Preparation of thermo-responsive drug-loaded nanofibrous films created by electrospinning

We prepared thermosensitive and biocompatible drug-loaded nanofibrous films by an electrospinning technique using a block copolymer, poly(N-isopropylacrylamide)-b-poly(l-lactide) (PNLA), and poly(l-lactide) (PLLA). The copolymer PNLA was synthesized by the radical polymerization of N-isopropylacrylamide (NIPAAm), followed by the ring-opening polymerization of l-lactide. The properties of PNIPAAm and PNLA were selectively discussed based on the results of NMR, FT-IR, GPC, and CA analyses. Because of the low molecular weight of PNIPAAm and PNLA and the hydrolysis of PNLA resulting from its hydrophilicity, these copolymers were inappropriate for electrospinning separately. Hence, a mixture of PNLA and PLLA was used to prepare electrospun nanofibrous films. SEM images of the PNLA/PLLA electrospun films showed that homogeneous fibres with smooth surfaces were obtained. In vitro release studies indicated that the drug-release rate of the PNLA/PLLA electrospun nanofibrous films can be adjusted by the content and molecular weight of PNLA and by the environmental temperature. The results demonstrate that electrospinning is a promising way to create stimuli-responsive fibrous films with potential applications in the design of controllable drug delivery systems.

Thermosensitive and biocompatible PNLA/PLLA drug-loaded nanofibrous films with different morphologies and controlled drug release behaviors by electrospinning technique.     

Polydopamine-modified poly(l-lactic acid) nanofiber scaffolds immobilized with an osteogenic growth peptide for bone tissue regeneration

It is highly desirable for bone tissue engineering scaffolds to have significant osteogenic properties and capability to improve cell growth and thus enhance bone regeneration. In this study, a poly(l-lactic acid) (PLLA) nanofiber scaffold-immobilized osteogenic growth peptide (OGP) was prepared via polydopamine (PDA) coating. X-ray photoelectron spectroscopy (XPS), contact angle measurement, and scanning electron microscopy (SEM) were used to determine the OGP immobilization, hydrophilicity and surface roughness of the samples. The SEM and fluorescence images demonstrate that the PLLA nanofiber scaffolds immobilized with the OGP have excellent cytocompatibility in terms of cell adhesion and proliferation. The ALP activity and the Runx2 and OPN expression results indicated that the PLLA nanofiber scaffolds immobilized with OGP significantly enhanced the osteogenic differentiation and calcium mineralization of hMSCs in vitro. A rat model of critical skull bone defect was selected to evaluate the bone formation capacity of the scaffolds. Micro CT analysis and histological results demonstrated that the PLLA scaffolds immobilized with OGP significantly promoted bone regeneration in critical-sized bone defects. This study verifies that the PLLA scaffold-immobilized OGP has significant potential in bone tissue engineering.

Polydopamine-modified PLLA nanofiber scaffolds immobilized with osteogenic growth peptide were designed and prepared for promoting bone formation.     

Design and in vitro/in vivo evaluations of a multiple-drug-containing gingiva disc for periodontotherapy

In the current work, we set out to develop and evaluate a gingiva disc of cellulose acetate phthalate and poloxamer F-127 for the simultaneous delivery of multiple drugs, namely minocycline, celecoxib, doxycycline hyclate, and simvastatin, to abolish infection, impede inflammation, avert collagen destruction, and promote alveolar bone regeneration, respectively. In vitro release studies revealed the sustained release profiles of the drugs for 12 h and that they were active against Staphylococcus aureus, Escherichia coli and Streptococcus mutans. The in vivo bioactivity levels of these drugs were assessed by comparing the number of colony forming units during different phases of a study on Wistar rats, and the results showed a reduction in the number of bacterial colonies with the applied formulation. A mucosal irritation study conducted on Wistar rat gingiva confirmed the non-irritancy of the optimal gingiva disc. Hence, this customized, non-invasive polymeric gingiva disc displaying a sustained release of drugs can be a useful tool to treat acute to moderate stages of periodontitis.

