l-Theanine and NEP1-40 promote nerve regeneration and functional recovery after brachial plexus root avulsion.

Brachial plexus root avulsion causes severe sequelae Treatments and prognosis face many problems, including inflammatory reaction, oxidative damage, and myelin related inhibitory effect. l-Theanine has anti-inflammatory, anti-oxidative, and neuroprotective effects. NEP1-40 competitively inhibits Nogo-66 receptor (NgR1) promotes axonal regeneration. Forty-eight Sprague-Dawley rats were randomly assigned into four groups to establish an animal model of brachial plexus root avulsion. Inflammation and oxidative damage were evaluated by spectrophotometry and motor function of the upper limbs was assessed via Terzis grooming test after modeling. Immunofluorescence and hematoxylin and eosin staining were utilized to determine the content of reactive oxygen species, activation of microglial cells, neuroprotection, and nerve regeneration. Compared with the control group, the L-Theanine + NEP1-40 group had significantly decreased myeloperoxidase, malondialdehyde, interleukin-6, reactive oxygen species, and microglial cells, significantly increased score on the Terzis grooming test, increased motor neuron content, and thickened muscle fibers, increased area, and appearance of large and clear motor endplate structures. The results of this study suggest that l-Theanine combined with NEP1-40significantly promoted nerve regeneration after brachial plexus root avulsion, and may be a potential treatment for promoting nerve regeneration. Possible mechanisms underlying these results are alleviation of oxidative damage and inflammatory responses in the injured area and antagonism of myelin inhibition.

Intramuscular Injection of Adenoassociated Virus Encoding Human Neurotrophic Factor 3 and Exercise Intervention Contribute to Reduce Spasms after Spinal Cord Injury.

Limb spasms are phenomena of hyperreflexia that occur after spinal cord injury. Currently, the clinical treatment is less than ideal. Our goal is to develop a combination therapy based on individualized medicine to reduce spasticity after spinal cord injury. In this study, rats received a severe contusive injury at the T9 segment of the spinal cord, followed by gene therapy with adenoassociated virus encoding human neurotrophic factor 3 (AAV-NT3) and a 2-week exercise program starting at 4 weeks after injury. We quantified the frequency of spasms during a swimming test at 4 and 6 weeks after injury and confirmed the results of the swimming test by measuring the H-reflex of the plantar muscle. We obtained weekly hind limb exercise scores to assess the effect of the interventions in hind limb motor function improvement. Then, we used immunofluorescence to observe the immunoreactivity of spinal motor neurons, synaptophysin, cholinergic interneurons, and GABAergic interneurons. We also measured the expression of KCC2 in the spinal cord by western blot. We found that AAV-NT3 gene therapy, exercise, and combination therapy all attenuated the frequency of spasms in the swimming test conducted at 6 weeks after spinal cord injury and increased rate-dependent depression of H-reflex. Combination therapy was significantly superior to AAV-NT3 alone in protecting motor neurons. Recovery of KCC2 expression was significantly greater in rats treated with combination therapy than in the exercise group. Combination therapy was also significantly superior to individual therapies in remodeling spinal cord neurons. Our study shows that the combination of AAV-NT3 gene therapy and exercise can alleviate muscle spasm after spinal cord injury by altering the excitability of spinal interneurons and motor neurons. However, combination therapy did not show a significant additive effect, which needs to be improved by adjusting the combined strategy.

MicroRNA-190b inhibits tumor cell proliferation and induces apoptosis by regulating Bcl-2 in U2OS osteosarcoma cells.

