Clinical Study on Electronic Medical Neuroelectric Stimulation Based on the Internet of Things to Treat Epilepsy Patients with Anxiety and Depression.

With the continuous development and improvement of the level of medical technology in our country in recent years, the treatment of epilepsy has been constantly updated and developed. Nerve electrical stimulation is considered to be a very effective method for treating epilepsy with anxiety and depression. There are many traditional methods for the treatment of epilepsy. For example, vagus nerve stimulation (VNS) has been applied earlier, and the therapeutic effect has been confirmed, but it will cause serious complications and is easier to be uncomfortable; deep brain stimulation for epilepsy is still in the immature stage, and there is no final conclusion. Therefore, this article proposes a clinical study on the treatment of patients with epilepsy with anxiety and depression based on the electronic medical nerve stimulation of the Internet of Things. First of all, this article uses the literature method to study the causes of epilepsy and previous treatment methods. Then, we designed an experimental study of epilepsy with depression based on the Internet of Things electronic medical neuroelectric stimulation therapy and selected the core quality of life questionnaire, SDS, and SAS as observation indicators. Finally, the comparison of epilepsy symptoms and depression and anxiety between the control group and the observation group before and after treatment was analyzed. The results of the experiment showed that, among the 50 subjects in the study, the observation group that used electrical nerve stimulation therapy had 5 people who stopped seizures after treatment, accounting for 10%, while in the control group of traditional drug treatment methods, after treatment, only one person stopped the seizure, accounting for 2%. In addition, the SAS and SDS scores of the observation group were also lower than those of the control group. Therefore, the use of nerve electrical stimulation to treat epilepsy with anxiety and depression symptoms has better performance and can help patients recover as soon as possible.

An abluminal biodegradable polymer sirolimus-eluting stent versus a durable polymer everolimus-eluting stent in patients undergoing coronary revascularization: 3-year clinical outcomes of a randomized non-inferiority trial.

The Cordimax stent has proved non-inferior to the Cypher Select durable polymer sirolimus-eluting stent for the primary endpoint of angiographic in-stent late luminal loss and in-stent mean diameter stenosis at 9 months. The trial was designed to compare the efficacy and safety of the Cordimax stent with the Xience V stent in patients undergoing coronary revascularization. This randomized, multicenter trial enrolled 3697 patients treated with Cordimax stent (2460 patients) and Xience V stent (1237 patients). The primary efficacy endpoint was a target-lesion failure (TLF) at 1 year and the primary safety endpoint was a composite of death or myocardial infarction (MI) at 3 years. 3399 patients (91.9%) completed 3-year follow-up. At 1 year, the primary efficacy endpoint occurred in 86 (3.5%) patients in the Cordimax group versus 40 (3.2%) patients in the Xience V group (0.3% absolute risk difference, 95% CI -1.0-1.5%, Pnon-inferiority < 0.0001). At 3 years, the primary safety endpoint occurred in 39 (1.6%) patients in the Cordimax group versus 19 (1.5%) patients in the Xience V group (0.05% absolute risk difference, 95% CI -0.8-0.9%, Pnon-inferiority < 0.0001). The incidence of target lesion revascularization was low in Cordimax group compared with Xience V group (3.6% versus 5.1%, P = 0.03). There were no differences between Cordimax and Xience V in terms of Cardiac death (0.3% versus 0.4%, P = 0.70), myocardial infarction (1.2% versus 0.9%, P = 0.37), and the stent thrombosis (0.4% versus 0.6%, P = 0.61). In conclusion, safety and efficacy outcomes of Cordimax stent were non-inferior to the Xience V stent 3 years after stent implantation.

Surface Modification of Aliphatic Polyester to Enhance Biocompatibility.

