RESUMO
The urgent concerns of controlling water body eutrophication and the alleviating phosphorus shortage have led to an urgent need for action. The removal of phosphate from polluted waters and its reuse are essential for the prevention of eutrophication and for the sustainable utilization of phosphate resources. In this study, modified attapulgite with different Ca:Mg molar ratios was synthesized to facilitate the recovery of phosphate, with subsequent use of soil fertilizer. Ca-Mg modified attapulgite with the optimal ratio (ACM-5:3) exhibited an exceptional adsorption quality, achieving a maximum adsorption capacity of 63.2 mg/g. The pseudo-second-order model and Langmuir model could well describe the adsorption kinetics and isotherms, respectively. The adsorption mechanism analyses suggested that the interaction between ACM-5:3 and phosphate depended mainly on ion exchange and electrostatic attraction. Moreover, phosphate-laden-ACM-5:3 demonstrated a significant potential as a phosphorus-releasing fertilizer. It could promote corn growth by ensuring a continuous supply of phosphorus and minimizing phosphorus runoff losses. The above results suggested that ACM-5:3 was a potential adsorbent for efficient phosphate removal and recovery.
Assuntos
Fosfatos , Compostos de Silício , Poluentes Químicos da Água , Fertilizantes , Compostos de Magnésio , Fósforo , Adsorção , Cinética , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: Ischemic stroke is a leading cause of death and disability worldwide. However, the time window for quickly dissolving clots and restoring cerebral blood flow, using tissue-type plasminogen activator treatment is rather limited, resulting in many patients experiencing long-term functional impairments if not death. This study aims to determine the roles of cranial bone transport (CBT), a novel, effective, and simple surgical technique, in the recovery of ischemic stroke using middle cerebral artery occlusion (MCAO) rat model. METHODS: CBT was performed by slowly sliding a bone segment in skull with a special frame and a speed of 0.25 mm/12 hours for 10 days following MCAO. Morris water maze, rotarod test, and catwalk gait analysis were used to study the neurological behaviors, and infarct area and cerebral flow were evaluated during CBT process. Immunofluorescence staining of CD31 and Nestin/Sox2 (sex determining region Y box 2) was performed to study the angiogenesis and neurogenesis. OVA-A647 (ovalbumin-Alexa Fluor 647) was intracisterna magna injected to evaluate the meningeal lymphatic drainage function. RESULTS: CBT treatment has significantly reduced the ischemic lesions areas and improved the neurological deficits in MCAO rats compared with the rats in the control groups. CBT treatment significantly promoted angiogenesis and neurogenesis in the brain of MCAO rats. The drainage function of meningeal lymphatic vessels in MCAO rats was significantly impaired compared with normal rats. Ablation of meningeal lymphatic drainage led to increased neuroinflammation and aggravated neurological deficits and ischemic injury in MCAO rats. CBT treatment significantly improved the meningeal lymphatic drainage function and alleviated T-cell infiltration in MCAO rats. CONCLUSIONS: This study provided evidence for the possible mechanisms on how CBT attenuates ischemic stroke injury and facilitates rapid neuronal function recovery, suggesting that CBT may be an alternative treatment strategy for managing ischemic stroke.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Animais , Isquemia Encefálica/terapia , Modelos Animais de Doenças , Humanos , Infarto da Artéria Cerebral Média/patologia , Neovascularização Patológica , Neurogênese , Ratos , Crânio/patologiaRESUMO
The recombinant basic fibroblast growth factor (bFGF) containing collagen-binding domain (CBD) has been found to be a potential therapeutic factor in tissue regeneration. However, its binding efficiency and quantification remain uncertain. In this research, massive recombinant bFGFs with good bioactivity for enhancing the proliferation of NIH-3T3 cells were achieved. An ELISA-based quantitative method was set up to investigate the binding efficiency of CBD-bFGFs on collagen films. It indicated that the CBDs significantly increased the collagen-binding ability of bFGF (P < .05), with the optimum binding condition first determined to be in the pH range of 7.5-9.5 (P < .05). Then, the relevant equations to calculate the binding density of bFGF, C-bFGF, and V-bFGF were acquired. Analysis confirmed that the bioactivity of immobilized bFGFs was well correlated with the density of growth factor on collagen films. Based on this research, the density of growth factor is a logical and applicable dosage unit for quantification of binding efficiency of growth factors, rather than traditional concentration of soluble growth factors in tissue engineering applications.
