Poly(lactic-co-glycolic) Acid Microspheres Research Articles

Fabrication of stem cell heterospheroids with sustained-release chitosan and poly(lactic-co-glycolic acid) microspheres to guide cell fate toward chondrogenic differentiation

Mesenchymal stem cell (MSC)-based therapies show great potential in treating various diseases. However, control of the fate of injected cells needs to be improved. In this work, we developed an efficient methodology for modulating chondrogenic differentiation of MSCs. We fabricated heterospheroids with two sustained-release depots, a quaternized chitosan microsphere (QCS-MP) and a poly (lactic-co-glycolic acid) microsphere (PLGA-MP). The results show that heterospheroids composed of 1 × 104 to 5 × 104 MSCs formed rapidly during incubation in methylcellulose medium and maintained high cell viability in long-term culture. The MPs were uniformly distributed in the heterospheroids, as shown by confocal laser scanning microscopy. Incorporation of transforming growth factor beta 3 into QCS-MPs and of dexamethasone into PLGA-MPs significantly promoted the expression of chondrogenic genes and high accumulation of glycosaminoglycan in heterospheroids. Changes in crucial metabolites in the dual drug depot–engineered heterospheroids were also evaluated using 1H NMR-based metabolomics analysis to verify their successful chondrogenic differentiation. Our heterospheroid fabrication platform could be used in tissue engineering to study the effects of various therapeutic agents on stem cell fate.

Microfluidics-derived hierarchical microparticles for the delivery of dienogest for localized endometriosis therapy

Drug therapy is one of the most important strategies for treating gynecological diseases. Local drug delivery is promising for achieving optimal regional drug exposure, considering the complex anatomy and dynamic environment of the upper genital tract. Here, we present microparticle-based microcarriers with a hierarchical structure for localized dienogest (DNG) delivery and endometriosis treatment. The microparticles were fabricated by microfluidics and consisted of photo-crosslinked bovine serum albumin hydrogel particles (D@P-B MPs) encapsulating DNG-loaded PLGA (poly lactic-co-glycolic acid) microspheres. Such design enables the microparticles to have sustained release capacity and cell adhesion ability. Based on this, the microparticles were applied for the treatment of peritoneal endometriosis through intraperitoneal injection. The performance of the microparticles in inhibiting the growth of ectopic lesions as well as their anti-inflammatory, anti-angiogenesis, and pelvic pain-relieving effects are well demonstrated in vivo. These findings indicate that the present hierarchical microparticles are good candidates for localized treatment of endometriosis and are promising for the management of gynecological diseases. STATEMENT OF SIGNIFICANCE: We prepared photo-crosslinked bovine serum albumin hydrogel particles (D@P-B MPs) encapsulating DNG-loaded PLGA microspheres using microfluidic electrospray. Such hierarchical structure provided multiple functions of the particles as drug carriers. The hierarchical microparticles not only supported the sustained release of drugs but also provided adhesion to human ectopic endometrial stromal cells. The hierarchical microparticles represented a localized treatment method for endometriosis and is promising for the management of gynecological diseases.

DNA vaccine incorporated poly (lactic-co-glycolic) acid (PLGA) microspheres offer enhanced protection against Aeromonas hydrophila infection

Encapsulation of DNA vaccines onto carriers enhances the immunogenicity of an antigen. Specifically, biodegradable polymers offer sustained release of vaccines which is crucial for any targeted delivery approach. Poly (lactic-co-glycolic) acid (PLGA) microspheres were used to load a DNA vaccine having a targeted gene of outer membrane protein (OMP) of Aeromonas hydrophila to clone and construct a DNA vaccine using a eukaryotic expression vector system (pVAX1-OMP DNA) and delivery in Carassius auratus against A. hydrophila infection. PLGA microspheres were prepared by emulsion technique oil-in-water and characterized by a High-Resolution Scanning Electron Microscope (HR-SEM). The results of PLGA-pVAX1-OMP DNA microspheres shows that average of 100–150 μm particle size and a loading efficiency (LE) of 68.8 %. Results indicate that C. auratus fed with PLGA-pVAX1-OMP DNA microspheres revealed a significant improvement in innate immune response, which includes, myeloperoxidase activity, respiratory burst and total immunoglobulin level compared with control group fish. The immune-related gene, IL1β, IL10, TGF, c-type, and g-type lysozyme also showed significantly higher expression after immunization. Furthermore, dietary supplementation of the PLGA-pVAX1-OMP DNA (G III) group exhibited a significantly higher survival rate (78 %) than the control group of fish. These results help us to understand the of mechanism of DNA vaccine administrated feed through PLGA nanoparticles resistance to infection by regulating systemic and innate immunity in Carassius auratus.

