocks for the self-repair of patient-specific large bone defects.

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

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.

Development of Muscle Tendon Junction in vitro Using Aligned Electrospun PCL Fibres

The muscle tendon junction(MTJ)transmits the force generated by the muscle to the tendon and ultimately to the bone.Tears and strains commonly occur at the MTJ where regeneration is limited due poor vascularisation and the complexity of the tissue.Currently treatments for a complete MTJ tear are often unsuccessful.The creation of a tissue engineered MTJ would therefore be beneficial in the development of a novel treatment.In this study,aligned electrospun polycaprolactone fibres were fabricated and human myoblasts and tenocytes were cultured on the scaffold.The effect of 10%cyclic strain and co-culture of myoblasts and tenocytes on the MTJ formation was investigated.The application of strain significantly increased cell elongation,and MTJ marker gene expression.Co-culture of myoblasts and tenocytes with strain induced higher MTJ marker gene expression compared with myoblasts and tenocytes cultured separately.Paxillin and collagen 22,naturally found in the MTJ,were also produced when cells were combined and grown in a 10%strain environment.For the first time these results showed that the combination of the strain and co-culture of myoblasts and tenocytes promotes gene expression and production of proteins that are found in the MTJ.

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

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 use.To overcome these problems,a tight seal associated with the epidermal and dermal adhesion to the implant is crucial.This 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 keratinocytes.The intraosseous transcutaneous amputation prosthesis is a new device with a pylon and a flange,which is specifically designed for optimising soft tissue attachment.Previously 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 implants.The 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 implant.At 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 drilling.The pore sizes of the ALM flanges were 700,1000 and 1250μm.We hypothesised that ALM porous flanges would reduce downgrowth,improve soft tissue integration and revascularisation compared with machined controls.The results supported our hypothesis with significantly greater soft tissue integration and revascularisation in ALM porous flanges compared with machined controls.