Assuntos
Proliferação de Células , Colágeno Tipo I/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Animais , Ensaio de Imunoadsorção Enzimática , Fator 2 de Crescimento de Fibroblastos/química , Concentração de Íons de Hidrogênio , Camundongos , Células NIH 3T3 , Ligação Proteica , Ratos , Proteínas Recombinantes de Fusão/químicaRESUMO
Functional tissue engineering strategies provide innovative approach for the repair and regeneration of damaged cartilage. Hydrogel is widely used because it could provide rapid defect filling and proper structure support, and is biocompatible for cell aggregation and matrix deposition. Efforts have been made to seek suitable scaffolds for cartilage tissue engineering. Here Alg-DA/Ac-ß-CD/gelatin hydrogel was designed with the features of physical and chemical multiple crosslinking and self-healing properties. Gelation time, swelling ratio, biodegradability and biocompatibility of the hydrogels were systematically characterized, and the injectable self-healing adhesive hydrogel were demonstrated to exhibit ideal properties for cartilage repair. Furthermore, the new hydrogel design introduces a pre-gel state before photo-crosslinking, where increased viscosity and decreased fluidity allow the gel to remain in a semi-solid condition. This granted multiple administration routes to the hydrogels, which brings hydrogels the ability to adapt to complex clinical situations. Pulsed electromagnetic fields (PEMF) have been recognized as a promising solution to various health problems owing to their noninvasive properties and therapeutic potentials. PEMF treatment offers a better clinical outcome with fewer, if any, side effects, and wildly used in musculoskeletal tissue repair. Thereby we propose PEMF as an effective biophysical stimulation to be 4th key element in cartilage tissue engineering. In this study, the as-prepared Alg-DA/Ac-ß-CD/gelatin hydrogels were utilized in the rat osteochondral defect model, and the potential application of PEMF in cartilage tissue engineering were investigated. PEMF treatment were proven to enhance the quality of engineered chondrogenic constructs in vitro, and facilitate chondrogenesis and cartilage repair in vivo. All of the results suggested that with the injectable self-healing adhesive hydrogel and PEMF treatment, this newly proposed tissue engineering strategy revealed superior clinical potential for cartilage defect treatment.
RESUMO
Lacking self-repair abilities, injuries to articular cartilage can lead to cartilage degeneration and ultimately result in osteoarthritis. Tissue engineering based on functional bioactive scaffolds are emerging as promising approaches for articular cartilage regeneration and repair. Although the use of cell-laden scaffolds prior to implantation can regenerate and repair cartilage lesions to some extent, these approaches are still restricted by limited cell sources, excessive costs, risks of disease transmission and complex manufacturing practices. Acellular approaches through the recruitment of endogenous cells offer great promise for in situ articular cartilage regeneration. In this study, we propose an endogenous stem cell recruitment strategy for cartilage repair. Based on an injectable, adhesive and self-healable o-alg-THAM/gel hydrogel system as scaffolds and a biophysio-enhanced bioactive microspheres engineered based on hBMSCs secretion during chondrogenic differentiation as bioactive supplement, the as proposed functional material effectively and specifically recruit endogenous stem cells for cartilage repair, providing new insights into in situ articular cartilage regeneration.
