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.

Micromesh reinforced strain sensor with high stretchability and stability for full-range and periodic human motions monitoring

The development of strain sensors with high stretchability and stability is an inevitable requirement for achieving full-range and long-term use of wearable electronic devices.Herein,a resistive micromesh reinforced strain sensor(MRSS)with high stretchability and stability is prepared,consisting of a laser-scribed graphene(LSG)layer and two styrene-block-poly(ethylene-ran-butylene)-block-poly-styrene micromesh layers embedded in Ecoflex.The micromesh reinforced structure endows the MRSS with combined characteris-tics of a high stretchability(120%),excellent stability(with a repetition error of 0.8%after 11000 cycles),and outstanding sensitivity(gauge factor up to 2692 beyond 100%).Impressively,the MRSS can still be used continauously within the working range without damage,even if stretched to 300%.Furthermore,compared with different structure sensors,the mechanism of the MRSS with high stretchability and stability is elucidated.What's more,a multilayer finite element model,based on the layered structure of the LSG and the morphology of the cracks,is proposed to investigate the strain sensing behavior and failure mechanism of the MRSS.Finally,due to the outstanding performance,the MRSS not only performes well in monitoring full-range human motions,but also achieves intelligent recognitions of various respiratory activities and ges-tures assisted by neural network algorithms(the accuracy up to 94.29%and 100%,respectively).This work provides a new approach for designing high-performance resistive strain sensors and shows great potential in full-range and long-term intelligent health management and human-machine interac-tions applications.

The effect of carbon nanotubes on osteogenic functions of adipose-derived mesenchymal stem cells in vitro and bone formation in vivo compared with that of nano-hydroxyapatite and the possible mechanism

It has been well recognized that the development and use of artificial materials with high osteogenic ability is one of the most promising means to replace bone grafting that has exhibited various negative effects.The biomimetic features and unique physiochemical properties of nanomaterials play important roles in stimulating cellular functions and guiding tissue regeneration.But efficacy degree of some nanomaterials to promote specific tissue formation is still not clear.We hereby comparatively studied the osteogenic ability of our treated multiwalled carbon nanotubes(MCNTs)and the main inorganic mineral component of natural bone,nano-hydroxyapatite(nHA)in the same system,and tried to tell the related mechanism.In vitro culture of human adiposederived mesenchymal stem cells(HASCs)on the MCNTs and nHA demonstrated that although there was no significant difference in the cell adhesion amount between on the MCNTs and nHA,the cell attachment strength and proliferation on the MCNTs were better.Most importantly,the MCNTs could induce osteogenic differentiation of the HASCs better than the nHA,the possible mechanism of which was found to be that the MCNTs could activate Notch involved signaling pathways by concentrating more proteins,including specific bone-inducing ones.Moreover,the MCNTs could induce ectopic bone formation in vivo while the nHA could not,which might be because MCNTs could stimulate inducible cells in tissues to form inductive bone better than nHA by concentrating more proteins including specific bone-inducing ones secreted from M2 macrophages.Therefore,MCNTs might be more effective materials for accelerating bone formation even than nHA.

Osteochondral scaffolds for early treatment of cartilage defects in osteoarthritic joints:from bench to clinic

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.

The physiological polyphosphate as a healing biomaterial for chronic wounds:Crucial roles of its antibacterial and unique metabolic energy supplying properties

Insufficient metabolic energy,in the form of adenosine triphosphate(ATP),and bacterial infections are among the main causes for the development of chronic wounds.Previously we showed that the physi-ological inorganic polymer polyphosphate(polyP)massively accelerates wound healing both in animals(diabetic mice)and,when incorporated into mats,in patients with chronic wounds.Here,we focused on a hydrogel-based gel formulation,supplemented with both soluble sodium polyP(Na-polyP)and amor-phous calcium polyP nanoparticles(Ca-polyP-NP).Exposure of human epidermal keratinocytes to the gel caused a significant increase in extracellular ATP level,an effect that was even enhanced when Na-polyP was combined with Ca-polyP-NP.Furthermore,it is shown that the added polyP in the gel is converted into a coacervate,leading to encapsulation and killing of bacteria.The data on human chronic wounds showed that the administration of hydrogel leads to the complete closure of these wounds.Histological analysis of biopsies showed an increased granulation of the wounds and an enhanced microvessel forma-tion.The results indicate that the polyP hydrogel,due to its properties to entrap bacteria and generate metabolic energy,is a very promising formulation for a new therapy for chronic wounds.