A gingiva disc of cellulose acetate phthalate and poloxaner F-127 was developed for the simultaneous delivery of multiple drugs, including minocycline, to promote alveolar bone regeneration by abolishing infection, impeding inflammation and averting collagen destruction.     

3D-printed composite scaffold with anti-infection and osteogenesis potential against infected bone defects

In the field of orthopedics, an infected bone defect is a refractory disease accompanied by bone infection and defects as well as aggravated circulation. There are currently no personalized scaffolds that can treat bone infections using local stable and sustained-release antibiotics while providing mechanical support and bone induction to promote bone repair in the process of absorption in vivo. In our previous study, rifampicin/moxifloxacin-poly lactic-co-glycolic acid (PLGA) microspheres were prepared and tested for sustained release and antibacterial activity. The composite scaffold of poly-l-lactic acid (PLLA)/Pearl had a positive effect on mechanics supports and promoted osteogenesis. Therefore, in this study, the personalized scaffolds of PLLA/Pearl were first prepared by 3D printing. Then, rifampicin/moxifloxacin-PLGA (RM-P) microspheres were loaded into the scaffold pores to prepare the PLLA/Pearl/RM-P scaffolds. In this in vitro study, we investigated the structural characteristics and cytocompatibility of 3D-printed composite scaffolds, which indicates the integrity of the components in the scaffolds. The PLLA/Pearl and PLLA/Pearl/RM-P composite scaffolds can promote adhesion, proliferation, and differentiation of human bone marrow mesenchymal stem cells. Moreover, a rabbit model of infected bone defects of the radius was established. PLLA, PLLA/Pearl, and PLLA/Pearl/RM-P scaffolds were implanted into the bone nidus. The therapeutic effect of the three scaffolds on the infected bone defects was evaluated through imaging and microbiological and histological analysis after surgery. Among the three scaffolds, only the PLLA/Pearl/RM-P scaffold had anti-infection and bone defect repair in vivo. 3D printing provides support for personalized scaffold structures, and composite materials ensure that the scaffolds exert anti-infection and bone repair effects. Our study suggests that the PLLA/Pearl/RM-P scaffold is a promising new material in the clinical treatment of infected bone defects.

Indication the mechanism of dual-functional scaffold in the treatment of infected bone defects.     

Electrospun porous poly(3-hydroxybutyrate-co-4-hydroxybutyrate)/lecithin scaffold for bone tissue engineering

Bone tissue engineering has emerged as a promising restorative strategy for bone reconstruction and bone defect repair. It is challenging to establish an appropriate scaffold with an excellent porous microstructure for bone defects and thereby promote bone repair. In this study, electrospinning as a simple and efficient technology was employed to fabricate a porous poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB) scaffold coated with lecithin. The morphology, phase composition, and physical properties of the electrospun P34HB/lec scaffold were characterized. Meanwhile, cellular behaviors of bone marrow mesenchymal stem cells (BMSCs), including proliferation, adhesion, migration, osteogenic differentiation, and related gene expression, were also investigated. Finally, a rat subcutaneous implant model and a calvarial defect model were used to evaluated the biocompatibility and effect of these scaffolds on bone repair, respectively. The in vitro results demonstrated that these electrospun fibers were interwoven with each other to form the porous P34HB/lec scaffold and the addition of lecithin improved the hydrophilicity of the pure P34HB scaffold, enhanced the efficiency of cell migration, and decreased inflammatory response. Furthermore, the in vivo results showed that P34HB/lec scaffold had excellent biocompatibility, improved the vascularization, and promoted the bone regeneration. All these results indicated that nanofibers of P34HB scaffolds in combination with the lecithin could exert a synergistic effect on promoting osteogenesis and regeneration of bone defects; thus, the P34HB scaffold with lecithin showed great application potential for bone tissue engineering.