NMR relaxation and diffusion studies to probe the motional dynamics of risperidone within PLGA microsphere

The present study aims to investigate the motional dynamics of risperidone within polylactic co-glycolic acid (PLGA) microsphere by employing solution state 1H and 19F nuclear magnetic resonance (NMR) measurements. Risperidone, a second-generation fluorinated antipsychotic drug used for the treatment of schizophrenia is commercially marketed as PLGA microsphere formulation resulting in prolonged release of the drug in solution. Although the current trend in the pharmaceutical market is to develop drug formulation with long-acting release (LAR) products, complete physicochemical characterization of such formulations are scarce. Especially the effects of microsphere encapsulation on the motional properties and diffusion behavior of the drugs are not discussed adequately in any of the earlier reports. We therefore, have employed NMR relaxation and diffusion measurements to decipher the interaction of PLGA cavity water with risperidone. A detailed analysis of NMR relaxation rates confirmed the event of encapsulation and the presence of local motion in the non-fluorinated end of risperidone. Further, the relaxation data indicated a significant alteration in 19F chemical shift anisotropy (CSA) and CSA/dipole-dipole (DD) cross-correlated relaxation mechanism and decreased effect of solvent relaxation pointing out reduced water concentration within the microsphere cavity. 1H and 19F diffusion coefficients of risperidone led to the information about hydrodynamic radius of risperidone in free and encapsulated states. Measurement of hydrodynamic radius supported the presence of limited water in PLGA cavity allowing higher translational mobility of risperidone after the encapsulation.

Hierarchically porous calcium phosphate scaffold with degradable PLGA microsphere network

Calcium phosphate cement (CPC) is widely used in orthopedics, dentistry and spine surgery because of its excellent biocompatibility, osteoconductivity, arbitrary shaping and self-setting ability. However, slow degradation rate of CPC decreases its bone regeneration efficacy. Herein, poly (lactic co-glycolic acid) microspheres (PLGAm) and wollastonite (WS) were mixed with CPC powder to prepare CPC composite pastes, and then the composite pastes were perfused into poly (lactic co-glycolic acid) network (PLGAnw) to construct composite bone repair materials. The degradation of PLGAnw generated interconnected macropores with the short side of about 468 μm along horizontal axis and the long side of about 785 μm along longitudinal axis, while PLGAm degradation generated isolated or partially connected relative smaller spherical macropores with the size range of 53–106 μm and 106–150 μm, respectively, which was same with PLGAm; in addition, CPC formed micro/nano pores after hydration, thus constructing in-situ hierarchically porous CPC composite scaffolds. Meanwhile, PLGAnw and PLGAm also significantly promoted the degradation of CPC due to the release of acidic by-products. Therefore, the introduction of PLGA network and microspheres not only can evidently accelerate degradation of CPC, but also in-situ form connected macropores and hierarchically porous after their degradation, which are expected to improve bone repair effect of CPC.

Novel, Blended Polymeric Microspheres for the Controlled Release of Methotrexate: Characterization and In Vivo Antifibrotic Studies

Low dose methotrexate (MTX) is known to effectively decrease type I collagen production in dermal fibroblasts, while increasing the matrix metalloproteinase-1 (MMP-1) production in vitro. For in vivo use as an antifibrotic agent on wounds, a linear and extended controlled release formulation of MTX is required. The objective of this study was to optimize the fabrication of MTX-loaded polymeric microspheres with such properties, and to test the efficacy for the prevention of fibrosis in vivo. Poly lactic-co-glycolic acid (PLGA), Poly (L-lactic acid) (PLLA) and the diblock copolymer, methoxypolyethylene glycol-block-poly (D, L-lactide) (MePEG-b-PDLLA), were used to fabricate microspheres, which were then characterized in terms of size, drug encapsulation efficiency, and in vitro release profiles. The optimized formulation (PLGA with diblock copolymer) showed high drug encapsulation efficiency (>80%), low burst release (~10%) and a gradual release of MTX. The amphipathic diblock copolymer is known to render the microsphere surface more biocompatible. In vivo, these microspheres were effective in reducing fibrotic tissue which was confirmed by quantitative measurement of type I collagen and α-smooth muscle actin expression, demonstrating that MTX can be efficiently encapsulated in PLGA microspheres to provide a delayed, gradual release in wound beds to reduce fibrosis in vivo.