Aliphatic polyester is a kind of biodegradable implantable polymers, which shows promise as scaffolds in tissue engineering, drug carrier, medical device, and so on. To further improve its biocompatibility and cell affinity, many techniques have been used to modify the surface of the polyester. In the present paper, the key factors of influencing biocompatibility of aliphatic polyester were illuminated, and the different surface modification methods such as physical, chemical, and plasma processing methods were also demonstrated. The advantages and disadvantages of each method were also discussed with the hope that this review can serve as a resource for selection of surface modification of aliphatic products.

Drug release kinetics from a drug-eluting stent with asymmetrical coat.

The aim of this study was to investigate the drug release profiles of biodegradable polymer sirolimus- or paclitaxel-eluting stents with asymmetrical coating (BPSES-A or BPPES-A) both in vitro and in vivo. In vitro, the drug release profile was characterized by measuring the drug concentration by HPLC over a time-course. In vivo, a porcine aorta stenting model was employed. The results showed that the drug release rates of BPSES-A and BPPES-A were slower, more stable and less burst releasing than those of conventionally coated stents (BPSES-C and BPPES-C respectively), both in vitro and in vivo. Based on the in vivo results, the sirolimus and paclitaxel content of the local coronary wall was maintained at a higher and more effective level with BPSES-A and BPPES-A than with BPSES-C and BPPES-C, respectively. The drug levels in peripheral tissue samples were below detection levels. These data demonstrated the effectiveness of both sirolimus and paclitaxel as stent coating agents, and revealed the favorable drug release kinetics and pharmacokinetics of asymmetrical coated stents compared with conventional coated stents.

Randomized clinical trial comparing abluminal biodegradable polymer sirolimus-eluting stents with durable polymer sirolimus-eluting stents: Nine months angiographic and 5-year clinical outcomes.

BACKGROUND: The biodegradable polymer drug-eluting stents (DES) were developed to improve vascular healing. However, further data and longer-term follow-up are needed to confirm safety and efficacy of these stents. This randomized clinical trial aimed to compare safety and efficacy of 2 sirolimus-eluting stents (SES): Cordimax-a novel abluminal biodegradable polymer SES and Cypher Select-a durable polymer SES, at 9 months angiographic and 5-year clinical follow-up. METHODS: We randomized 402 patients with coronary artery disease to percutaneous coronary intervention with Cordimax (n = 202) or Cypher select (n = 200). Angiographic follow-up was performed at 9 months after the index procedure and clinical follow-up annually up to 5 years. The primary endpoint was angiographic in-stent late luminal loss (LLL). Secondary endpoints included angiographic restenosis rate, target vessel revascularization (TVR), and major adverse cardiac events (MACEs; defined as cardiac death, myocardial infarction, or TVR) at 5-year follow-up. RESULTS: Cordimax was noninferior to Cypher select for in-stent LLL (0.25 ±â€Š0.47 vs 0.18 ±â€Š0.49 mm; P = 0.587) and in-stent mean diameter stenosis (22.19 ±â€Š12.21% vs 19.89 ±â€Š10.79%; P = 0.064) at 9 months angiographic follow-up. The MACE rates were not different at 1 year (5.9% vs 4.0%, P = 0.376); however, MACE rates from 2 to 5 years were lower in the Cordimax group (6.8% vs 13.1%; P = 0.039). CONCLUSION: Abluminal biodegradable polymer SES is noninferior to durable polymer SES at 9-month angiographic and 1-year clinical follow-up. However, MACE rates from 2 to 5 years were less in the abluminal biodegradable polymer group.

No Effect of Rapamycin on Cardiac Adhesion Formation: A Drug-Loaded Bioresorbable Polylactone Patch in a Porcine Cardiac Surgical Model.