Osteosarcoma (OS) is one of the most prevalent malignancies in bone with no established therapy so far. This study was aimed to clarify the role of miR-190b in tumor cell growth of OS. The miR-190b mimic, inhibitor and miR-control were transfected into human OS U2OS cells. Then U2OS cell proliferation was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and bromodeoxyuridine (BrdU) incorporation assay. The apoptotic U2OS cells were detected by flow cytometry. Additionally, cell-cycle regulators p27, p21 and apoptosis factors B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X (Bax), caspase-3 were examined by western blotting. Overexpressing miR-190b observably reduced cell viability, BrdU-positive cells (both P < 0.05) and caused strong accumulation of cell-cycle inhibitor p27 in U2OS cells compared with the miR-control, whereas the miR-190b inhibitor exerted opposite effects. Further, a marked increase of 18% rate of apoptotic cells by the overexpressing miR-190b (P < 0.01) and 4% decrease by miR-190b inhibitor (P < 0.05) were detected. The protein expressions of Bcl-2 were downregulated, Bax, pro-caspase-3 and active caspase-3 were upregulated by overexpressing miR-190b in U2OS cell line, while miR-190b inhibitor achieved opposite effects. The present study demonstrates that miR-190b inhibits tumor cell proliferation and induces apoptosis by regulating Bcl-2 in U2OS cells, which points to miR-190b as a novel oncosuppressor for OS. The identified tumor suppressive capacity of miR-190b provides novel avenues for achieving better OS therapy.

Distribution of selenium and cadmium in soil-rice system of selenium-rich area in Hainan, China.

Rice, which is the staple food in East Asia, is a source of Selenium (Se) and Cadmium (Cd). The distribution of Se and Cd in soil-rice system is significant to human nutrition and public health. This study is to explore the distribution of Se and Cd in arable land soils and their distribution in polished rice and stalks of Se-rich area. A total of 63 soil samples and 126 rice samples (63 groups of rice grains and stalk samples) were collected from West Hainan Island to determine Se and Cd concentrations. The results suggested the concentration of Se in soil was higher than average level in China, and Cd content was lower than the agricultural land-use threshold of China. The distribution of Se and Cd in arable land soil was primarily determined by diagenesis and mineralization. Se and Cd were more inclined to accumulate in stalks than rice grains, and the contents in polished rice were correlated with that in stalk. Acidification of arable land soil will threaten human nutrition and health for the bioaccumulation factor of Se in polished rice decreased significantly with the decrease of soil pH, while that of Cd in polished rice increased significantly. Therefore, application of lime or alkaline fertilizers in arable land soil of Se-rich area can promote the accumulation of Se in polished rice but reduced the intake of Cd in rice crops.

Injectable Hydrogel Loaded with CDs and FTY720 Combined with Neural Stem Cells for the Treatment of Spinal Cord Injury.

Purpose: Spinal cord injury (SCI) is an incurable and disabling event that is accompanied by complex inflammation-related pathological processes, such as the production of excessive reactive oxygen species (ROS) by infiltrating inflammatory immune cells and their release into the extracellular microenvironment, resulting in extensive apoptosis of endogenous neural stem cells. In this study, we noticed the neuroregeneration-promoting effect as well as the ability of the innovative treatment method of FTY720-CDs@GelMA paired with NSCs to increase motor function recovery in a rat spinal cord injury model. Methods: Carbon dots (CDs) and fingolimod (FTY720) were added to a hydrogel created by chemical cross-linking GelMA (FTY720-CDs@GelMA). The basic properties of FTY720-CDs@GelMA hydrogels were investigated using TEM, SEM, XPS, and FTIR. The swelling and degradation rates of FTY720-CDs@GelMA hydrogels were measured, and each group's ability to scavenge reactive oxygen species was investigated. The in vitro biocompatibility of FTY720-CDs@GelMA hydrogels was assessed using neural stem cells. The regeneration of the spinal cord and recovery of motor function in rats were studied following co-treatment of spinal cord injury using FTY720-CDs@GelMA hydrogel in combination with NSCs, utilising rats with spinal cord injuries as a model. Histological and immunofluorescence labelling were used to determine the regeneration of axons and neurons. The recovery of motor function in rats was assessed using the BBB score. Results: The hydrogel boosted neurogenesis and axonal regeneration by eliminating excess ROS and restoring the regenerative environment. The hydrogel efficiently contained brain stem cells and demonstrated strong neuroprotective effects in vivo by lowering endogenous ROS generation and mitigating ROS-mediated oxidative stress. In a follow-up investigation, we discovered that FTY720-CDs@GelMA hydrogel could dramatically boost NSC proliferation while also promoting neuronal regeneration and synaptic formation, hence lowering cavity area. Conclusion: Our findings suggest that the innovative treatment of FTY720-CDs@GelMA paired with NSCs can effectively improve functional recovery in SCI patients, making it a promising therapeutic alternative for SCI.

