Promoting neurovascularized bone regeneration with a novel 3D printed inorganic-organic magnesium silicate/PLA composite scaffold.

Critical-size bone defect repair presents multiple challenges, such as osteogenesis, vascularization, and neurogenesis. Current biomaterials for bone repair need more consideration for the above functions. Organic-inorganic composites combined with bioactive ions offer significant advantages in bone regeneration. In our work, we prepared an organic-inorganic composite material by blending polylactic acid (PLA) with 3-aminopropyltriethoxysilane (APTES)-modified magnesium silicate (A-M2S) and fabricated it by 3D printing. With the increase of A-M2S proportion, the hydrophilicity and mineralization ability showed an enhanced trend, and the compressive strength and elastic modulus were increased from 15.29 MPa and 94.61 MPa to 44.30 MPa and 435.77 MPa, respectively. Furthermore, A-M2S/PLA scaffolds not only exhibited good cytocompatibility of bone marrow mesenchymal stem cells (BMSCs), human umbilical vein endothelial cells (HUVECs), and Schwann cells (SCs), but also effectively promoted osteogenesis, angiogenesis, and neurogenesis in vitro. After implanting 10 % A-M2S/PLA scaffolds in vivo, the scaffolds showed the most effective repair of cranium defects compared to the blank and control group (PLA). Additionally, they promoted the secretion of proteins related to bone regeneration and neurovascular formation. These results provided the basis for expanding the application of A-M2S and PLA in bone tissue engineering and presented a novel concept for neurovascularized bone repair.

Dexmedetomidine promotes the functional recovery of mice after acute ischemic stroke via activation of the α2-adrenoceptor.

Ischemic stroke (IS) is a well-known acute cerebrovascular disease characterized by high disability, morbidity, and recurrence rates with no effective treatments. Dexmedetomidine (DEX), a selective a2-adrenoceptor agonist used in anaesthesiology and pain management, has been found to exhibit neuroprotective effects in various diseases. However, its role in IS and the underlying mechanisms remains to be determined. Hence, the aim of the present study was to investigate the neuroprotective role of DEX in the recovery of mice following middle cerebral artery occlusion (MCAO). Mice were used to establish the animal model, and then DEX was injected. Behavioural tests (neurological function assessments, grip test, and rotarod test), brain water content measurement, ELISA, and measurement of oxidative stress were performed. DEX activated a2-adrenoceptor and resulted in reduced brain injury, as indicated by the decreased brain water content, S100 Calcium Binding Protein B (S100B) content, and neuron-specific enolase (NSE) content, whilst also inhibiting oxidative stress, as indicated by the increased total antioxidant capacity, catalase, glutathione, and superoxide dismutase levels, and decreased malondialdehyde and glutathione oxidized levels. Neuroinflammation was also reduced as indicated by the decrease in IFN-g, IL-1a, IL-1b, IL-6, TNF-a, and MMP levels, improved the recovery of neurological function, as indicated by the decreased neurological function score and mNSS, and increased grip strength and rotarod performance in MCAO mice. These combined results suggest that DEX may be a novel strategy for the treatment of IS.

Cell sheet-basedin vitrobone defect model for long term evaluation of bone repair materials.

Development of tissue-engineeredin vitrohuman bone defect models for evaluation of bone repair materials (BRMs) is a promising approach for addressing both translational and ethical concerns regarding animal models. In this study, human bone marrow mesenchymal stem cell sheets were stacked to form a periosteum like tissue. HE staining showed a cell-dense, multilayered structure. BRMs were implanted in the defect area of the three-dimensional (3D) model. The CCK-8 test demonstrated that the 3D model was stronger in resisting the cytotoxicity of three kinds of commercial BRMs than the 2D culture model, which was consistent within vivoresults. After 28 d implantation in the 3D model, western blot and RT-qPCR showed that three materials induced increased expressions of RUNX2, OSX, OCN, OPN, while Materials B and C seemed to have stronger osteoinductivity than A.In vivoexperiments also confirmed the osteoinductivity of the BRMs after 28 and 182 d implantation. Alizarin red staining proved that the mineralized nodules of Materials B and C were more than that of A. The differences of osteogenic properties among three BMRs might be attributed to calcium ion release. This cell sheet-based bone tissue model can resist cytotoxicity of BRMs, demonstrating the priority of long-term evaluation of osteoinductivity of BRMs. Further, the osteoinduction results of the 3D model corresponded to that ofin vivoexperiments, suggesting this model may have a potential to be used as a novel tool for rapid, accurate evaluation of BRMs, and thus shorten their research and development process.