BACKGROUND: The fusing of the epicardium and sternum due to adhesion is a common problem during repeated cardiac surgery and carries with it an increased risk of bleeding. The use of barriers and patches has been tested to prevent the formation of adhesions, but the very presence of a patch can provoke adhesion formation. The objective of this study was, therefore, to investigate both biodegradable and bioresorbable polylactone patches [(polycaprolactone-poly(ethylene oxide)-polycaprolactone tri-block copolymer (PCE)]. The patches were also tested with a controlled release of rapamycin, which prevents cell migration and extracellular matrix deposition. The clinical effectiveness of rapamycin in pericardial patches has not previously been examined. MATERIALS AND METHODS: Three groups of 6 female Danish Landrace pigs underwent sternotomy and abrasion of the epicardium, before being randomized to either group 1--the control group (with no patch), group 2--PCE patch implanted between the sternum and epicardium, or group 3--PCE patch and slow-release 1.6-mg rapamycin. After a median time period of 26 days, the pigs were euthanized and their hearts removed en bloc with the sternum, for macroscopic, histological and pathological examination. RESULTS: Upon macroscopic examination, a significantly lower degree of adhesion in group 2, as compared to group 1 (p < 0.05), was found. Histological analysis of the tissues showed significantly more fibrosis, inflammation and foreign body granulomas (p < 0.05) in both group 2 and group 3, when compared to group 1. CONCLUSION: A PCE patch following sternotomy in animal subjects reduces postoperative macroscopic adhesions without reducing microscopic fibrosis or inflammation. Loading the patch with rapamycin was found not to increase the antifibrotic effect.

Solely abluminal drug release from coronary stents could possibly improve reendothelialization.

OBJECTIVES: To compare a new stent with an asymmetric coating, eluting the drug to the abluminal surface, to a stent with a conventional coating eluting the drug both to the luminal and the abluminal side. BACKGROUND: Stents with asymmetric coating, eluting the drug to the vessel wall (BPSES-A), could potentially give faster reendothelialization after percutaneous coronary interventions (PCI) and decrease in in-stent thrombosis and late restenosis. METHODS: BPSES-A, conventional coated stents (BPSES-C), biodegradable polymer stents without drug (BPS, for control), and bare metal stents (BMS, for control) were implanted into the coronary arteries of 38 pigs (75 stents). Pigs were sacrificed after 4, 12, and 24 weeks. Quantitative coronary angiography was used to compare in-stent late lumen loss (LLL) and electron microscopy was used to reveal levels of reendothelialization. RESULTS: The stents were all successfully implanted. LLL of BPSES-A, BPSES-C, BMS, and BPS were 0.56 ± 0.51, 0.60 ± 0.58, 0.89 ± 0.43, and 1.68 ± 0.30 mm, respectively, after 4 weeks. LLL of BPSES-A and BPSES-C were 0.63 ± 0.53 and 0.69 ± 0.24 mm, respectively, after 12 weeks. LLL of BPSES-A, BPSES-C, and BMS were 0.42 ± 0.15 m, 0.56 ± 0.28 mm, and 0.99 ± 0.13 mm, respectively, after 24 weeks. The scaling of reendothelialization was as follows: after 4 weeks BMS > = BPS > BPSES-A > BPSES-C, after 12 weeks BPSES-A > BPSES-C, and after 24 weeks BMS > BPSES-A > BPSES-C. Reendothelialization was better in BPSES-A than BPSES-C (P < 0.05). There was no correlation between LLL and reendothelialization (P = 0.42). CONCLUSION: Asymmetric coating of coronary stents might be helpful to improve reendothelialization. © 2016 Wiley Periodicals, Inc.

Self-assembly of dual drug-delivery coating for synergistic bone regeneration.