An electrospun P34HB scaffold was prepared and coated with lecithin. As a scaffold for bone tissue engineering, the P34HB/lec scaffold could promote proliferation and osteogenesis of BMSCs in vitro, and also accelerate bone regeneration in vivo.     

Cell-loaded injectable gelatin/alginate/LAPONITE® nanocomposite hydrogel promotes bone healing in a critical-size rat calvarial defect model

Injectable hydrogels have long been gaining attention in the bone tissue engineering field owing to their ability to mix homogeneously with cells and therapeutic agents, minimally invasive administration, and seamless defect filling. Despite the advantages, the use of injectable hydrogels as cell delivery carriers is currently limited by the challenge of mimicking the natural microenvironment of the loaded cells, promoting cell proliferation, and enhancing bone regeneration. To overcome these problems, we aimed to develop an injectable and in situ-forming nanocomposite hydrogel composed of gelatin, alginate, and LAPONITE® to mimic the architecture and composition of the extracellular matrix. The encapsulated rat bone marrow mesenchymal stem cells (rBMSCs) survived in the nanocomposite hydrogel, and the gel promoted cell proliferation in vitro. Systematic in vivo research of the biomimetic hydrogel with or without cells was conducted in a critical-size (8 mm) rat bone defect model. The in vivo results proved that the hydrogel loaded with rBMSCs significantly promoted bone healing in rat calvarial defects, compared to the hydrogel without cells, and that the hydrogel did not provoked side effects on the recipients. Given these advantageous properties, the developed cell-loaded injectable nanocomposite hydrogel can greatly accelerate the bone healing in critical bone defects, thus providing a clinical potential candidate for orthopedic applications.

An injectable cell-laden nanocomposite hydrogel simulate natural ECM, promote cell proliferation, and accelerate bone healing of critical-size rat calvarial defects.     

Effects of orlistat, simvastatin, and orlistat + simvastatin in obese patients with hypercholesterolemia: a randomized, open-label trial

Background: Many obese patients have comorbidities that worsen their prognoses, particularly if hypercholesterolemia is present. In these patients, dietary restrictions are not sufficient to reduce hypercholesterolemia and lose body weight.Objective: This 1-year, single-center, randomized, open-label study assessed the effects of diet and exercise plus treatment with orlistat, simvastatin, and orlistat + simvastatin on lipid profile, body composition, and blood pressure in obese patients with hypercholesterolemia.Methods: Obese, normotensive patients with hypercholesterolemia aged > 45 years were eligible. Patients were prescribed a restricted-calorie diet and were randomized to receive orlistat 120 mg TID (group O), Simvastatin 20 mg/d (group S), or orlistat 120 mg TID plus simvastatin 20 mg/d (group OS) for 1 year. Serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), highdensity lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels; body mass index (BMI); waist-circumference reduction (WCR); body weight loss (BWL); and diastolic blood pressure (DBF) and systolic blood pressure (SBP) were measured at baseline and after 6 months and 1 year of treatment.Results: We enrolled 87 patients (45 women, 42 men; mean age, 55 years). Four patients dropped out due to nontransient adverse events. After 1 year of treatment, significant improvements were found in all measured parameters in all treatment groups versus baseline values, except for HDL-C in group O. Significant between-group differences at 1 year included the following: TC, LDL-C, and TG levels and BMI, WCR, and BWL were significantly decreased in group OS versus groups O and S; DBP was significantly decreased in group OS versus group O; SBP and DBF were significantly decreased in group OS versus group S. HDL-C was significantly increased in group OS but not in groups O and S. Five patients in group O and 1 patient in group OS experienced transient gastrointestinal adverse events.Conclusions: In this study population, all 3 treatments produced significant improvements in most measured parameters from baseline. The combination treatment showed significantly greater reductions in serum TC and LDL-C levels, BMI, WCR, and BWL than with either orlistat or simvastatin alone. Small but significant differences in blood pressure were found with combination treatment.     