Applications of MXene and its modified materials in skin wound repair.

The rapid healing and repair of skin wounds has been receiving much clinical attention. Covering the wound with wound dressing to promote wound healing is currently the main treatment for skin wound repair. However, the performance of wound dressing prepared by a single material is limited and cannot meet the requirements of complex conditions for wound healing. MXene is a new two-dimensional material with electrical conductivity, antibacterial and photothermal properties and other physical and biological properties, which has a wide range of applications in the field of biomedicine. Based on the pathophysiological process of wound healing and the properties of ideal wound dressing, this review will introduce the preparation and modification methods of MXene, systematically summarize and review the application status and mechanism of MXene in skin wound healing, and provide guidance for subsequent researchers to further apply MXene in the design of skin wound dressing.

An injectable, self-healing, electroconductive hydrogel loaded with neural stem cells and donepezil for enhancing local therapy effect of spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is a serious injury with high mortality and disability rates, and there is no effective treatment at present. It has been reported that some treatments, such as drug intervention and stem cell transplantation have positive effects in promoting neurological recovery. Although those treatments are effective for nerve regeneration, many drawbacks, such as low stem cell survival rates and side effects caused by systemic medication, have limited their development. In recent years, injectable hydrogel materials have been widely used in tissue engineering due to their good biocompatibility, biodegradability, controllable properties, and low invasiveness. The treatment strategy of injectable hydrogels combined with stem cells or drugs has made some progress in SCI repair, showing the potential to overcome the drawbacks of traditional drugs and stem cell therapy. METHODS: In this study, a novel injectable electroactive hydrogel (NGP) based on sodium hyaluronate oxide (SAO) and polyaniline-grafted gelatine (NH2-Gel-PANI) was developed as a material in which to load neural stem cells (NSCs) and donepezil (DPL) to facilitate nerve regeneration after SCI. To evaluate the potential of the prepared NGP hydrogel in SCI repair applications, the surface morphology, self-repairing properties, electrical conductivity and cytocompatibility of the resulting hydrogel were analysed. Meanwhile, we evaluated the neural repair ability of NGP hydrogels loaded with DPL and NSCs using a rat model of spinal cord injury. RESULTS: The NGP hydrogel has a suitable pore size, good biocompatibility, excellent conductivity, and injectable and self-repairing properties, and its degradation rate matches the repair cycle of spinal cord injury. In addition, DPL could be released continuously and slowly from the NGP hydrogel; thus, the NGP hydrogel could serve as an excellent carrier for drugs and cells. The results of in vitro cell experiments showed that the NGP hydrogel had good cytocompatibility and could significantly promote the neuronal differentiation and axon growth of NSCs, and loading the hydrogel with DPL could significantly enhance this effect. More importantly, the NGP hydrogel loaded with DPL showed a significant inhibitory effect on astrocytic differentiation of NSCs in vitro. Animal experiments showed that the combination of NGP hydrogel, DPL, and NSCs had the best therapeutic effect on the recovery of motor function and nerve conduction function in rats. NGP hydrogel loaded with NSCs and DPL not only significantly increased the myelin sheath area, number of new neurons and axon area but also minimized the area of the cystic cavity and glial scar and promoted neural circuit reconstruction. CONCLUSIONS: The DPL- and NSC-laden electroactive hydrogel developed in this study is an ideal biomaterial for the treatment of traumatic spinal cord injury.

Advances in the application of Mxene nanoparticles in wound healing.

Skin is the largest organ of the human body. It plays a vital role as the body's first barrier: stopping chemical, radiological damage and microbial invasion. The importance of skin to the human body can never be overstated. Delayed wound healing after a skin injury has become a huge challenge in healthcare. In some situations, this can have very serious and even life-threatening effects on people's health. Various wound dressings have been developed to promote quicker wound healing, including hydrogels, gelatin sponges, films, and bandages, all work to prevent the invasion of microbial pathogens. Some of them are also packed with bioactive agents, such as antibiotics, nanoparticles, and growth factors, that help to improve the performance of the dressing it is added to. Recently, bioactive nanoparticles as the bioactive agent have become widely used in wound dressings. Among these, functional inorganic nanoparticles are favored due to their ability to effectively improve the tissue-repairing properties of biomaterials. MXene nanoparticles have attracted the interest of scholars due to their unique properties of electrical conductivity, hydrophilicity, antibacterial properties, and biocompatibility. The potential for its application is very promising as an effective functional component of wound dressings. In this paper, we will review MXene nanoparticles in skin injury repair, particularly its synthesis method, functional properties, biocompatibility, and application.