Bone regeneration for the treatment of bone diseases represents a major clinical need. Introducing recombinant human bone morphogenetic protein-2 (rhBMP-2) into biomaterials is an extensively used approach to induce osteogenic differentiation and accelerate bone regeneration. However, serious adverse events can occur in the event of an overdose of rhBMP-2. Dexamethasone (DEX) is a synthetic hydrophobic glucocorticoid, which can enhance rhBMP-2-induced osteogenic differentiation by binding to a glucocorticoid receptor intracellularly. In this study, we have developed a multilayered composite coating made of poly(l-lactide-co-glycolide) (PLGA) nanoparticles, heparin and chitosan to deliver DEX and rhBMP-2 dually. The coating can reserve DEX and rhBMP-2 using the building blocks of the PLGA nanoparticles and heparin. Sustained release of DEX and rhBMP-2 by this coating was achieved. Moreover, a flow cytometry assay suggests that the PLGA nanoparticles could be transported across the cell membrane and presumably could improve the intracellular delivery of DEX via cell internalization. The in vitro osteogenesis studies reveal that the dual drug-loaded coating has a synergistic osteogenic differentiation effect on C2C12 myoblasts, as indicated by the upregulation of the alkaline phosphatise activity and osteo-related gene expression. In addition, µCT and histological analysis of the in vivo experiments demonstrate that the dual drug-loaded coating induced more ectopic bone formation than the individual drug-loaded coating. Therefore, this study demonstrates that our coating system can reserve these two drugs and deliver them locally to cells with the ability to induce rapid osteogenic differentiation and bone regeneration synergistically. Compared to other reported DEX/rhBMP-2 delivery systems, our coating system represents a simple, safe and effective dual drug delivery alternative. Moreover, since a layer-by-layer strategy is easily applied onto varying substrates, our coating system can be combined with many commercially available or existing biomaterials to improve their osteogenetic performance.

Fabrication and effect on regulating vSMC phenotype of a biomimetic tunica media scaffold.

An ideal vascular tissue engineering scaffold should imitate physical and biochemical cues in native vessels for guiding cell growth, differentiation and tissue formation. The tunica media provides a key structure and function support for native vessels. In this study, a film-like MNP-TGF/bFGF-PLGA scaffold that simulated physical and biochemical cues of tunica media in native vessels was fabricated by soft lithography combined with solution casting and phase separation technique. The scaffold had dual surface topographies of parallel arranged microgrooves and nanofiber structures, and interconnected pores to be able to deliver nutrient and eliminate metabolized products. The TGF-ß1 and bFGF immobilized on the scaffold by silica nanoparticle binding and plasma treatment technique could maintain continuous release for 10 and 7 days, respectively. The synergy effect of the dual surface topography and released growth factors endowed the MNP-TGF/bFGF-PLGA scaffold with good capacity on regulating vascular smooth muscle cell (vSMC) phenotype. Importantly, the scaffold possessed good mechanical properties and could easily be rolled into a multilayer cylindrical tube as a promising biomimic vascular tissue engineering scaffold.

Mesenchymal stem cells attenuated PLGA-induced inflammatory responses by inhibiting host DC maturation and function.

The poly lactic-co-glycolic acid (PLGA) bio-scaffold is a biodegradable scaffold commonly used for tissue repair. However, implanted PLGA scaffolds usually cause serious inflammatory responses around grafts. To improve PLGA scaffold-based tissue repair, it is important to control the PLGA-mediated inflammatory responses. Recent evidence indicated that PLGA induce dendritic cell (DC) maturation in vitro, which may initiate host immune responses. In the present study, we explored the modulatory effects of mesenchymal stem cells (MSC) on PLGA-induced DCs (PLGA-DC). We found that mouse MSCs inhibited PLGA-DC dendrite formation, as well as co-stimulatory molecule and pro-inflammatory factor expression. Functionally, MSC-educated PLGA-DCs promoted Th2 and regulatory T cell differentiation but suppressed Th1 and Th17 cell differentiation. Mechanistically, we determined that PLGA elicited DC maturation via inducing phosphorylation of p38/MAPK and ERK/MAPK pathway proteins in DCs. Moreover, MSCs suppressed PLGA-DCs by partially inactivating those pathways. Most importantly, we found that the MSCs were capable of suppressing DC maturation and immune function in vivo. Also, the proportion of mature DCs in the mice that received MSC-PLGA constructs greatly decreased compared with that of their PLGA-film implantation counterparts. Additionally, MSCs co-delivery increased regulatory T and Th2 cells but decreased the Th1 and Th17 cell numbers in the host spleens. Histological analysis showed that MSCs alleviated the inflammatory responses around the grafted PLGA scaffolds. In summary, our findings reveal a novel function for MSCs in suppressing PLGA-induced host inflammatory response and suggest that DCs are a new cellular target in improving PLGA scaffold-based tissue repair.

