A 3D-Bioprinted dual growth factor-releasing intervertebral disc scaffold induces nucleus pulposus and annulus fibrosus reconstruction

Regeneration of Intervertebral disc(IVD)is a scientific challenge because of the complex structure and composition of tissue,as well as the difficulty in achieving bionic function.Here,an anatomically correct IVD scaffold composed of biomaterials,cells,and growth factors were fabricated via three-dimensional(3D)bioprinting technology.Connective tissue growth factor(CTGF)and transforming growth factor-β3(TGF-β3)were loaded onto polydopamine nanoparticles,which were mixed with bone marrow mesenchymal stem cells(BMSCs)for regenerating and simulating the structure and function of the nucleus pulposus and annular fibrosus.In vitro experiments confirmed that CTGF and TGF-β3 could be released from the IVD scaffold in a spatially controlled manner,and induced the corresponding BMSCs to differentiate into nucleus pulposus like cells and annulus fibrosus like cells.Next,the fabricated IVD scaffold was implanted into the dorsum subcutaneous of nude mice.The reconstructed IVD exhibited a zone-specific matrix that displayed the corresponding histological and immunological phenotypes:primarily type II collagen and glycosaminoglycan in the core zone,and type I collagen in the surrounding zone.The testing results demonstrated that it exhibited good biomechanical function of the reconstructed IVD.The results presented herein reveal the clinical application potential of the dual growth factors-releasing IVD scaffold fabricated via 3D bioprinting.However,the evaluation in large mammal animal models needs to be further studied.

Stem cell homing-based tissue engineering using bioactive materials

Tissue engineering focuses on repairing tissue and restoring tissue functions by employing three elements： scaffolds, cells and biochemical signals. In tissue engineering, bioactive material scaffolds have been used to cure tissue and organ defects with stem cell-based therapies being one of the best documented approaches. In the review, different biomaterials which are used in several methods to fabricate tissue engineering scaffolds were explained and show good properties （biocompatibility, biodegradability, and mechanical properties etc.） for cell migration and infiltration. Stem cell homing is a recruitment process for inducing the migration of the systemically transplanted cells, or host cells, to defect sites. The mechanisms and modes of stem cell homing-based tissue engineering can be divided into two types depending on the source of the stem cells： endogenous and exogenous. Exogenous stem cell-based bioactive scaffolds have the challenge of long-term culturing in vitro and for endogenous stem cells the biochemical signal homing recruitment mechanism is not clear yet. Although the stem cell homing-based bioactive scaffolds are attractive candidates for tissue defect therapies, based on in vitro studies and animal tests, there is still a long way before clinical application.

High-precision,gelatin-based,hybrid,bilayer scaffolds using melt electro-writing to repair cartilage injury

Articular cartilage injury is a common disease in the field of orthopedics.Because cartilage has poor self-repairing ability,medical intervention is needed.Using melt electro-writing(MEW)technology,tissue engineering scaffolds with high porosity and high precision can be prepared.However,ordinary materials,especially natural polymer materials,are difficult to print.In this study,gelatin was mixed with poly(lactic-co-glycolic acid)to prepare high-concentration and high-viscosity printer ink,which had good printability and formability.A composite scaffold with full-layer TGF-β1 loading mixed with hydroxyapatite was prepared,and the scaffold was implanted at the cartilage injury site;microfracture surgery was conducted to induce the mesenchyme in the bone marrow.Quality stem cells thereby promoted the repair of damaged cartilage.In summary,this study developed a novel printing method,explored the molding conditions based on MEW printing ink,and constructed a bioactive cartilage repair scaffold.The scaffold can use autologous bone marrow mesenchymal stem cells and induce their differentiation to promote cartilage repair.

Clemastine rescues behavioral changes and enhances remyelination in the cuprizone mouse model of demyelination

Increasing evidence suggests that white matter disorders based on myelin sheath impairment may underlie the neuropathological changes in schizophrenia.But it is unknown whether enhancing remyelination is a beneficial approach to schizophrenia.To investigate this hypothesis,we used clemastine,an FDA-approved drug with high potency in promoting oligodendroglial differentiation and myelination,on a cuprizone-induced mouse model of demyelination.The mice exposed to cuprizone（0.2%in chow） for 6 weeks displayed schizophrenia-like behavioral changes,including decreased exploration of the center in the open field test and increased entries into the arms of the Y-maze,as well as evident demyelination in the cortex and corpus callosum.Clemastine treatment was initiated upon cuprizone withdrawal at 10 mg/kg per day for3 weeks.As expected,myelin repair was greatly enhanced in the demyelinated regions with increased mature oligodendrocytes（APC-positive） and myelin basic protein.More importantly,the clemastine treatment rescued the schizophrenia-like behavioral changes in the open field test and the Y-maze compared to vehicle,suggesting a beneficial effect via promoting myelin repair.Our findings indicate that enhancing remyelination may be a potential therapy for schizophrenia.

Fabrication and characterization of Antheraea pernyi silk fibroin-blended P（LLA-CL） nanofibrous scaffolds for peripheral nerve tissue engineering

Electrospun nanofibers have gained widespreading interest for tissue engineering application. In the present study, ApF/P（LLA-CL） nanofibrous scaffolds were fabricated via electrospinning. The feasibility of the material as tissue engineering nerve scaffold was investigated in vitro. The average diameter increased with decreasing the blend ratio of ApF to P（LLA-CL）. Characterization of 13C NMR and FTIR clarified that there is no obvious chemical bond reaction between ApF and P（LLA-CL）. The tensile strength and elongation at break increased with the content increase of P（LLA-CL）. The surface hydrophilic property of nanofibrous scaffolds enhanced with the increased content of ApF. Cell viability studies with Schwann cells demonstrated that ApFIP（LLA-CL） blended nanofibrous scaffolds significantly promoted cell growth as compare to P（LLA-CL）, especially when the weight ratio of ApF to P（LLA-CL） was 25：75. The present work provides a basis for further studies of this novel nanofibrous material （ApF/P（LLA-CL）） in peripheral nerve tissue repair or regeneration.