Biomimetic peptide enriched nonwoven scaffolds promote calcium phosphate mineralisation

Cell-free translational strategies are needed to accelerate the repair of mineralised tissues, particularly large bone defects, using minimally invasive approaches. Regenerative bone scaffolds should ideally mimic aspects of the tissue''s ECM over multiple length scales and enable surgical handling and fixation during implantation in vivo. Leveraging the knowledge gained with bioactive self-assembling peptides (SAPs) and SAP-enriched electrospun fibres, we presented a cell free approach for promoting mineralisation via apatite deposition and crystal growth, in vitro, of SAP-enriched nonwoven scaffolds. The nonwoven scaffold was made by electrospinning poly(ε-caprolactone) (PCL) in the presence of either peptide P₁₁-4 (Ac-QQRFEWEFEQQ-Am) or P₁₁-8 (Ac QQRFOWOFEQQ-Am), in light of the polymer''s fibre forming capability and its hydrolytic degradability as well as the well-known apatite nucleating capability of SAPs. The 11-residue family of peptides (P₁₁-X) has the ability to self-assemble into β-sheet ordered structures at the nano-scale and to generate hydrogels at the macroscopic scale, some of which are capable of promoting biomineralisation due to their apatite-nucleating capability. Both variants of SAP-enriched nonwoven used in this study were proven to be biocompatible with murine fibroblasts and supported nucleation and growth of apatite minerals in simulated body fluid (SBF) in vitro. The fibrous nonwoven provided a structurally robust scaffold, with the capability to control SAP release behaviour. Up to 75% of P₁₁-4 and 45% of P₁₁-8 were retained in the fibres after 7 day incubation in aqueous solution at pH 7.4. The encapsulation of SAP in a nonwoven system with apatite-forming as well as localised and long-term SAP delivery capabilities is appealing as a potential means of achieving cost-effective bone repair therapy for critical size defects.

A structurally robust electrospun peptide-enriched scaffold, with controlled peptide release behaviour, supports nucleation and growth of hydroxyapatite minerals in vitro.     

Novel electrospun fibers as carriers for delivering a biocompatible Sm(iii) nanodrug for cancer therapy: fabrication,characterization, cytotoxicity and toxicity

The current study represents the successful fabrication and characterization of a Sm(iii) nano complex based on 2-cyano-N′-((4-oxo-4H-chromen-3-yl)methylene)acetohydrazide (CCMA). The fibrous Sm(iii) nanocomplex has been fabricated by the electrospinning technique. SEM analysis of the electrospun fibers has revealed that the fibers have a uniform structure and smooth surface without observing Sm(iii) nanocomplex crystals, i.e. the Sm(iii) nanocomplex has been well incorporated into the fibers. In vitro antitumor activity against two carcinogenic cell lines (HepG-2 and E.A.C.) as well as in vivo toxicity of pure Sm(iii) nanocomplex and its electrospun fibers have been detected. The biological results have shown that there is a significant antitumor activity with low toxicity of the pure Sm(iii) nanocomplex and its electrospun fibers with respect to different standard antitumor drugs. Also, the electrospun fibers recorded higher cytotoxicity (IC₅₀ = 0.1 μM (Hep-G); 0.09 μM (E.A.C)) and lower toxicity (LD₅₀ = 350 mg kg⁻¹) than the pure ones. The in vitro release rate of the Sm(iii) nanocomplex from electrospun fibers has also been detected. The results have shown that the burst releasing of the Sm(iii) nanocomplex is about 22% after 1 h at the beginning, then a cumulative release increased gradually over the following hours. All results demonstrate the potential use of the Sm(iii) nanocomplex as a potent antitumor drug and its electrospun fibers as superior drug carriers for the treatment of tumors.

The current study represents the successful fabrication and characterization of a Sm(iii) nano complex based on 2-cyano-N′-((4-oxo-4H-chromen-3-yl)methylene)acetohydrazide (CCMA).     

