Poly DL-lactide Research Articles

Synthesis of N-acetylcysteine functionalized cholic acid based triarmed poly DL-Lactide and encapsulation of gold nanoparticles: Studies on the antimicrobial activity and biocompatibility for drug delivery applications

Cholic acid based biodegradable reverse polymeric micelles have been widely utilized as preclinically suitable drug delivery system for poorly water-soluble drugs. In this report, we developed N-acetylcysteine functionalized cholic acid based triarmed poly (Dl-lactide) (ACyCA-triarmed (DLL)n as reversed polymeric micelles for drug delivery studies. ACyCA was synthesized via thiol-yne click reaction and subsequently used as an initiator for the synthesis of ACyCA-triarmed (DLL)n through ring opening polymerization (ROP) using Sn (Oct)2 as a catalyst. The synthesized ACyCA-triarmed (DLL)n was characterized using GPC, FT-IR, 1H NMR, 13C NMR, spectrofluorometer, HR-TEM, DSC, TGA, XRD, DLS, and zeta potential techniques. The reverse critical micellar concentration of the polymer was determined to be 1.99 mg/mL using a spectrofluorometer. The synthesized reverse micelles (RMs) were utilized as a reducing and capping agent for the preparation of AuNPs under sunlight exposure. The formed AuNPs exhibited spherical in shape with an average size of ∼ 23.4 nm and Dh was found to be 86.8 ± 1.3 nm as evidenced by the TEM and DLS analysis. Furthermore, the antimicrobial activity, hemolytic activity, anti-oxidant activity, and in-vitro drug release studies were examined for the RMs-AuNPs and compared with RMs. The hydrophobic nature of RMs and RMs-AuNPs had better haemocompatibility at above the reversed CMC. The antioxidant activity RMs-AuNPs showed better inhibitory effect in a dose-dependent manner as compared to RMs. The RMs-AuNPs formulation act as reservoir for solubilization of hydrophobic doxorubicin (Dox.HCl) drugs and can be used as therapeutic platform for slow and sustained release of drugs in biological medium.

Airbrushed nanofibers with bioactive core and antibacterial shell for wound healing application

Acute and chronic wounds are vulnerable to infection and delayed healing and require critical care and advanced wound protection. To overcome the challenges, dual therapy of antibacterial and growth factors will be a novel wound care strategy. The present study explores airbrushed core–shell nanofiber for dual delivery of epidermal growth factor (EGF) and amoxicillin (AMOX) in a sustained manner. A blend of polycaprolactone (PCL)-polyethylene oxide (PEO) was used to prepare the shell compartment for amoxicillin loading and poly-DL-lactide (PDLLA) core for EGF loading by using a customized airbrush setup. Characterization result shows a uniform distribution of nanofibers ranging between 200 and 500 nm in diameter. Amoxicillin loading in the shell compartment offers an initial burst release followed by a sustained release for up to 14 days. Whereas EGF in the core part shows a continuous sustained release throughout the release study.In-vitrostudy indicates the biocompatibility of EGF-AMOX loaded core–shell nanofibers with human dermal fibroblast cell (HDF) cells and a higher cellular proliferation compared to control samples. Gene expression data show an increase in fold change of collagen I and tropoelastin expression, indicating the regenerative properties of EGF-AMOX encapsulated nanofiber. The combination of bioactive core (EGF) and antibiotic shell (amoxicillin) in an airbrushed nanofibrous scaffold is a novel approach, which is the first time explored to deliver sustainable therapy to treat skin wounds. Our results demonstrate that PCL-PEO-Amoxicillin/PDLLA-EGF-loaded core–shell nanofibers are promising dual therapy scaffolds to deliver effective skin wound care, with the possibility of direct deposition on the wound.

Fentanyl-induced respiratory depression in rodents is inhibited by bioabsorbable, subcutaneous naltrexone implants at 3.5 months.

The aim of this study is to determine if extended-release, bioabsorbable, subcutaneous naltrexone (NTX) implants inhibit respiratory depression after an IV injection of fentanyl. Bioabsorbable implants fabricated from two different release-controlling polymers, poly-D-L-lactide (PDLLA) and polycaprolactone (PCL), alone (placebo) or containing NTX, were subcutaneously implanted in Sprague Dawley rats. After 3.5 months of implantation, the rodents were administered an IV bolus of fentanyl through the tail vein. The placebo implant rats received a dose of 4 micrograms (mcg) - (10 mcg/kg/dose), while the NTX implanted animals received a dose of 8 mcg (20 mcg/kg/dose). The minimum active dose of fentanyl that caused a > 50 ± 2% depression in the respiration rate in the placebo implanted rodents was 4 mcg. The respiration rate of the placebo implanted rats dropped from 208 ± 14 breaths/minute at predose, to 84 ± 12 breaths/minute (p = 0.0003) at 2 min. In contrast, all NTX implanted animals easily tolerated twice the dose of 8 mcg of fentanyl without any significant reduction in respiration rate. The mean respiration rate = increased from 164 ± 22 breaths/minute at predose to 178 ± 17 breaths/minute (p = 0.24) at 2 min. The mean plasma concentrations of NTX, 3.5 months after implantation, ranged from 7.4 (±1.1) ng/mL to 80.3 (±37.5) ng/mL. Bioabsorbable implants containing NTX effectively blocked fentanyl-induced respiratory depression in rodents as compared with placebo implants, 3.5 months after implantation.