RESUMO
Urinary tract infection (UTI) caused by uropathogens is the most common infectious disease and significantly affects all aspects of the quality of life of the patients. However, uropathogens are increasingly becoming antibiotic-resistant, which threatens the only effective treatment option available-antibiotic, resulting in higher medical costs, prolonged hospital stays, and increased mortality. Currently, people are turning their attention to the immune responses, hoping to find effective immunotherapeutic interventions which can be alternatives to the overuse of antibiotic drugs. Bladder infections are caused by the main nine uropathogens and the bladder executes different immune responses depending on the type of uropathogens. It is essential to understand the immune responses to diverse uropathogens in bladder infection for guiding the design and development of immunotherapeutic interventions. This review firstly sorts out and comparatively analyzes the immune responses to the main nine uropathogens in bladder infection, and summarizes their similarities and differences. Based on these immune responses, we innovatively propose that different microbial bladder infections should adopt corresponding immunomodulatory interventions, and the same immunomodulatory intervention can also be applied to diverse microbial infections if they share the same effective therapeutic targets.
Assuntos
Cistite , Infecções Urinárias , Antibacterianos/uso terapêutico , Humanos , Imunidade , Qualidade de Vida , Bexiga Urinária , Infecções Urinárias/etiologia , Infecções Urinárias/terapiaRESUMO
Chronic skin wounds impose immense suffers and economic burdens. Current research mainly focuses on acute wound management which exhibits less effective in chronic wound healing. Growth differentiation factor 11 (GDF11) has profound effects on several important physiological processes related to chronic wound healing, such as inflammation, cell proliferation, migration, angiogenesis, and neurogenesis. This review summarizes recent advances in biology of chronic wounds and the potential role of GDF11 on wound healing with its regenerative effects, as well as the potential delivery methods of GDF11. The challenges and future perspectives of GDF11-based therapy for chronic wound care are also discussed. The Translational Potential of this Article: This review summarized the significance of GDF11 in the modulation of inflammation, vascularization, cell proliferation, and remodeling, which are important physiological processes of chronic wound healing. The potential delivery methods of GDF11 in the management of chronic wound healing is also summarized. This review may provide potential therapeutic approaches based on GDF11 for chronic wound healing.
RESUMO
We develop a poly (lactic-co-glycolic acid)/ß-calcium phosphate (PLGA/TCP)-based scaffold through a three-dimensional (3D) printing technique incorporating icaritin (ICT), a unique phytomolecule, and secretome derived from human fetal mesenchymal stem cells (HFS), to provide mechanical support and biological cues for stimulating bone defect healing. With the sustained release of ICT and HFS from the composite scaffold, the cell-free scaffold efficiently facilitates the migration of MSCs and promotes bone regeneration at the femoral defect site in the ovariectomy (OVX)-induced osteoporotic rat model. Furthermore, mechanism study results indicate that the combination of ICT and HFS additively activates the Integrin-FAK (focal adhesion kinase)-ERK1/2 (extracellular signal-regulated kinase 1/2)-Runx2 (Runt-related transcription factor 2) axis, which could be linked to the beneficial recruitment of MSCs to the implant and subsequent osteogenesis enhancement. Collectively, the PLGA/TCP/ICT/HFS (P/T/I/S) bioactive scaffold is a promising biomaterial for repairing osteoporotic bone defects, which may have immense implications for their translation to clinical practice.
RESUMO
BACKGROUND: There has been a surge of interest on velocity-based training (VBT) in recent years. However, it remains unclear whether VBT is more effective in improving strength, jump, linear sprint and change of direction speed (CODs) than the traditional 1RM percentage-based training (PBT). OBJECTIVES: To compare the training effects in VBT vs. PBT upon strength, jump, linear sprint and CODs performance. DATA SOURCES: Web of science, PubMed and China National Knowledge Infrastructure (CNKI). STUDY ELIGIBILITY CRITERIA: The qualified studies for inclusion in the meta-analysis must have included a resistance training intervention that compared the effects of VBT and PBT on at least one measure of strength, jump, linear sprint and CODs with participants aged ≥16 yrs. and be written in English or Chinese. METHODS: The modified Pedro Scale was used to assess the risk of bias. Random-effects model was used to calculate the effects via the mean change and pre-SD (standard deviation). Mean difference (MD) or Standardized mean difference (SMD) was presented correspondently with 95% confidence interval (CI). RESULTS: Six studies met the inclusion criteria including a total of 124 participants aged 16 to 30 yrs. The differences of training effects between VBT and PBT were not significant in back squat 1RM (MD = 3.03kg; 95%CI: -3.55, 9.61; I2 = 0%) and load velocity 60%1RM (MD = 0.02m/s; 95%CI: -0.01,0.06; I2 = 0%), jump (SMD = 0.27; 95%CI: -0.15,0.7; I2 = 0%), linear sprint (MD = 0.01s; 95%CI: -0.06, 0.07; I2 = 0%), and CODs (SMD = 0.49; 95%CI: -0.14, 1.07; I2 = 0%). CONCLUSION: Both VBT and PBT can enhance strength, jump, linear sprint and CODs performance effectively without significant group difference.