Photo-click crosslinked hydrogel containing MgO2-loaded PLGA microsphere with concurrent magnesium and oxygen release for bone tissue engineering

Overcoming hypoxia and providing a proper microenvironment for osteogenic differentiation are the most critical challenges in bone tissue engineering (BTE). Hydrogels with the capability to release oxygen and magnesium ions are considered to be a promising approach for BTE. Here, MgO2-loaded polylactic-co-glycolic acid (PLGA) microspheres were prepared to improve oxygen release, magnesium release, and pH control. Then, PLGA/MgO2 microspheres-loaded thiolated alginate (AlgT)/gelatin methacryloyl (GelMA) photocrosslinkable hydrogel was prepared using click reaction, and the effect of different concentrations of AlgT on the physical and chemical properties of the hydrogel was investigated. The pore size decreased as AlgT concentration increased from 101.11 ± 26.04 to 74.48 ± 14.03 μm, and the swelling ratio, elastic modulus, and compressive strength were increased when AlgT concentration increased from 821.30 ± 30% to 950 ± 60%, 0.69–1.23 MPa and 1.293–2.81 MPa, respectively. Pore size, swelling ratio, elastic modulus, and compressive strength were 88.28 ± 20 μm, 522.82 ± 29%, 1.64 ± 0.04 MPa, and 4.044 ± 0.041 MPa for microsphere-loaded hydrogel, respectively. Besides, the level of released magnesium and oxygen during 14 days ranged from 13 to 22 mg/L and 7.7–8.2 mg/L, respectively. The MTT and live/dead assay results showed suitable cell viability and adhesion on the microsphere-loaded hydrogels. Also, the calcium content and alkaline phosphatase activity of human Adipose-derived mesenchymal stem cells (hAMSCs) cultured on samples were investigated. Moreover, hAMSCs indicated osteogenic differentiation after 21 days in culture, including the expression of significant alkaline phosphatase, osteocalcin, and osteopontin. This study's results indicate the prepared hydrogels' suitability for osteogenic differentiation and bone tissue engineering.

Prolongation of Fate of Bacteriophages In Vivo by Polylactic-Co-Glycolic-Acid/Alginate-Composite Encapsulation.

With concern growing over antibiotics resistance, the use of bacteriophages to combat resistant bacteria has been suggested as an alternative strategy with which to enable the selective control of targeted pathogens. One major challenge that restrains the therapeutic application of bacteriophages as antibacterial agents is their short lifespan, which limits their antibacterial effect in vivo. Here, we developed a polylactic-co-glycolic acid (PLGA)/alginate-composite microsphere for increasing the lifespan of bacteriophages in vivo. The alginate matrix in PLGA microspheres encapsulated the bacteriophages and protected them against destabilization by an organic solvent. Encapsulated bacteriophages were detected in the tissue for 28 days post-administration, while the bacteriophages administered without advanced encapsulation survived in vivo for only 3–5 days. The bacteriophages with extended fate showed prophylaxis against the bacterial pathogens for 28 days post-administration. This enhanced prophylaxis is presumed to have originated from the diminished immune response against these encapsulated bacteriophages because of their controlled release. Collectively, composite encapsulation has prophylactic potential against bacterial pathogens that threaten food safety and public health.

The antimicrobial effects of PLGA microspheres containing the antimicrobial peptide OP-145 on clinically isolated pathogens in bone infections

Infection after fracture is a significant problem for the healing of fractures. Antimicrobial peptides combined with PLGA (poly-lactic-co-glycolic acid) microspheres can open new horizons for treating bone infections. Twenty rats in the control group were treated with physiologic saline solution after surgery, and 20 rats in the treatment group were treated with OP-145 PLGA microspheres and vancomycin after surgery. The biofilms from treatment and control groups were analyzed by fluorescence microscopy. Blood samples were collected at 12, 24, 36, 48, and 72 h. OP-145 PLGA microspheres showed significant inhibitory effects on clinically isolated strains (P < 0.05) and there were significant differences in serum CRP (P < 0.05) levels compared with control group. In conclusion, OP-145 PLGA microspheres could slowly release antimicrobial peptides and significantly reduce biofilm formation and levels of inflammatory factors.