Advances in Conductive Hydrogel for Spinal Cord Injury Repair and Regeneration.

Spinal cord injury (SCI) treatment represents a major challenge in clinical practice. In recent years, the rapid development of neural tissue engineering technology has provided a new therapeutic approach for spinal cord injury repair. Implanting functionalized electroconductive hydrogels (ECH) in the injury area has been shown to promote axonal regeneration and facilitate the generation of neuronal circuits by reshaping the microenvironment of SCI. ECH not only facilitate intercellular electrical signaling but, when combined with electrical stimulation, enable the transmission of electrical signals to electroactive tissue and activate bioelectric signaling pathways, thereby promoting neural tissue repair. Therefore, the implantation of ECH into damaged tissues can effectively restore physiological functions related to electrical conduction. This article focuses on the dynamic pathophysiological changes in the SCI microenvironment and discusses the mechanisms of electrical stimulation/signal in the process of SCI repair. By examining electrical activity during nerve repair, we provide insights into the mechanisms behind electrical stimulation and signaling during SCI repair. We classify conductive biomaterials, and offer an overview of the current applications and research progress of conductive hydrogels in spinal cord repair and regeneration, aiming to provide a reference for future explorations and developments in spinal cord regeneration strategies.

Significant loss of soil inorganic carbon at the continental scale.

Widespread soil acidification due to atmospheric acid deposition and agricultural fertilization may greatly accelerate soil carbonate dissolution and CO2 release. However, to date, few studies have addressed these processes. Here, we use meta-analysis and nationwide-survey datasets to investigate changes in soil inorganic carbon (SIC) stocks in China. We observe an overall decrease in SIC stocks in topsoil (0-30 cm) (11.33 g C m-2 yr-1) from the 1980s to the 2010s. Total SIC stocks have decreased by ∼8.99 ± 2.24% (1.37 ± 0.37 Pg C). The average SIC losses across China (0.046 Pg C yr-1) and in cropland (0.016 Pg C yr-1) account for ∼17.6%-24.0% of the terrestrial C sink and 57.1% of the soil organic carbon sink in cropland, respectively. Nitrogen deposition and climate change have profound influences on SIC cycling. We estimate that ∼19.12%-19.47% of SIC stocks will be further lost by 2100. The consumption of SIC may offset a large portion of global efforts aimed at ecosystem carbon sequestration, which emphasizes the importance of achieving a better understanding of the indirect coupling mechanisms of nitrogen and carbon cycling and of effective countermeasures to minimize SIC loss.

Enhanced wound repair ability of arginine-chitosan nanocomposite membrane through the antimicrobial peptides-loaded polydopamine-modified graphene oxide.

Skin wound healing is a complicated and lengthy process, which is influenced by multiple factors and need a suitable cellular micro-environment. For skin wound, wound dressings remain a cornerstone of dermatologic therapy at present. The dressing material can create an effective protective environment for the wound, and the interactions between the dressing and the wound has a great impact on the wound healing efficiency. An ideal wound dressing materials should have good biocompatibility, moisturizing property, antibacterial property and mechanical strength, and can effectively prevent wound infection and promote wound healing. In this study, in order to design wound dressing materials endowed with excellent antibacterial and tissue repair properties, we attempted to load antimicrobial peptides onto dopmine-modified graphene oxide (PDA@GO) using lysozyme (ly) as a model drug. Then, functionalized GO was used to the surface modification of arginine-modified chitosan (CS-Arg) membrane. To evaluate the potential of the prepared nanocomposite membrane in wound dressing application, the surface morphology, hydrophilic, mechanical properties, antimicrobial activity, and cytocompatibility of the resulting nanocomposite membrane were analyzed. The results revealed that prepared nanocomposite membrane exhibited excellent hydrophilic, mechanical strength and antimicrobial activity, which can effectively promote cell growth and adhesion. In particular, using PDA@GO as drug carrier can effectively maintain the activity of antimicrobial peptides, and can maximize the antibacterial properties of the nanocomposite membrane. Finally, we used rat full-thickness wound models to observe wound healing, and the surface interactions between the prepared nanocomposite membrane and the wound. The results indicated that nanocomposite membrane can obviously accelerated wound closure, and the wounds showed reduced inflammation, improved angiogenesis and accelerated re-epithelialization. Therefore, incorporation of antimicrobial peptides-functionalize graphene oxide (ly-PDA@GO) into CS-Arg membrane was a viable strategy for fabricating excellent wound dressing. Together, this study not only prepared a wound dressing with excellent tissue repair ability, but also provided a novel idea for the development of graphene oxide-based antibacterial dressing.