Assuntos
Treinamento Resistido , China , Coleta de Dados , Feminino , Humanos , MasculinoRESUMO
Overactive bladder (OAB) is a common condition that affects a significant patient population. The N-methyl-D-aspartate receptor (NMDAR) has a role in developing bladder overactivity, pharmacological inhibition of which inhibits bladder overactivity. The common pathogenesis of OAB involves bladder smooth muscle (BSM) overactivity. In this study, a smooth muscle-specific NMDAR knockout (SMNRKO) mouse model was generated. The bladders from SMNRKO mice displayed normal size and weight with an intact bladder wall and well-arranged BSM bundles. Besides, SMNRKO mice had normal voiding patterns and urodynamics and BSM contractility, indicating that NMDAR in BSM was not essential for normal physiological bladder morphology and function. Unexpectedly, cyclophosphamide (CYP)-treated SMNRKO and wild-type (WT) mice had similar pathological changes in the bladder. Furthermore, SMNRKO mice displayed similar altered voiding patterns and urodynamic abnormalities and impaired BSM contractility compared with WT mice after CYP treatment. MK801 partially reversed the pathological bladder morphology and improved bladder dysfunction induced by CYP, but did not cause apparent differences between WT mice and SMNRKO mice, suggesting that NMDAR in BSM was not involved in pathological bladder morphology and function. Moreover, the direct instillation of NMDAR agonists or antagonists into the CYP-induced OAB did not affect bladder urodynamic function, indicating that NMDAR in BSM was not the pharmacotherapy target of MK801 for CYP-induced cystitis. The findings indicated that NMDAR in BSM was not essential for normal physiological or pathological bladder morphology and function, and MK801 improving pathological bladder function was not mediated by an action on NMDAR in BSM.
RESUMO
The development of an excellent, bioabsorbable hemostatic material for deep wound remains a challenge. In this work, a biodegradable cotton-like biomimetic fibrous mat of poly (l-lactic acid) (PLLA) was made by melt spinning. Subsequently, SD composite was prepared by cross-linking sodium alginate (SA) with dopamine (DA). It was immobilized on the fibre surface, which inspired by mussel byssus. Finally, Fe3+ was loaded onto the 0.5SD/PLLA composite by chelation with the carboxyl of alginate and phenolic hydroxy of dopamine. The haemostasis experiment found that the hemostatic time 47 s in vitro. However, the bleeding volume was 0.097 g and hemostatic time was 23 s when 20Fe3+-0.5SD/PLLA was applied in the haemostasis of the rat liver. As a result of its robust hydrophilicity and bouffant cotton-like structure, it could absorb a large water from blood, which could concentrate the component of blood and reduce the clotting time. Furthermore, the addition of Fe3+ in the 0.5SD/PLLA had a significant effect on improve hemostatic property. It also displayed excellent antibacterial property for Escherichia coli and Staphylococcus aureus. Notably, it possesses superior hemocompatibility, cytocompatibility and histocompatibility. Hence, 20Fe3+-0.5SD/PLLA has high potential application in haemostasis for clinical settings due to its outstanding properties.