Modifying collagen with alendronate sodium for bone regeneration applications

Phosphorylated materials are attractive candidates for bone regeneration because they may facilitate the construction of a phosphorylated bone extracellular matrix (ECM) to build a beneficial environment for bone formation. Here, we designed and synthesized a new phosphorylated material, collagen type I phosphorylated with alendronate sodium (Col-Aln), based on the biodegradable osteoconductive collagen backbone. Col-Aln can distinctly accelerate in vitro mineralization in simulated body fluid. Col-Aln showed good biocompatibility with bone marrow mesenchymal stem cells (BMSCs) and promoted their adhesion as well as the osteogenic differentiation of BMSCs more effectively than did pure collagen. Furthermore, collagen and Col-Aln scaffolds implanted into a critical-sized rat cranial defect for 4 and 8 weeks were shown to degrade in vivo and helped to facilitate bone growth in the defect, while the phosphate-containing Col-Aln scaffold significantly promoted new bone formation. Col-Aln provides a new strategy to integrate bioactive phosphate molecules via covalent grafting onto biopolymers and has promise for bone regeneration applications.

Efficient covalent bonding with phosphate-containing alendronate prompts the fast mineralization and osteoinduction of the collagen scaffold.     

The effectiveness of the controlled release of simvastatin from β‐TCP macrosphere in the treatment of OVX mice

Simvastatin, a cholesterol treatment drug, has been shown to stimulate bone regeneration. As such, there has been an increase interest in the development of suitable materials and systems for the delivery of simvastatin. Without the appropriate dosage of simvastatin, the therapeutic effects on bone growth will be significantly reduced. Furthermore, similar to many pharmaceutical compounds, at high concentration simvastatin can cause various adverse side‐effects. Given the associated side‐effects with the usage of simvastatin, the development of suitable controlled drug release system is pertinent. Calcium phosphate in particularly beta‐tricalcium phosphate (β‐TCP) has been extensively studied and used as a carrier material for drug delivery system. In this study, Foraminifera exoskeletons were used as calcium carbonate precursor materials, which were hydrothermally converted to β‐TCP as a carrier material for simvastatin. Natural marine exoskeletons posses interconnected and uniformly porous network capable of improving drug loading and release rate. To prolong the r elease of simvastatin, an apatite coating was made around the β‐TCP sample and in vitro release studies in simulated body fluid (SBF) showed a significant decrease in release rate. Osteoporotic mice were used to examine the compare therapeutic effectiveness of β‐TCP, β‐TCP with simvastatin, apatite‐coated β‐TCP with simvastatin and direct injection of simvastatin near the right femur of the mice. Localized and systemic effect were compared with the femur of the non‐implanted side (left) and showed that β‐TCP with or without simvastatin was able to induce significant bone formation over 6 weeks. Mechanical analysis showed that apatite‐coated β‐TCP with simvastatin produced significantly stronger bones compared with other experimental groups. This study shows that natural exoskeletons with the appropriate structure can be successfully used as a drug delivery system for simvastatin and can its release can be prolonged with an apatite coating to significantly promote relevant bone formation. Copyright © 2013 John Wiley & Sons, Ltd.     

Local delivery of a novel PTHrP via mesoporous bioactive glass scaffolds to improve bone regeneration in a rat posterolateral spinal fusion model