Dual bio-active factors with adhesion function modified electrospun fibrous scaffold for skin wound and infections therapeutics.

Electrospun fibrous scaffolds combined with bioactive factors can display impressive performance as an ideal wound dressing, since they can mimic the composition and physicochemical properties of the extracellular matrix (ECM). The aim of this study was to fabricate a new composite biomaterial (IGF1-DA and Os-DA-modified PLGA electrospun fibrous scaffold) for wound healing, using a rat model for experimental evaluation. A small pentapeptide tag composed of DA-Lys-DA-Lys-DA residues was introduced into insulin-like growth factor 1 (IGF1) and the antimicrobial peptide Os to prepare IGF1 and Os modified with 3,4-dihydroxyphenylalanine (DA) (IGF1-DA and Os-DA). The designed chimeric growth factor and antimicrobial peptide could successfully anchor to PLGA electrospun fibrous scaffolds, and the growth factor and antimicrobial peptide could be controllably released from the electrospun fibrous scaffolds. The results showed that the IGF1-DA and Os-DA-modified PLGA electrospun fibrous scaffolds (PLGA/Os-DA/IGF1-DA) exhibited high hydrophilicity and antimicrobial activity; moreover, the porous network of the scaffolds was similar to that of the natural ECM, which can provide a favourable environment for BALB/C 3T3 cells growth. The in vivo application of PLGA/Os-DA/IGF1-DA electrospun fibrous scaffolds in rat skin wounds resulted in improved wound recovery and tissue regeneration rate. The experimental results indicated that the IGF1-DA and Os-DA could effectively bind to PLGA electrospun fibrous scaffolds, promote wound healing and prevent infection in rats, thereby suggesting that PLGA/Os-DA/IGF1-DA electrospun fibrous scaffolds have a wide application value in the field of skin wound repair.

Localised delivery of quercetin by thermo-sensitive PLGA-PEG-PLGA hydrogels for the treatment of brachial plexus avulsion.

Accumulating evidence indicates that oxidative stress and inflammation are implicated in brachial plexus avulsion (BPA). Quercetin has anti-inflammatory, anti-oxidant, anti-apoptotic, and neuroprotective properties. This study investigated the therapeutic efficacy of a temperature-sensitive poly(D,L-lactide-co-glycolide)-poly(ethylene-glycol)-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) hydrogel sustained-release system of quercetin in BPA. In situ injections of the hydrogel loaded with different concentrations of quercetin were conducted in a rat model of BPA. Significantly reduced reactive oxygen species and interleukin-6 levels in the injured spinal cord 24 h post-surgery, increased number of anterior horn motor and functional neurons in the spinal cord 6 weeks post-surgery, thickened biceps muscle fibres and enlarged endplate area with clear structure, reduced demyelinated peripheral nerves, and significantly increased Terzis grooming test scores were found in the groups with 50 or 100 mg/mL quercetin-loaded hydrogels compared with the control and blank hydrogel groups. In conclusion, the temperature-sensitive quercetin loaded PLGA-PEG-PLGA hydrogel sustained-release system can alleviate oxidative damage and inflammation in the spinal cord, increase neuron survival rate, and promote nerve regeneration and motor function recovery in rats with early BPA. The findings suggest that this drug-loaded hydrogel has potential applications in the clinical treatment of BPA.