Isoniazid conjugated poly(lactide-co-glycolide): long-term controlled drug release and tissue regeneration for bone tuberculosis therapy.

Bone tuberculosis (TB) is one of the most common extrapulmonary TB. Effective integration of chemotherapy and bone regeneration is an optimal solution for bone TB therapy. Herein, we produce a composite scaffold drug delivery system fabricated with an isoniazid conjugated star poly(lactide-co-glycolide) (PLGA-INH4) and ß-TCP. The cytological assay indicated the composite system possesses good biocompatibility. The in vitro and in vivo drug release evaluations showed that the composite system can intactly release the pristine INH and maintain effective INH concentration in a controlled manner for more than 100 days, and achieve high localized drug concentration and low systemic drug concentration. The rabbit radius repair experiment testified the scaffold has good bone regeneration capacity. Our work demonstrate the composite system can simultaneously achieve localized long-term drug controlled release and bone regeneration, which provides a promising route for improved bone TB treatment.

In vitro and in vivo drug release behavior and osteogenic potential of a composite scaffold based on poly(ε-caprolactone)-block-poly(lactic-co-glycolic acid) and ß-tricalcium phosphate.

To cure serious bone tuberculosis, a novel long-term drug delivery system was designed and prepared to satisfy the needs of both bone regeneration and antituberculous drug therapy. An antituberculous drug (rifampicin, RFP) was loaded into a porous scaffold, which composed of a newly designed polylactone, poly(ε-caprolactone)-block-poly(lactic-co-glycolic acid) (b-PLGC) copolymer, and ß-tricalcium phosphate (ß-TCP). The releasing results demonstrated that RFP could be steadily released for as long as 12 weeks both in vitro and in vivo. During the in vivo experimental period, the drug concentration in tissues surrounding implants was much higher than that in blood which was still superior to the effective value to kill mycobacterium tuberculosis. MC3T3-E1 osteoblasts proliferated well in extracts and co-cultures on composite scaffolds, indicating good cytocompatibility and cell affinity of the scaffolds. The results of a rabbit radius repair experiment displayed that scaffolds have good bone regeneration capacity. The RFP-loaded b-PLGC/TCP composite scaffold thus could be envisioned to be a potential and promising substrate in clinical treatment of bone tuberculosis.

A biomimetic 3D microtubule-orientated poly(lactide-co-glycolide) scaffold with interconnected pores for tissue engineering.

An ideal tissue engineering scaffold should imitate physical and biochemical cues of natural extracellular matrix and have interconnected porous structures with high porosity to provide adequate space for cell seeding, growth and proliferation, as well as nutrient delivery and metabolized product elimination. In this study, we examined the feasibility of fabricating microtubule-orientated poly(lactide-co-glycolide) (PLGA) scaffolds with interconnected pores (denoted as MOIP-PLGA) by an improved thermal-induced phase separation technique. We successfully constructed MOIP-PLGA using 1,4-dioxane as the first solvent and benzene or water with lower freezing point as the second solvent. Especially, when water was used, the MOIP-PLGA had higher porosity and it could guide rabbit aortic smooth muscle cells (SMCs) to better grow along the microtubule direction of the scaffold. Comparing with microtubule-orientated scaffold without interconnected pores (denoted as MONIP-PLGA), the proliferation and viability of SMCs cultured on MOIP-PLGA were higher. Moreover, basic fibroblast growth factor could be effectively bound on MOIP-PLGA by a plasma treatment technique and the growth factor could be slowly released in vitro, maintaining bioactivity.

Effect of poly(DL-lactide-co-glycolide) on scar formation after glaucoma filtration surgery.