The Evaluation of Bone Regeneration Following Socket Preservation with Concentrated Growth Factor (CGF) and Poly Lactic-Co-Glycolic Acid (PLGA) Scaffold in Rabbits

Various grafting materials are utilised to facilitate regeneration. There is currently a paradigm shift towards applying poly lactic-co-glycolic acid (PLGA), which is regarded as an excellent scaffold for tissue engineering. Concentrated growth factor (CGF) has also been reported to promote wound healing. Nevertheless, the role of PLGA microspheres as a substitute for bone graft material with CGF in bone regeneration remains unclear. This study was designed to evaluate the effect of CGF with PLGA on bone formation and the expression of alkaline phosphatase (ALP) following socket preservation. PLGA microspheres were prepared using double solvent evaporation method and observed under scanning electron microscopy (SEM). A 6 mL of rabbit’s blood was collected from the marginal ear vein and centrifuged to obtain CGF. Blood was also collected for ALP assessment from 24 New Zealand White (NZW) male rabbits subjected to the first upper left premolar extraction. Sockets were filled with CGF, PLGA, CGF+PLGA or left empty and observed with microscopic computed tomography (micro-CT) at four weeks and eight weeks. The SEM image revealed a spherical shape with interconnected pores on the surface of the PLGA particles. Repeated measures ANOVA were used to evaluate the effect of time and treatment (p &lt; 0.05) with significant differences in bone width, height, volume, volume fraction and expression of ALP was observed with CGF+PLGA. Both CGF and PLGA have the potential as the alternative grafting materials and this study could serve as an ideal benchmark for future investigations on the role of CGF+PLGA in bone regeneration enhancement.

Mimicking chronic glaucoma over 6 months with a single intracameral injection of dexamethasone/fibronectin-loaded PLGA microspheres

To create a chronic glaucoma animal model by a single intracameral injection of biodegradable poly lactic-co-glycolic acid (PLGA) microspheres (Ms) co-loaded with dexamethasone and fibronectin (MsDexaFibro). MsDexaFibro were prepared by a water-in-oil-in-water emulsion method including dexamethasone in the organic phase and fibronectin in the inner aqueous phase. To create the chronic glaucoma model, an interventionist and longitudinal animal study was performed using forty-five Long Evans rats (4-week-old). Rats received a single intracameral injection of MsDexafibro suspension (10%w/v) in the right eye. Ophthalmological parameters such as clinical signs, intraocular pressure (IOP), neuro-retinal functionality by electroretinography (ERG), retinal structural analysis by optical coherence tomography (OCT), and histology were evaluated up to six months. According to the results obtained, the model proposed was able to induce IOP increasing in both eyes over the study, higher in the injected eyes up to 6 weeks (p < 0.05), while preserving the ocular surface. OCT quantified progressive neuro-retinal degeneration (mainly in the retinal nerve fiber layer) in both eyes but higher in the injected eye. Ganglion cell functionality decreased in injected eyes, thus smaller amplitudes in PhNR were detected by ERG. In conclusion, a new chronic glaucoma animal model was created by a single injection of MsDexaFibro very similar to open-angle glaucoma occurring in humans. This model would impact in different fields such as ophthalmology, allowing long period of study of this pathology; pharmacology, evaluating the neuroprotective activity of active compounds; and pharmaceutical technology, allowing the correct evaluation of the efficacy of long-term sustained ocular drug delivery systems.

Formulation Optimization and In Vitro Characterization of Granisetronloaded Polylactic-co-glycolic Acid Microspheres Prepared by a Dropping-in-liquid Emulsification Technique.

Traditional dosage forms of granisetron (GRN) decrease patient compliance associated with repeated drug administration because of the short half-life of the drug. In this study, novel GRN-loaded Polylactic-co-glycolic Acid (PLGA) sustained-release microspheres were prepared for the first time via a dropping-in-liquid emulsification technique. The effects of various factors, such as pH of the outer phase, Tween 80, Polyvinyl Alcohol (PVA) concentrations, and hardening process, on the Encapsulation Efficiency (EE), Drug Loading (DL), and particle size of microspheres were extensively studied. The physicochemical properties, including drug release, surface morphology, crystallinity, thermal changes, and molecular interactions, were also studied. GRN has a pH-dependent solubility and it exhibits a remarkably high solubility under acidic condition. The EE of the alkaline medium (pH 8) was higher than that of the acidic medium (pH 4.0). EE and DL decreased in the presence of Tween 80 in the outer phase, whereas EE significantly increased during hardening. The particle size of microspheres was not affected by PVA and Tween 80 concentrations, but it was influenced by PVA volume and hardening. X-ray diffraction and differential scanning calorimetry results showed that the physical state of the drug changed from a crystalline form to an amorphous form, thereby confirming that the drug was encapsulated into the PLGA matrix. Fourier transform-infrared spectroscopy confirmed that some molecular interactions occurred between the drug and the polymer. GRN-loaded PLGA microspheres showed sustained release profiles of over 90% on week 3. GRN-loaded PLGA microspheres with sustained-release were successfully prepared, and they exhibited a relatively high EE without Tween 80 as an emulsifier and with the hardening process.