Preparation, characterization and evaluation of a new film based on chitosan, arginine and gold nanoparticle derivatives for wound-healing efficacy.

It is well-known that the combination of polymers and nanoparticles (NPs) provides optimised wound dressing and accelerates wound healing. The knowledge about the structure and properties of these materials is of critical importance in biological processes related to wound healing. In this study, we prepared a chitosan (CS) film modified with arginine (Arg) and gold NPs (AuNPs) and investigated its effectiveness as a dressing material for wound healing. Fourier-transform infrared spectroscopy (FTIR) confirmed that Arg was successfully grafted on CS. The resultant CS-Arg/AuNP film was then characterised by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The modification of Arg and AuNPs improved the hydrophilicity, mechanical strength and antibacterial properties of the film, which in turn provided an enhanced ideal environment for cell adhesion and proliferation. Cell Counting Kit-8 (CCK-8) was used to demonstrate the survival rate. Furthermore, the proteins involved in wound healing were evaluated qualitatively and quantitatively by immunofluorescence and western blotting, respectively. The skin defect models used for the in vivo studies revealed that the CS-Arg/AuNP dressing accelerated wound closure, re-epithelialization and collagen deposition. Our cumulative findings support the feasibility of using the proposed film as a promising candidate for tissue engineering of the skin in the near future.

Application of fibrin-based hydrogels for nerve protection and regeneration after spinal cord injury.

Traffic accidents, falls, and many other events may cause traumatic spinal cord injuries (SCIs), resulting in nerve cells and extracellular matrix loss in the spinal cord, along with blood loss, inflammation, oxidative stress (OS), and others. The continuous development of neural tissue engineering has attracted increasing attention on the application of fibrin hydrogels in repairing SCIs. Except for excellent biocompatibility, flexibility, and plasticity, fibrin, a component of extracellular matrix (ECM), can be equipped with cells, ECM protein, and various growth factors to promote damage repair. This review will focus on the advantages and disadvantages of fibrin hydrogels from different sources, as well as the various modifications for internal topographical guidance during the polymerization. From the perspective of further improvement of cell function before and after the delivery of stem cell, cytokine, and drug, this review will also evaluate the application of fibrin hydrogels as a carrier to the therapy of nerve repair and regeneration, to mirror the recent development tendency and challenge.

Advances in the application of gold nanoparticles in bone tissue engineering.

The materials used in bone tissue engineering (BTE) have been advancing with each passing day. With the continuous development of nanomedicine, gold nanoparticles (GNPs), which are easy to be synthesized and functionalized, have attracted increasing attention. Recent years have witnessed this amazing material, i.e., GNPs characterized with large surface area to volume ratio, biocompatibility, medical imaging property, hypotoxicity, translocation into the cells, high reactivity, and other properties, perform distinct functions in BTE. However, the low stability of GNPs in the biotic environment makes them in the requirements of modification or recombination before being used. After being combined with the advantages of other materials, the structures of GNPs have exhibited great potential in stem cells, scaffolds, delivery systems, medical imaging, and other aspects. This review will focus on the advances in the application of GNPs after modification or recombination with other materials to BTE.

The Advances of Ceria Nanoparticles for Biomedical Applications in Orthopaedics.

The ongoing biomedical nanotechnology has intrigued increasingly intense interests in cerium oxide nanoparticles, ceria nanoparticles or nano-ceria (CeO2-NPs). Their remarkable vacancy-oxygen defect (VO) facilitates the redox process and catalytic activity. The verification has illustrated that CeO2-NPs, a nanozyme based on inorganic nanoparticles, can achieve the anti-inflammatory effect, cancer resistance, and angiogenesis. Also, they can well complement other materials in tissue engineering (TE). Pertinent to the properties of CeO2-NPs and the pragmatic biosynthesis methods, this review will emphasize the recent application of CeO2-NPs to orthopedic biomedicine, in particular, the bone tissue engineering (BTE). The presentation, assessment, and outlook of the orthopedic potential and shortcomings of CeO2-NPs in this review expect to provide reference values for the future research and development of therapeutic agents based on CeO2-NPs.