With the development of tissue engineering, bone defects, such as fractured long bones or cavitary lesions, may be efficiently repaired and reconstructed using bone substitutes. However, high rates of fusion failure remain unavoidable in spinal fusion surgery owing to the lack of appropriate materials for bone regeneration under such challenging conditions. Parathyroid hormone (PTH), a major regulator of bone remodeling, exerts both anabolic and catabolic effects. In this study, we modified PTH(1–34) and designed and synthesized a novel PTH-related peptide, namely PTHrP-1. Further, we fabricated a local PTHrP delivery device from mesoporous bioactive glass (MBG) to address the need for a suitable material in spinal fusion surgery. Using MBG scaffolds as a control, the biological properties of PTHrP-MBG scaffolds were evaluated in terms of attachment, proliferation, and alkaline phosphatase activity, as well as osteogenic gene and angiogenic gene expression in co-cultured rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. Furthermore, PTHrP-1-MBG scaffolds were tested in a rat posterolateral spinal fusion model. Our data showed that PTHrP-1-MBG scaffolds possessed good ability to facilitate attachment and stimulation of rBMSC proliferation and differentiation. Importantly, the in vivo results revealed that the PTHrP-1-MBG scaffolds facilitated faster new bone formation and a higher rate and quality of spinal fusion. Therefore, the results suggest that devices consisting of the present novel PTHrP and MBG possess wider potential applications in bone regeneration and should serve as a promising bone substitute for spinal fusion.

With the development of tissue engineering, bone defects, such as fractured long bones or cavitary lesions, may be efficiently repaired and reconstructed using bone substitutes.     

Novel naturally crosslinked electrospun nanofibrous chitosan mats for guided bone regeneration membranes: material characterization and cytocompatibility

Guided bone regeneration (GBR) barrier membranes are used to prevent soft tissue infiltration into the graft space during dental procedures that involve bone grafting. Chitosan materials have shown promise as GBR barrier membranes, due to their biocompatibility and predictable biodegradability, but degradation rates may still be too high for clinical applications. In this study, chitosan GBR membranes were electrospun using chitosan (70% deacetylated, 312 kDa, 5.5 w/v%), with or without the addition of 5 or 10 mm genipin, a natural crosslinking agent, in order to extend the degradation to meet the clinical target time frame of 4–6 months. Membranes were evaluated for fibre diameter, tensile strength, biodegradation rate, bond structure and cytocompatibility. Genipin addition, at 5 or 10 mm , resulted in median fibre diameters 184, 144 and 154 nm for uncrosslinked, 5 mm and 10 mm crosslinked, respectively. Crosslinking, examined by Fourier transform infrared spectroscopy, showed a decrease in N–H stretch as genipin levels were increased. Genipin‐crosslinked mats exhibited only 22% degradation based on mass loss, as compared to 34% for uncrosslinked mats at 16 weeks in vitro. The ultimate tensile strength of the mats was increased by 165% to 32 MPa with 10 mm crosslinking as compared to the uncrosslinked mats. Finally, genipin‐crosslinked mats supported the proliferation of SAOS‐2 cells in a 5 day growth study, similar to uncrosslinked mats. These results suggest that electrospun chitosan mats may benefit from genipin crosslinking and have the potential to meet clinical degradation time frames for GBR applications. Copyright © 2012 John Wiley & Sons, Ltd.     

Enhancement of neural stem cell survival,proliferation and differentiation by IGF-1 delivery in graphene oxide-incorporated PLGA electrospun nanofibrous mats

The mammalian central nervous system has a limited ability for self-repair under injury conditions. The treatment of nerve injuries has been revolutionised with the development of tissue engineering techniques. However, the lack of bioactivity has severely restricted the application of biodegradable implants for neurogenesis. Therefore, surface modification of biomaterials is crucial to improve their bioactivity and promote endogenous repair mechanisms for nerve regeneration. Insulin-like growth factor 1 (IGF-1) is a growth factor for neuroprotection and neurogenesis. In this study, IGF-1 was successfully immobilised on graphene oxide (GO)-incorporated poly(lactic-co-glycolic acid) (PLGA) biodegradable electrospun nanofibres. For the in vitro investigation, neural stem cells (NSCs) were cultured on different nanofibres to observe various cellular activities. GO enhanced NSC survival under H₂O₂ pre-treatment and neuronal differentiation to some extent. More importantly, the immobilisation of IGF-1 onto the PLGA/GO nanofibres resulted in significantly increased NSC survival, proliferation, and differentiation. Findings from this study revealed that using PLGA/GO electrospun nanofibres to immobilise IGF-1 has excellent potential for the enhancement of the neuroprotective and neurogenic effects of nerve implants.