Regulation of mesenchymal stem cell osteogenic potential via microfluidic manipulation of microcarrier surface curvature

Microsphere-carriers have gained great interests as three-dimensional substrates for cultivation/expansion of tissue cells, required by cell-based therapy. However, how the microsphere curvature affects the cell proliferation/differentiation as well as the underlying signaling pathway of stem cells, and how to consequently regulate those cellular functionalities via manipulating microcarrier surface curvature, still remain to be explored. The current study was thus designed to develop a microfluidic manipulation technology to precisely control poly (lactic-co-glycolic) acid (PLGA) microsphere surface curvature, and subsequently to investigate the cellular responses and responding pathways of rat bone mesenchymal stem cells (BMSCs) cultured on these microspheres of predetermined curvature. A microfluidic device was developed to produce mono-distributed PLGA microspheres of diameters ranging from 52 µm to 250 µm, corresponding to curvatures (κ) from 1/26 µm−1 to 1/125 µm−1. BMSCs attachment and proliferation was evaluated on them and the one of κ = 1/82.5 µm−1 was shown to provide the most suitable microenvironment for cells to grow and undergo osteogenic differentiation. It was even found that F-actin cytoskeletal organization, nuclear distortion and expression of Lamin A were significantly enhanced by cells on the microcarriers of κ = 1/82.5 µm−1. Furthermore, a long non-coding RNA named lnc-LMNA, was found in this study to be the key factor associated with Lamin A to regulate osteogenic differentiation of BMSCs on spherical substrates. The current study thus provides a smart manipulation technology via microfluidic-manufacturing microcarriers to regulate cell functionalities, thereby enhancing desired therapeutic outcomes of cell-based regeneration or repair.

A hollow chitosan-coated PLGA microsphere to enhance drug delivery and anticancer efficiency

The use of poly lactic-co-glycolic acid (PLGA) microspheres is limited due to the low drug loading capacity and the shortage of surface functional groups. In order to overcome the shortcomings of pure PLGA carriers, chitosan (CS) is usually used to modify PLGA. To prepare a hollow chitosan (CS)-coated PLGA microsphere (MS) of paclitaxel (PTX) and to improve the drug-loading efficiency and anticancer efficiency as well as to reduce drug administration frequency, in this work, hollow PLGA microspheres with rough chitosan shell were prepared by the modified double-emulsion solvent evaporation method. Morphology analysis confirmed the successful preparation of the CS-PLGA-PTX with a rough surface and hollow internal structures. Due to the chitosan coating on PLGA microspheres, the particle size increased from 65.14 ± 14.36 μm to 73.46 ± 12.12 μm; the zeta potential increased from −17.96 ± 2.66 mV to 19.18 ± 1.64 mV. Drug loading efficiency increased from 7.36 ± 1.10% to 11.80 ± 0.22%, indicating that the hollow structure could provide enough hydrophobic space for PTX-loading. After being modified with chitosan, the initial burst release of PTX from microspheres decreased from 27.36 ± 3.03% to 18.68 ± 2.19% at pH = 7.4, only 9.91 ± 1.80% at pH = 5.5. Besides, the drug release behavior manifested that the rough chitosan shell could offer deep surface folds for fast degradation. The in vitro studies pointed to the prolongated anticancer activity of CS-PLGA-PTX; furthermore, the novel microspheres could induce the pro-apoptosis gene and protein expressions while lowering the drug resistance, causing extensive cancer cell apoptosis. In conclusion, the novel chitosan-coated PLGA microspheres with outstanding anticancer performance could serve as a promising treatment for liver cancer.