BACKGROUND: Glaucoma filtering surgery (GFS) is the most common procedure performed in the treatment of glaucoma. Although antiscarring agents help prevent postsurgical scarring and improve glaucoma surgical outcomes, they may be associated with an increased incidence of severe and potentially blinding complications. Poly(DL-lactide-co-glycolide) (PDLLA/GA) is a bioresorbable polymer, which can be prepared with a large range of physical, mechanical, and biological properties and has been widely used in medicine, including as an absorbable suture and a drug carrier and especially as a scaffold in tissue engineering. This study aimed to evaluate the effect of PDLLA/GA on scar formation after glaucoma filtration surgery (GFS). METHODS: Forty-eight New Zealand white rabbits were divided into two groups randomly and GFS was performed on the right eye of each. PDLLA/GA membranes were put under the sclera flap for evaluation. GFS with no membrane inserted served as control. Clinical evaluations of intraocular pressure (IOP) and the presence of a filtration bleb were performed at intervals (3 days, 1, 2, 4, 8, 12, 20, and 24 weeks) postoperatively. At each time point, three eyes per group were excised to observe histological changes such as inflammation and scar formation and the expression of collagen type IV, proliferating cell nuclear antigen (PCNA), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1). The expression of connective tissue growth factor (CTGF) mRNA was determined by reverse transcription-polymerase chain reaction. RESULTS: The lower IOP level and an effective bleb were maintained for a long time after GFS in the PDLLA/GA group. The histological analysis showed less inflammation and scar formation, weaker expression of collagen type IV and PCNA, more intense MMP-9 and TIMP-1, slightly elevated ratio of MMP-9 and TIMP-1, and a smaller increase in CTGF mRNA postoperatively in the PDLLA/GA group but less than the control group (P < 0.05). CONCLUSION: PDLLA/GA membranes may be promising for preventing fibrosis after GFS.

Co-transplantation of neural stem cells and Schwann cells within poly (L-lactic-co-glycolic acid) scaffolds facilitates axonal regeneration in hemisected rat spinal cord.

BACKGROUND: Various tissue engineering strategies have been developed to facilitate axonal regeneration after spinal cord injury. This study aimed to investigate whether neural stem cells (NSCs) could survive in poly(L-lactic-co-glycolic acid) (PLGA) scaffolds and, when cografted with Schwann cells (SCs), could be induced to differentiate towards neurons which form synaptic connection and eventually facilitate axonal regeneration and myelination and motor function. METHODS: NSCs and SCs which were seeded within the directional PLGA scaffolds were implanted in hemisected adult rat spinal cord. Control rats were similarly injured and implanted of scaffolds with or without NSCs. Survival, migration, differentiation, synaptic formation of NSCs, axonal regeneration and myelination and motor function were analyzed. Student's t test was used to determine differences in surviving percentage of NSCs. One-way analysis of variance (ANOVA) was used to determine the differences in the number of axons myelinated in the scaffolds, the mean latency and amplitude of cortical motor evoked potentials (CMEPs) and Basso, Beattie & Bresnahan locomotor rating scale (BBB) score. The χ(2) test was used to determine the differences in recovery percentage of CMEPs. RESULTS: NSCs survived, but the majority migrated into adjacent host cord and died mostly. Survival rate of NSCs with SCs was higher than that of NSCs without SCs ((1.7831 ± 0.0402)% vs. (1.4911 ± 0.0313)%, P < 0.001). Cografted with SCs, NSCs were induced to differentiate towards neurons and might form synaptic connection. The mean number of myelinated axons in PLGA + NSCs + SCs group was more than that in PLGA + NSCs group and in PLGA group ((110.25 ± 30.46) vs. (18.25 ± 3.30) and (11.25 ± 5.54), P < 0.01). The percentage of CMEPs recovery in PLGA + NSCs + SCs group was higher than in the other groups (84.8% vs. 50.0% and 37.5%, P < 0.05). The amplitude of CMEPs in PLGA + NSCs + SCs group was higher than in the other groups ((1452.63 ± 331.70) µV vs. (428.84 ± 193.01) µV and (117.33 ± 14.40) µV, P < 0.05). Ipsilateral retransection resulted in disappearance again and functional loss of CMEPs for a few days. But contralateral retransection completely damaged the bilateral motor function. CONCLUSIONS: NSCs can survive in PLGA scaffolds, and SCs promote NSCs to survive and differentiate towards neurons in vivo which even might form synaptic connection. The scaffolds seeded with cells facilitate axonal regeneration and myelination and motor function recovery. But regenerating axons have limited contribution to motor function recovery.