Preparation of a 3D printable high-performance GelMA hydrogel loading with magnetic cobalt ferrite nanoparticles.

Osteosarcoma remains a worldwide concern due to the poor effectiveness of available therapies in the clinic. Therefore, it is necessary to find a safe and effective therapy to realize the complete resection of osteosarcoma and reconstruction of the bone defect. Magnetic hyperthermia based on magnetic nanoparticles can kill tumor cells by raising the temperature without causing the side effects of conventional cancer treatments. This research aims to design a high-performance magnetic hydrogel composed of gelatin methacrylate and highly magnetic cobalt ferrite (CFO) nanoparticles for osteosarcoma treatment. Specifically, CFO is surface functionalized with methacrylate groups (MeCFO). The surface modified CFO has good biocompatibility and stable solution dispersion ability. Afterward, MeCFO nanoparticles are incorporated into GelMA to fabricate a three-dimensional (3D) printable MeCFO/GelMA magnetic hydrogel and then photocross-linked by UV radiation. MeCFO/GelMA hydrogel has high porosity and swelling ability, indicating that the hydrogel possesses more space and good hydrophily for cell survival. The rheological results showed that the hydrogel has shear thinning property, which is suitable as a bioprinting ink to produce desired structures by a 3D printer. Furthermore, 50 µg/mL MeCFO not only decreases the cell activity of osteosarcoma cells but also promotes the osteogenic differentiation of mBMSCs. The results of the CCK-8 assay and live/dead staining showed that MeCFO/GelMA hydrogel had good cytocompatibility. These results indicated that MeCFO/GelMA hydrogel with potential antitumor and bone reconstruction functions is a promising therapeutic strategy after osteosarcoma resection.

A chitosan and hyaluronic acid-modified layer-by-layer lubrication coating for cardiovascular catheter.

Despite the fact that transcatheter cardiovascular interventions are increasingly prevalent nowadays, friction damage caused by mechanical interaction between blood vessel and cardiovascular catheter limit their therapeutic utility. Based on dopamine-modified hyaluronic (HA-DN) acid and chitosan (CHI), a layer-by-layer lubricating coating for cardiovascular catheters was designed and assessed in this work. Results showed that the CHI/HA-DN composite coatings became more hydrophilic as the deposition layers were increased. The (CHI/HA-DN)8 assembly effectively reduced the coefficient of friction (COF) and related frictional energy dissipation. Besides, the fluorescent intensity, number of nucleus, SEM morphology and histological slices after friction experiment demonstrated that the (CHI/HA-DN)8 coating can protect the aorta from mechanical injury related to the control group. In conclusion, the CHI/HA-DN assembly can provide an alternative selection for low-damage lubricating cardiovascular catheter.

Catechol-modified chitosan hydrogel containing PLGA microspheres loaded with triclosan and chlorhexidine: a sustained-release antibacterial system for urinary catheters.

Blockage and infection are common in hospitals, especially with long-term indwelling catheters, due to bacterial adhesion, colonization, and other reasons. A drug-sustained-release antibacterial coating for urinary catheters was described in this paper. Chlorhexidine (CHX) and triclosan (TCS) were encapsulated in poly(lactic-co-glycolic acid) microspheres and mixed with a modified chitosan hydrogel deposited on the surface of silicone rubber. The results showed that drugs can be released continuously more than 35 days. Catechol-modified chitosan (Chi-C) hydrogel was successful synthesized according to FT-IR and UV spectrophotometry, as well as 1H NMR. Furthermore, the coating with CHX and TCS presented stable antibacterial ability compared to the other groups. The results of CCK-8 revealed that the coating was cytotoxic-free and had a wide range of applications. The findings could provide a new drug sustained-release system and hydrogel-microsphere assembly for urinary catheters. HighlightsThe microspheres presented a sustained release more than 40 days with a remarkable initial burst release.The microspheres/catechol-modified chitosan (Chi-C)/silicon rubber system emerged stable binding ability in liquid environment more than 14 days.The Chi-C/chlorhexidine (CHX)+triclosan (TCS) microspheres system presented better antimicrobial property for entire experiment period.The coated samples showed no significant difference for relative growth rate (RGR) compared to different groups.