Fabrication of Radio-Opaque and Macroporous Injectable Calcium Phosphate Cement.

The aim of this work was the development of injectable radio-opaque and macroporous calcium phosphate cement (CPC) to be used as a bone substitute for the treatment of pathologic vertebral fractures. A CPC was first rendered radio-opaque by the incorporation of zirconium dioxide (ZrO2). In order to create macroporosity, poly lactic-co-glycolic acid (PLGA) microspheres around 100 μm were homogeneously incorporated into the CPC as observed by scanning electron microscopy. Physicochemical analyses by X-ray diffraction and Fourier transform infrared spectroscopy confirmed the brushite phase of the cement. The mechanical properties of the CPC/PLGA cement containing 30% PLGA (wt/wt) were characterized by a compressive strength of 2 MPa and a Young's modulus of 1 GPa. The CPC/PLGA exhibited initial and final setting times of 7 and 12 min, respectively. Although the incorporation of PLGA microspheres increased the force necessary to inject the cement and decreased the percentage of injected mass as a function of time, the CPC/PLGA appeared fully injectable at 4 min. Moreover, in comparison with CPC, CPC/PLGA showed a full degradation in 6 weeks (with 100% mass loss), and this was associated with an acidification of the medium containing the CPC/PLGA sample (pH of 3.5 after 6 weeks). A cell viability test validated CPC/PLGA biocompatibility, and in vivo analyses using a bone defect assay in the caudal vertebrae of Wistar rats showed the good opacity of the CPC through the tail and a significant increased degradation of the CPC/PLGA cement a month after implantation. In conclusion, this injectable CPC scaffold appears to be an interesting material for bone substitution.

Fat Graft with Allograft Adipose Matrix and Magnesium Hydroxide-Incorporated PLGA Microspheres for Effective Soft Tissue Reconstruction.

Autologous fat grafting is one of the most common procedures used in plastic surgery to correct soft tissue deficiency or depression deformity. However, its clinical outcomes are often suboptimal, and lack of metabolic and architectural support at recipient sites affect fat survival leading to complications such as cyst formation, calcification. Extracellular matrix-based scaffolds, such as allograft adipose matrix (AAM) and poly(lactic-co-glycolic) acid (PLGA), have shown exceptional clinical promise as regenerative scaffolds. Magnesium hydroxide (MH), an alkaline ceramic, has attracted attention as a potential additive to improve biocompatibility. We attempted to combine fat graft with regenerative scaffolds and analyzed the changes and viability of injected fat graft in relation to the effects of injectable natural, and synthetic (PLGA/MH microsphere) biomaterials. In vitro cell cytotoxicity, angiogenesis of the scaffolds, and wound healing were evaluated using human dermal fibroblast cells. Subcutaneous soft-tissue integration of harvested fat tissue was investigated in vivo in nude mouse with random fat transfer protocol Fat integrity and angiogenesis were identified by qRT-PCR and immunohistochemistry. In vitro cell cytotoxicity was not observed both in AAM and PLGA/MH with human dermal fibroblast. PLGA/MH and AAM showed excellent wound healing effect. In vivo, the AAM and PLGA/MH retained volume compared to that in the only fat group. And the PLGA/MH showed the highest angiogenesis and anti-inflammation. In this study, a comparison of the volume retention effect and angiogenic ability between autologous fat grafting, injectable natural, and synthetic biomaterials will provide a reasonable basis for fat grafting.

Sustained release of naringin from silk-fibroin-nanohydroxyapatite scaffold for the enhancement of bone regeneration.

Bone defects are a common challenge in the clinical setting. Bone tissue engineering (BTE) is an effective treatment for the clinical problem of large bone defects. In this study, we fabricated silk fibroin (SF)/hydroxyapatite (HAp) scaffolds inlaid with naringin poly lactic-co-glycolic acid (PLGA) microspheres, investigating the feasibility of their application in BTE. Naringin PLGA microspheres were manufactured and adhered to the SF/HAp scaffold. Bone mesenchymal stem cells (BMSCs) were inoculated onto the SF/HAp scaffold containing naringin PLGA microsphere to examine the biocompatibility of the SF/HAp scaffolds. A rabbit femoral distal bone defect model was used to evaluate the in vivo function of the SF/HAp scaffolds containing naringin-loaded PLGA microspheres. The current study demonstrated that SF/HAp scaffolds containing naringin-loaded PLGA microspheres show promise as osteo-modulatory biomaterials for bone regeneration.