The mammalian central nervous system has a limited ability for self-repair under injury conditions.     

A three-dimensional hydroxyapatite/polyacrylonitrile composite scaffold designed for bone tissue engineering

In recent years, various composite scaffolds based on hydroxyapatite have been developed for bone tissue engineering. However, the poor cell survival micro-environment is still the major problem limiting their practical applications in bone repairing and regeneration. In this study, we fabricated a class of fluffy and porous three-dimensional composite fibrous scaffolds consisting of hydroxyapatite and polyacrylonitrile by employing an improved electrospinning technique combined with a bio-mineralization process. The fluffy structure of the hydroxyapatite/polyacrylonitrile composite scaffold ensured the cells would enter the interior of the scaffold and achieve a three-dimensional cell culture. Bone marrow mesenchymal stem cells were seeded into the scaffolds and cultured for 21 days in vitro to evaluate the response of cellular morphology and biochemical activities. The results indicated that the bone marrow mesenchymal stem cells showed higher degrees of growth, osteogenic differentiation and mineralization than those cultured on the two-dimensional hydroxyapatite/polyacrylonitrile composite membranes. The obtained results strongly supported the fact that the novel three-dimensional fluffy hydroxyapatite/polyacrylonitrile composite scaffold had potential application in the field of bone tissue engineering.

A fluffy and porous (3D) HA composite fibrous scaffold was fabricated by employing an improved electrospinning technique combined with a bio-mineralization process.     

Sintered porous Ti6Al4V scaffolds incorporated with recombinant human bone morphogenetic protein-2 microspheres and thermosensitive hydrogels can enhance bone regeneration

A well-controlled powder sintering technique was used to fabricate porous Ti6Al4V scaffold. The thermosensitive chitosan thioglycolic acid (CS-TA) hydrogel was used as a carrier to inject recombinant human bone morphogenetic protein-2 (rhBMP-2) microspheres into pores of the Ti6Al4V scaffold at 37 °C, and then the porous Ti6Al4V/rhBMP-2 loaded hydrogel composite was obtained. The bare Ti6Al4V scaffold was used as the control. The characteristics and mechanical properties of the scaffold, rheological properties of the hydrogels and the rhBMP-2 loaded hydrogel, the release of the rhBMP-2 loaded hydrogel, and the biological properties of the two types of samples were evaluated by in vitro and in vivo tests. Results indicated that the sintered porous Ti6Al4V had high porosity, large pore size with good mechanical properties. The hydrogel and rhBMP-2 loaded hydrogel showed thermosensity. The rhBMP-2 loaded hydrogel showed a stable and extended release profile without too high burst release of rhBMP-2. Both groups showed good biocompatibility and osteogenic ability. However, according to the results of cell tests and implantation, the group with rhBMP-2 loaded hydrogel had significantly higher cell proliferation rate, faster bone growth speed, and more bone ingrowth at every time point. Therefore, the sintered porous Ti6Al4V scaffolds incorporated with rhBMP-2 microspheres and CS-TA hydrogel was effective in enhancing the bone regeneration, and prospects a good candidate for application in orthopedics.

Porous Ti6Al4V scaffolds incorporated with rhBMP-2 microspheres and CS-TA hydrogel can enhance the bone regeneration.     

