Biofabrication of nanocomposite-based scaffolds containing human bone extracellularmatrix for the differentiation of skeletal stem and progenitor cells

Autograft or metal implants are routinely used in skeletal repair.However,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering alternative.The use of native human bone tissue for synthesizing a biomimeticmaterial inkfor three-dimensional(3D)bioprintingof skeletal tissueis anattractivestrategyfor tissueregeneration.Thus,human bone extracellular matrix(bone-ECM)offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells(HBMSCs)to proliferate and differentiate along the osteogenic lineage.In this study,we engineered a novel material ink(LAB)by blending human bone-ECM(B)with nanoclay(L,Laponite®)and alginate(A)polymers using extrusion-based deposition.The inclusion of the nanofiller and polymeric material increased the rheology,printability,and drug retention properties and,critically,the preservation of HBMSCs viability upon printing.The composite of human bone-ECM-based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane(CAM)model.The inclusion of bone morphogenetic protein-2(BMP-2)with the HBMSCs further enhanced vascularization and mineralization after only seven days.This study demonstrates the synergistic combination of nanoclay with biomimetic materials(alginate and bone-ECM)to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.

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.

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

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 integrity.This 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 correlation.Although 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 preserved.Structural 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 corrosion.However,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.