The Bone Regeneration Capacity of BMP-2 + MMP-10 Loaded Scaffolds Depends on the Tissue Status.

Biomaterials-mediated bone formation in osteoporosis (OP) is challenging as it requires tissue growth promotion and adequate mineralization. Based on our previous findings, the development of scaffolds combining bone morphogenetic protein 2 (BMP-2) and matrix metalloproteinase 10 (MMP-10) shows promise for OP management. To test our hypothesis, scaffolds containing BMP-2 + MMP-10 at variable ratios or BMP-2 + Alendronate (ALD) were prepared. Systems were characterized and tested in vitro on healthy and OP mesenchymal stem cells and in vivo bone formation was studied on healthy and OP animals. Therapeutic molecules were efficiently encapsulated into PLGA microspheres and embedded into chitosan foams. The use of PLGA (poly(lactic-co-glycolic acid)) microspheres as therapeutic molecule reservoirs allowed them to achieve an in vitro and in vivo controlled release. A beneficial effect on the alkaline phosphatase activity of non-OP cells was observed for both combinations when compared with BMP-2 alone. This effect was not detected on OP cells where all treatments promoted a similar increase in ALP activity compared with control. The in vivo results indicated a positive effect of the BMP-2 + MMP-10 combination at both of the doses tested on tissue repair for OP mice while it had the opposite effect on non-OP animals. This fact can be explained by the scaffold’s slow-release rate and degradation that could be beneficial for delayed bone regeneration conditions but had the reverse effect on healthy animals. Therefore, the development of adequate scaffolds for bone regeneration requires consideration of the tissue catabolic/anabolic balance to obtain biomaterials with degradation/release behaviors suited for the existing tissue status.

Investigating dual drug loaded PLGA nanocarriers for improved efficacy in endometritis therapeutics

Modern endometritis therapeutics may require an extremely precise and controlled drug release system. Poly lactic-co-glycolic acid (PLGA) microspheres loaded with two different drugs like amoxicillin and vancomycin were prepared and their efficacy in management of endometritis in murine model was examined. Such biological nanocarriers are need of the hour since they are biodegradable, cytocompatible, hemocompatible and easily formulated. The sizes of the drug loaded PLGA microspheres ranged from 65–100 nm. The electron microscopy images depicted them as uniform spherical structures. The zeta potential and polydispersity index were calculated and the in vitro release investigation indicated steady drug release over a period of 50 h at effective dosage. The drug loaded nanocarriers were found with be cytocompatible and hemolysis test elaborated that they met with hemolysis rate safety requirements. The murine models were induced with endometritis by intravaginal administration of bovine uterine isolates. The mice were sacrificed and histopathogical examination of the endometrial slides stained with haematoxylin and eosin revealed that the drug loaded PLGA nanospheres helped in reducing acute endometritis in mice in a very short time. This study thereby demonstrated well described synthesis approach of drug loaded PLGA nanospheres which may be further be transferred to preclinical laboratory studies.

Combined local delivery of tacrolimus and stem cells in hydrogel for enhancing peripheral nerve regeneration.

The application of scaffold-based stem cell transplantation to enhance peripheral nerve regeneration has great potential. Recently, the neuroregenerative potential of tacrolimus (a U.S. Food and Drug Administration-approved immunosuppressant) has been explored. In this study, a fibrin gel-based drug delivery system for sustained and localized tacrolimus release was combined with rat adipose-derived mesenchymal stem cells (MSC) to investigate cell viability in vitro. Tacrolimus was encapsulated in poly(lactic-co-glycolic) acid (PLGA) microspheres and suspended in fibrin hydrogel, using concentrations of 0.01and 100 ng/ml. Drug release over time was measured. MSCs were cultured in drug-released media collected at various days to mimic systemic exposure. MSCs were combined with (i) hydrogel only, (ii) empty PLGA microspheres in the hydrogel, (iii) 0.01, and (iv) 100 ng/ml of tacrolimus PLGA microspheres in the hydrogel. Stem cell presence and viability were evaluated. A sustained release of 100 ng/ml tacrolimus microspheres was observed for up to 35 days. Stem cell presence was confirmed and cell viability was observed up to 7 days, with no significant differences between groups. This study suggests that combined delivery of 100 ng/ml tacrolimus and MSCs in fibrin hydrogel does not result in cytotoxic effects and could be used to enhance peripheral nerve regeneration.