Osteocompatibility evaluation of poly(glycine ethyl ester-co-alanine ethyl ester)phosphazene with honeycomb-patterned surface topography.

Biodegradable amino acid ester-substituted polyphosphazenes are unique biomaterials for tissue engineering. Considering the surface properties as topography and chemical composition having vital roles in regulating cellular response, in this study, a kind of micropatterned polyphosphazene films were prepared and subjected to osteoblasts culture. Briefly, poly(glycine ethyl ester-co-alanine ethyl ester)phosphazene (PGAP) was synthesized, and its solution in chloroform was cast under high (80%) or low (20%) environmental humidity. Honeycomb-patterned or flat PGAP films were resulted. By analyzing with scanning electron microscope, atomic force microscope, X-ray photoelectron spectroscope, and water contact angle measurement, the honeycomb-patterned PGAP films demonstrated higher surface roughness, phosphorous and nitrogen content, and hydrophilicity than the flat one. Although the initial cell attachment and proliferation on PGAP films were inferior to those on conventional poly(lactic-co-glycolic acid) films, P-containing PGAP was a sort of bone-binding bioactive polymer. With these alternations, honeycomb-patterned PGAP films had accordingly enhanced protein adsorption and apatite deposition in simulated body fluid and showed great advantages in promoting osteogenous differentiation. The results suggested a potential way to make polyphosphazenes as good choices for bone tissue regeneration by increasing their surface roughness and phosphorous content.

Injectable hydrogel as stem cell scaffolds from the thermosensitive terpolymer of NIPAAm/AAc/HEMAPCL.

A series of biodegradable thermosensitive copolymers was synthesized by free radical polymerization with N-isopropylacrylamide (NIPAAm), acrylic acid (AAc) and macromer 2-hydroxylethyl methacrylate-poly(ɛ-caprolactone) (HEMAPCL). The structure and composition of the obtained terpolymers were confirmed by proton nuclear magnetic resonance spectroscopy, while their molecular weight was measured using gel permeation chromatography. The copolymers were dissolved in phosphate-buffered saline (PBS) solution (pH = 7.4) with different concentrations to prepare hydrogels. The lower critical solution temperature (LCST), cloud point, and rheological property of the hydrogels were determined by differential scanning calorimetry, ultraviolet-visible spectrometry, and rotational rheometry, respectively. It was found that LCST of the hydrogel increased significantly with the increasing NIPAAm content, and hydrogel with higher AAc/HEMAPCL ratio exhibited better storage modulus, water content, and injectability. The hydrogels were formed by maintaining the copolymer solution at 37°C. The degradation experiment on the formed hydrogels was conducted in PBS solution for 2 weeks and demonstrated a less than 20% weight loss. Scanning electron microscopy was also used to study the morphology of the hydrogel. The copolymer with NIPAAm/AAc/HEMAPCL ratio of 88:9.6:2.4 was bioconjugated with type I collagen for the purpose of biocompatibility enhancement. In-vitro cytotoxicity of the hydrogels both with and without collagen was also addressed.

The impact of PLGA scaffold orientation on in vitro cartilage regeneration.