BMP-2-releasing gelatin microspheres/PLGA scaffolds for bone repairment of X-ray-radiated rabbit radius defects.

The purpose of this research is to assess the feasibility of poly(lactic-co-glycolic) acid (PLGA) incorporating gelatin microspheres (PLGA/GMs scaffold) for enhancing osteogenesis in vitro and at a radius defect of rabbits after X-ray radiation in vivo. After incorporating gelatin microspheres, PLGA scaffold demonstrated improved mechanical properties. Moreover, a sustained release property of recombinant human bone morphogenetic protein-2 (BMP-2) was achieved in BMP-2-releasing PLGA/GMs scaffold. BMP-2-releasing PLGA/GMs scaffold also enhanced proliferation and osteogenesis of rabbit bone mesenchymal stem cells (BMSCs) in vitro, indicating the bioactivity of BMP-2. After finishing X-ray radiation of the radius bone, 20-mm radius bone defects were generated, followed by being implanted with BMP-2-releasing PLGA/GMs scaffolds with or without bone marrow. Both PLGA/GMs scaffolds containing bone marrow or BMP-2 showed more obvious enhancement for bone regeneration than the empty scaffolds (control) at the radius defect. In the X-ray radiated groups, however, the bone regeneration was inhibited either with bone marrow or BMP-2. When combined with bone marrow, the BMP-2 showed significantly high osteogenic effect, regardless of X-ray radiation. It is considered that it is a promising way to repair bone defects even after X-ray radiation by a combination of bone marrow with the BMP-2-releasing PLGA/GMs scaffold.

Effect of electrical stimulation combined with graphene-oxide-based membranes on neural stem cell proliferation and differentiation.

The combination of composite nerve materials prepared using degradable polymer materials with biological or physical factors has received extensive attention as a means to treat nerve injuries. This study focused on the potential application of graphene oxide (GO) composite conductive materials combined with electrical stimulation (ES) in nerve repair. A conductive poly(L-lactic-co-glycolic acid) (PLGA)/GO composite membrane was prepared, and its properties were tested using a scanning electron microscope (SEM), a contact angle meter, and a mechanical tester. Next, neural stem cells (NSCs) were planted on the PLGA/GO conductive composite membrane and ES was applied. NSC proliferation and differentiation and neurite elongation were observed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, immunofluorescence, and PCR, respectively. The results showed that the PLGA/GO membrane had good hydrophilicity, mechanical strength, and protein adsorption. ES combined with the PLGA/GO membrane significantly promoted NSC proliferation and neuronal differentiation on the material surface and promoted significant neurite elongation. Our results suggest that ES combined with GO-related conductive composite materials can be used as a new therapeutic combination to treat nerve injuries.

Graphene oxide-PLGA hybrid nanofibres for the local delivery of IGF-1 and BDNF in spinal cord repair.

Spinal cord injury (SCI) can lead to permanent and severe functional impairment below the lesion level and is still one of the most challenging clinical problems. The treatment of SCI has progressed with the development of tissue engineering techniques. Insulin-like growth factor 1 (IGF-1) and brain-derived neurotrophic factor (BDNF) are growth factors closely related to nerve regeneration. In this study, IGF-1 and BDNF were successfully immobilized on biodegradable graphene oxide (GO)-incorporated PLGA (PLGA/GO) electrospun nanofibres. The effect of PLGA/GO nanofibres with immobilized IGF-1 and BDNF on neurogenesis was investigated in vitro and in vivo utilizing MTT assays, immunofluorescence, motor function detection and histology observations. We demonstrated that PLGA/GO nanofibres loaded with IGF-1 and BDNF not only protected NSCs from oxidative stress induced by H2O2 but also enhanced NSC proliferation and neuronal differentiation in vitro. The in vivo study of an SCI animal model demonstrated that local delivery of IGF-1 and BDNF immobilized to PLGA/GO nanofibres significantly improved functional locomotor recovery, reduced cavity formation and increased the number of neurons at the injury site. Our study indicated that PLGA/GO is an effective carrier for IGF-1 and BDNF delivery and that immobilization of IGF-1 and BDNF onto PLGA/GO nanofibres has a great potential as a nerve implant for spinal cord injury applications.