RESUMO
An effective treatment for spinal cord injury (SCI) remains a severe clinical challenge due to the intrinsically limited regenerative capacity and complex anatomical structure of the spinal cord. The combination of biomaterials, which serve as scaffolds for axonal growth, cells and neurotrophic factors, is an excellent candidate for spinal cord regeneration. Herein, a new micropatterned conductive electrospun nanofiber mesh was constructed with poly{[aniline tetramer methacrylamide]-co-[dopamine methacrylamide]-co-[poly(ethylene glycol) methyl ether methacrylate]}/PCL (PCAT) using a rotation electrospinning technology. The aim was to study the synergistic effects of electrical stimulation (ES) and a micropatterned conductive electrospun nanofiber mesh incorporated with nerve growth factor (NGF) on the differentiation of rat nerve stem cells (NSCs). The hydrophilicity of the conductive nanofiber mesh could be tailored by changing the dopamine (DA) and aniline tetramer (AT) content from 19° to 79°. A favorable electroactivity and conductivity was achieved by the AT segment of PCAT. The as-fabricated micropatterned electrospun nanofiber mesh possessed a regularly aligned valley and ridge structure, and the diameter of the nanofiber was 312 ± 58 nm, while the width of the valley and ridge was measured to be 210 ± 17 µm and 200 ± 16 µm, respectively. The growth and neurite outgrowth of differentiated NSCs were observed along the valley of the micropatterned nanofiber mesh. In addition, the NGF loaded micropatterned conductive electrospun nanofiber mesh combined with ES exhibited the highest cell viability, and effectively facilitated the differentiation of NSCs into neurons and suppressed the formation of astrocytes, thus exhibiting a great application potential for nerve tissue engineering.
Assuntos
Nanofibras/química , Regeneração Nervosa , Células-Tronco Neurais/citologia , Engenharia Tecidual , Alicerces Teciduais/química , Animais , Adesão Celular , Diferenciação Celular , Células Cultivadas , Condutividade Elétrica , Estimulação Elétrica , Camundongos , Estrutura Molecular , Células NIH 3T3 , Fator de Crescimento Neural/química , Células PC12 , Tamanho da Partícula , Polímeros/química , Ratos , Propriedades de SuperfícieRESUMO
Three-dimensional (3D) fibrous scaffolds allowing sufficient cell infiltration are urgently needed for bone tissue engineering. In this study, a highly permeable 3D interconnected scaffold was fabricated by surface bonding of cotton-like nonwoven fibers with micro- and nanoscale architecture using gaseous chloroform. The results of physiochemical characterization indicated that bonding for 90 min with a fiber density of 0.15 g/cm3 could facilitate satisfactory porosity, supportive mechanical properties, and a 3D spatial microstructure for cell ingrowth. Coating with gelatin on the fibers induced highly efficient in vitro mineralization and in vivo bone formation as indicated by mineral deposition and repair of rabbit radius bone defect. The findings from this work demonstrated that these biofunctionalized fibrous scaffolds could bionically represent topographic nanofeatures and biological composition for cell binding affinities similar to those of the natural extracellular matrix (ECM). It can be concluded that the facile fabrication and modification strategy of 3D fibrous scaffolds exhibit promising prospect to fulfill the progressive needs in bone tissue engineering.
RESUMO
Electrically conducting polymers have been emerging as intelligent bioactive materials for regulating cell behaviors and bone tissue regeneration. Additionally, poor adhesion between conventional implants and native bone tissue may lead to displacement, local inflammation, and unnecessary secondary surgery. Thus, a conductive bioadhesive with strong adhesion performance provides an effective approach to fulfill fixation and regeneration of comminuted bone fracture. Inspired by mussel chemistry, we designed the conductive copolymers poly{[aniline tetramer methacrylamide]-co-[dopamine methacrylamide]-co-[poly(ethylene glycol) methyl ether methacrylate]} [poly(ATMA-co-DOPAMA-co-PEGMA); AT:conductive aniline tetramer; DOPA:dopamine; PEG:poly(ethylene glycol))] with AT content 3.0, 6.0, and 9.0 mol %, respectively. The adhesive strength of this copolymer was enhanced during tensile process perhaps due to the synergistic effects of H-bonding, π-π interactions, and polymer long-chain entanglement, reaching up to 1.28 MPa with 6 mol % AT. Biological characterizations of preosteoblasts indicated that the bioadhesives exhibited desirable biocompatibility. In addition, the osteogenic differentiation was synergistically enhanced by the conductive substrate and electrical stimulation with a square wave, frequency of 100 Hz, 50% duty cycle, and electrical potential of 500 mV, as indicated by ALP activity, calcium deposition, and expression of osteogenic genes. The ALP activity at 14 days and calcium deposition at 28 days on the 9 mol % AT group were significantly higher than that on PLGA under electrical stimulation. The expression value of OPN for 9 mol % AT group was notably upregulated by 5.9-fold compared with PLGA at 7 days under electrical stimulation. Overall, the conductive polymers with strong adhesion can synergistically upregulate the cellular activity combining with electrical stimulation and might be a promising bioadhesive for orthopedic and dental applications.