The success of in vitro cartilage regeneration provides a promising approach for cartilage repair. However, the currently engineered cartilage in vitro is unsatisfactory for clinical application due to non-homogeneous structure, inadequate thickness, and poor mechanical property. It has been widely reported that orientation of scaffolds can promote cell migration and thus probably contributes to improving tissue regeneration. This study explored the impact of microtubular oriented scaffold on in vitro cartilage regeneration. Porcine articular chondrocytes were seeded into microtubule-oriented PLGA scaffolds and non-oriented scaffolds respectively. A long-term in vitro culture followed by a long-term in vivo implantation was performed to evaluate the influence of scaffold orientation on cartilage regeneration. The current results showed that the oriented scaffolds could efficiently promote cell migration towards the inner region of the constructs. After 12 weeks of in vitro culture, the chondrocyte-scaffold constructs in the oriented group formed thicker cartilage with more homogeneous structure, stronger mechanical property, and higher cartilage matrix content compared to the non-oriented group. Furthermore, the in vitro engineered cartilage based on oriented scaffolds showed better cartilage formation in terms of size, wet weight, and homogeneity after 12-week in vivo implantation in nude mice. These results indicated that the longitudinal microtubular orientation of scaffolds can efficiently improve the structure and function of in vitro engineered cartilage.

The effect of composition of calcium phosphate composite scaffolds on the formation of tooth tissue from human dental pulp stem cells.

Different approaches towards making 3-dimensional (3-D) bioengineered tooth for future replacement therapy have been developed including scaffold-based tooth regeneration. However, selection of optimal scaffold for future clinical application remains a challenge. In the present study, we tested biocompatibility of four different types of 3-D scaffolds for tooth-tissue regeneration, including a pure poly(lactide-co-glycolide) (PLGA) (70/30, mol/mol) scaffold and three types of calcium phosphate contained composites scaffolds that were 50 wt% of PLGA combined with 50 wt% of hydroxyapatite (HA), tricalcium phosphate (TCP) or calcium carbonate hydroxyapatite (CDHA) respectively. These scaffolds were fabricated by the particle leaching in combination with phase separation technology. Surface modification of these scaffolds was further performed by an ammonia plasma treatment and anchorage of collagen technology. Effect of composition of the composite scaffolds on proliferation of human dental pulp stem cells (DPSCs) was accessed using in vitro MTT assay and in vivo BrdU labeling. Differentiation capability of the DPSCs in the scaffolds was analyzed by measurement of the levels of calcified tissue formation and ALP activity. Our results showed that while the calcium phosphate contained compound is able to support regeneration of tooth tissue effectively, the PLGA/TCP scaffold is more appropriate for the proliferation and differentiation of DPSCs. Furthermore, seeding of dissociated 4-dpn rat tooth bud cells on the PLGA/TCP scaffold generated dentin- and pulp-like tissues. Our results demonstrate that the PLGA/TCP scaffold is superior to the other three scaffolds for tooth-tissue regeneration, especially for dentin formation.

Cell affinity for bFGF immobilized heparin-containing poly(lactide-co-glycolide) scaffolds.

In order to effectively and uniformly immobilize basic fibroblast growth factor (bFGF) to thick PLGA scaffold, the heparin-conjugated PLGA (H-PLGA) was synthesized at the first by reaction between heparin and a low molecular weight PLGA. Then heparin-containing PLGA (H-PLGA/PLGA) scaffold was fabricated by blending the H-PLGA with a high molecular weight PLGA. Finally, bFGF was immobilized on the H-PLGA/PLGA scaffold mainly by static electricity action between them. The effect of H-PLGA content on bFGF binding efficiency of the H-PLGA/PLGA scaffolds was investigated. It was found that bFGF binding efficiency increased with increasing H-PLGA content. The bound bFGF can release in vitro slowly from the H-PLGA/PLGA scaffolds and last over two weeks. The released bFGF has still preserved its bioactivity. The attachment and growth of mouse 3T3 fibroblasts on the H-PLGA/PLGA scaffolds were better than that on the PLGA scaffold, however bFGF immobilized H-PLGA/PLGA scaffolds showed much better cell affinity. Therefore, the method to use the H-PLGA/PLGA scaffold for immobilizing bFGF is not only effective for slow delivering bFGF with bioactivity, but also can be used for fabricating thick scaffold where bFGF could be combined and uniformly distributed.