Preparation and characterization of antibacterial dopamine-functionalized reduced graphene oxide/PLLA composite nanofibers

Electrospun poly(l)-lactide (PLLA) ultrafine fibers are a biodegradable and biocompatible scaffold, widely used in tissue engineering applications. Unfortunately, these scaffolds have some limitations related to the absence of bioactivity and antibacterial capacity. In this study, dopamine-functionalized reduced graphene oxide (rGO)/PLLA composite nanofibers were fabricated via electrospinning. The morphology and the physicochemical and biological properties of the composite nanofibers were investigated. The results indicate that incorporating rGO improves the hydrophilic, mechanical, and biocompatibility properties of PLLA nanofibers. Tetracycline hydrochloride (TC)-loaded rGO/PLLA composite nanofibers showed better controlled drug release profiles compared to GO/PLLA and PLLA nanofibrous scaffolds. Drug-loaded nanofibrous scaffolds showed significantly improved antibacterial activity against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). Additionally, rGO/PLLA composite nanofibers exhibited enhanced cytocompatibility. Thus, it can be concluded that rGO/PLLA composite nanofibers allow the development of multifunctional scaffolds for use in biomedical applications.

Antibacterial dopamine-functionalized reduced graphene oxide (rGO)/PLLA composite nanofibers for biomedical applications.     

Comparative study of NMP‐preloaded and dip‐loaded membranes for guided bone regeneration of rabbit cranial defects

Guided bone regeneration (GBR) has been utilized for several decades for the healing of cranio‐maxillofacial bone defects and, particularly in the dental field, by creating space with a barrier membrane to exclude soft tissue and encourage bone growth in the membrane‐protected volume. Although the first membranes were non‐resorbable, a new generation of GBR membranes aims to biodegrade and provide bioactivity for better overall results. The Inion GTR? poly(lactide‐co‐glycolide) (PLGA) membrane is not only resorbable but also bioactive, since it includes N‐methylpyrrolidone (NMP), which has been shown to promote bone regeneration. In this study, the effects of loading different amounts of NMP onto the membrane through chemical vapour deposition or dipping have been explored. In vitro release demonstrated that lower levels of NMP led to lower NMP concentrations and slower release, based on total NMP loaded in the membrane. The dipped membrane released almost all of the NMP within 15 min, leading to a high NMP concentration. For the in vivo studies in rabbits, 6 mm calvarial defects were created and left untreated or covered with an ePTFE membrane or PLGA membranes dipped in, or preloaded with, NMP. Evaluation of the bony regeneration revealed that the barrier membranes improved bony healing and that a decrease in NMP content improved the performance. Overall, we have demonstrated the potential of these PLGA membranes with a more favourable NMP release profile and the significance of exploring the effect of NMP on these PLGA membranes with regard to bone ingrowth. Copyright © 2014 John Wiley & Sons, Ltd.     

Electrospun collagen core/poly-l-lactic acid shell nanofibers for prolonged release of hydrophilic drug

The development of sustained control drug release for delivering hydrophilic drugs has been challenging due to a burst release. Nanofibers are used as materials that enable efficient drug delivery systems. In this study, we designed drug-encapsulated core–shell nanofibers comprising a hydrophilic core of collagen (Col) incorporated with berberine chloride (BC), an anti-inflammatory and anti-cancer agent used as a model drug, and a hydrophobic shell of poly-l-lactic acid (PLLA). Long-term drug release profiles under both the physiological and hydrolysis-accelerated conditions were measured and analyzed using a Korsmeyer–Peppas kinetics model. We found that the Col/PLLA core–shell fiber achieved a controllable long-term release of the hydrophilic drug incorporated inside the core by the slow degradation of the PLLA shell to prevent the burst release while PLLA monolithic fibers showed early release due to the dissolution of drug and the following rapid hydrolysis of fibers. As shown by the results of Col/PLLA core–shell fiber under a hydrolysis-accelerated condition to promote the release of drugs test, it would provide sustained release over 16 days under physiological conditions. Here, the development of the nanomaterial for the long-term drug release of hydrophilic drugs was achieved, leading to its potential medical application including cancer treatment.

A hydrophilic drug was encapsulated in nanofibers with hydrophobic shell using core–shell electrospinning. Drug–polymer miscibility affected the crystallinity of drug-loaded nanofibers. Our results propose a way to prolong the release of hydrophilic drugs from nanofibers.