Assuntos
Adesivos , Engenharia Tecidual , Compostos de Anilina , Osso e Ossos , Osteogênese , PolímerosRESUMO
Functional biomaterials with magnetic properties are considerably useful for regulating cell behavior and promoting bone regeneration. And the combination of such biomaterials with physical environmental cues (such as magnetic fields and mechanical stress) might be more favorable for the regulation of cell function. This study is aimed at investigating the combined effects of magnetically responsive materials and a static magnetic field (SMF) on the osteogenic differentiation of osteoblasts and the potential mechanism involved. In this study, oleic acid modified iron oxide nanoparticles (IO-OA NPs) were utilized to generate homogeneous magnetic nanocomposites with poly(lactide-co-glycolide) (PLGA) used as the base and to enhance the mechanical properties of the composites. In vitro experimental results show that in the presence of an external SMF, cell attachment and osteogenic differentiation were significantly improved using the IO-OA/PLGA composites, as indicated by enhanced alkaline phosphatase (ALP) activity, increased mineralized nodule formation, and upregulated bone-associated gene expression (ALP, OCN, and BMP2), in a dose- and time-dependent manner. Furthermore, the upregulated expression levels of piezo-type mechanosensitive ion channel component 1 (Piezo1), a key receptor for sensing mechanical stimuli, implied that the synergistically enhanced osteogenic differentiation was mainly caused as a result of the mechanical stimuli. Such magnetically actuated mechanical stimuli were induced through the nano-deformation of the magnetic substrate under a SMF, which was directly characterized via in situ scanning using atomic force microscopy (AFM). This study demonstrates that magnetically actuated nano-mechanical stimuli may underpin the synergistic effects of magnetic composites and magnetic stimuli to enhance osteogenic differentiation, and they could form the basis of a potential strategy to accelerate bone formation for bone tissue engineering and regenerative medicine applications.
Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Campos Magnéticos , Osteogênese , Animais , Regeneração Óssea , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Nanopartículas de Magnetita/química , Camundongos , Nanocompostos/química , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Engenharia TecidualRESUMO
Three-dimensional (3D) composite porous scaffolds containing hydroxyapatite (HA) and polymer matrix showed wide applications in bone repair because of their improved biocompatibility, bioactivity, and mechanical properties in our previous studies. In this work, mesoporous hydroxyapatite (MHA) surface-modified by poly(γ-benzyl-l-glutamate) (PBLG) with different amounts (from 11 to 50 wt %) was synthesized by the in situ ring opening polymerization of γ-benzyl-l-glutamate N-carboxy anhydride (BLG-NCA) and then PBLG-g-MHA/PLGA composite films were prepared to illustrate the biological performance of the composites. Furthermore, porous scaffolds of PBLG-g-MHA/PLGA were fabricated through modified solvent casting/particulate leaching (SC/PL) method to demonstrate the ability of in vivo bone defect repair. In vitro cytological assay indicated that enhanced cell expansion on PBLG-g-MHA/PLGA with 11 wt % PBLG amounts and improved osteogenic differentiation on the composites with 33 and 50 wt % PBLG amounts were achieved. And the porous scaffolds exhibited high porosity and interconnected pores. Results of the in vivo rabbit radius defect repair indicated that rapid mineralization and new bone formation could be observed on the composites with 22 and 33 wt % PBLG. This study revealed that PBLG-g-MHA/PLGA composites might have potential applications in clinical bone repair.
RESUMO
Differently sized poly(lactic-co-glycolic) microspheres were efficiently prepared with electrified liquid jets and a phase separation technique for a wide range of applications. Higher polymer concentrations tended to form larger microcarriers. Polymer concentration can obviously affect bead or fiber formation resulting beads and fiber morphologies. As the voltage of electrostatic field and the needle size increased, the size of microcarriers decreased remarkably. The most suitable concentration of ethanol in the collecting solution might be lower than 55%. The resulting composite microcarriers have significantly narrow size distribution, controllable sizes, and high cell adhesion, growth, and osteodifferentiation abilities.
RESUMO
The highly damaging state of spinal cord injuries has provided much inspiration for the design of surface modification of the implants that can promote nerve regeneration and functional reconstruction. DOPA-IGF-1, a new recombinant protein designed in our previous study, exhibited strong binding affinity to titanium and significantly enhanced the growth of NIH3T3 cells on the surface of titanium with the same biological activity as IGF-1. In this article, surface modification of poly(lactide-co-glycolide) (PLGA) films with recombinant DOPA-IGF-1 was performed to promote the paracrine activity of human umbilical cord mesenchymal stem cells (hUCMSCs) by secreting neurotrophic factors. DOPA-IGF-1 exhibited the strongest binding ability to PLGA films than commercial IGF-1 and nonhydroxylated YKYKY-IGF-1. In vitro cultures of hUCMSCs on the modified PLGA films showed that DOPA-IGF-1@PLGA substrates significantly improved the proliferation, adhesion, and neurotrophic factors secretion of hUCMSCs, especially for nerve growth factor, as confirmed by qRT-PCR and western blot analysis. Subsequently, the acquired neurotrophic factors secreted by the hUCMSCs cultured on the DOPA-IGF-1@PLGA films obviously enhanced neurite outgrowth of PC12 cells. Taken together, PLGA substrates with DOPA-IGF-1 immobilization is a promising platform for neural tissue engineering via neurotrophic factors secretion from MSCs and should be further tested in vivo.
Assuntos
Adesivos/química , Di-Hidroxifenilalanina/química , Fator de Crescimento Insulin-Like I/química , Fator de Crescimento Insulin-Like I/farmacologia , Neuritos/efeitos dos fármacos , Polímeros/química , Animais , Linhagem Celular , Linhagem Celular Tumoral , Células Cultivadas , Humanos , Camundongos , Células NIH 3T3 , Células PC12 , Ratos , Engenharia Tecidual/métodosRESUMO
Large-scale cell culture for cell expansion in tissue engineering is currently a major focus of research. One method to achieve better cell amplification is to utilize microcarriers. In this study, different amounts of poly(γ-benzyl-l-glutamate) (PBLG) (from 11 wt% to 50 wt%) were grafted on mesoporous hydroxyapatite (MHA) by the in situ ring opening polymerization of γ-benzyl-l-glutamate N-carboxyanhydride (BLG-NCA), and biodegradable and biocompatible PBLG-g-MHA microcarriers were directly fabricated using the oil-in-water (O/W) solvent-evaporation technique for bone tissue engineering. The amount of grafted PBLG could be controlled by adjusting the feed ratio of MHA and BLG-NCA. The relationships between sphere morphology and graft amount or solution concentration were explored. Furthermore, cytological assays were performed to evaluate the biological properties of the PBLG-g-MHA microcarriers. For a solution concentration of 3% (w/v) and PBLG graft amounts of 33 wt% and 50 wt%, the microspheres could be harvested with optimal spherical shapes. In vitro cell culture revealed that the PBLG-g-MHA microspheres had favorable properties for cell proliferation and significantly enhanced the osteogenic differentiation of MC3T3-E1 cells and bone matrix formation.