In Vitro Coculture of Primary Human Cells to Analyze Angiogenesis, Osteogenesis, and the Inflammatory Response to Newly Developed Osteosynthesis Material for Pediatric Maxillofacial Traumatology: A Potential Pretesting Model before In Vivo Experiments

During the present study, an in vitro coculture bone tissue mimic based on primary osteoblasts and primary endothelial cells was used for a complex and broad evaluation of a newly developed material for applications in pediatric maxillofacial traumatology. The biomaterial was composed of PDLLA (poly(D,L-lactide)) in various combinations with calcium carbonate (CC), magnesium (Mg), and chitosan (CH). Besides classical biocompatibility analyses, the present study evaluated material-dependent effects on fundamental processes that are essential for successful material integration and regeneration. Therefore, inflammation-associated factors such as E-selectin and interleukins were analyzed in the in vitro model system on gene expression and protein level depending on the different materials. Furthermore, in order to test the capability of vascularization of the material, the effect of the different materials on the formation of microvessel-like structures as well as the expression and release of proangiogenic factors was investigated in vitro in the bone coculture model. In addition, the mineralization capacity as well as the relative gene expression of osteogenic differentiation factors was analyzed in response to the different materials. As a result, the authors could assess the material combination PDLLA: CC CH as the most functionally tested material with regard to biocompatibility, inflammatory response, and microvessel-like structure formation as well as osteogenic differentiation in the in vitro coculture system. In conclusion, by using tissue-engineered human bone tissue equivalents as proposed here in an in vitro coculture model, biomaterial-mediated effects can be readily investigated. Moreover, it is proposed that these complex in vitro evaluations could contribute to the understanding and improvement of the development of novel materials for pediatric traumatological care for prospective clinical applications.

High Adherence of Oral Streptococcus to Polylactic Acid Might Explain Implant Infections Associated with PLA Mesh Implantation.

The aim of this study was to evaluate and compare the biofilm formation properties of common pathogens associated with implant-related infections on two different implant material types. Bacterial strains tested in this study were Staphylococcus aureus, Streptococcus mutans, Enterococcus faecalis, and Escherichia coli. Implant materials tested and compared were PLA Resorb × polymer of Poly DL-lactide (PDLLA) comprising 50% poly-L-lactic acid and 50% poly-D-lactic acid) and Ti grade 2 (tooled with a Planmeca CAD-CAM milling device). Biofilm assays were done with and without saliva treatment to evaluate the effect of saliva on bacterial adhesion and to mimic the intraoral and extraoral surgical routes of implant placement, respectively. Five specimens of each implant type were tested for each bacterial strain. Autoclaved material specimens were first treated with 1:1 saliva-PBS solution for 30 min, followed by washing of specimens and the addition of bacterial suspension. Specimens with bacterial suspension were incubated for 24 h at 37 °C for biofilm formation. After 24 h, non-adhered bacteria were removed, and specimens were washed, followed by removal and calculation of adhered bacterial biofilm. S. aureus and E. faecalis showed more attachment to Ti grade 2, whereas S. mutans showed higher adherence to PLA in a statistically significant manner. The salivary coating of specimens enhanced the bacterial attachment by all the bacterial strains tested. In conclusion, both implant materials showed significant levels of bacterial adhesion, but saliva treatment played a vital role in bacterial attachment, therefore, saliva contamination of the implant materials should be minimized and considered when placing implant materials inside the body.

Bioinspired drug-delivery system emulating the natural bone healing cascade for diabetic periodontal bone regeneration.

Diabetes mellitus (DM) aggravates periodontitis, resulting in accelerated periodontal bone resorption. Disordered glucose metabolism in DM causes reactive oxygen species (ROS) overproduction resulting in compromised bone healing, which makes diabetic periodontal bone regeneration a major challenge. Inspired by the natural bone healing cascade, a mesoporous silica nanoparticle (MSN)-incorporated PDLLA (poly(dl-lactide))-PEG-PDLLA (PPP) thermosensitive hydrogel with stepwise cargo release is designed to emulate the mesenchymal stem cell “recruitment-osteogenesis” cascade for diabetic periodontal bone regeneration. During therapy, SDF-1 quickly escapes from the hydrogel due to diffusion for early rat bone marrow stem cell (rBMSC) recruitment. Simultaneously, slow degradation of the hydrogel starts to gradually expose the MSNs for sustained release of metformin, which can scavenge the overproduced ROS under high glucose conditions to reverse the inhibited osteogenesis of rBMSCs by reactivating the AMPK/β-catenin pathway, resulting in regulation of the diabetic microenvironment and facilitation of osteogenesis. In vitro experiments indicate that the hydrogel markedly restores the inhibited migration and osteogenic capacities of rBMSCs under high glucose conditions. In vivo results suggest that it can effectively recruit rBMSCs to the periodontal defect and significantly promote periodontal bone regeneration under type 2 DM. In conclusion, our work provides a novel therapeutic strategy of a bioinspired drug-delivery system emulating the natural bone healing cascade for diabetic periodontal bone regeneration.

Evaluation of the degradation of two bioabsorbable interference screws: an in-vivo study in sheep.

ABSTRACTPurpose:To evaluate in-vivo degradation of two bioabsorbable interference screws.Methods:Twenty-two crossbred Santa Inês ewes were used. A poly-DL-lactide (PDLLA) screw (70%/30%) was inserted in the right pelvic limb, and a PDLLA screw (70%) + β-tri-calcium phosphate (β-TCP) (30%) in the left pelvic limb. Animals were euthanized at one, four, seven and a half and 18 months after surgery. Plain radiography, computed tomography (CT), microCT, and histological analysis were accomplished.Results:PDLLA screw was hypodense at all evaluation moments, but with progressive density increase along the central axis, whereas PDLLA/β-TCP was initially hyperdense and progressively lost this characteristic. No adverse reactions were observed on histological evaluation.Conclusions:The inclusion of β-TCP favors screw degradation since the PDLLA/β-TCP screws evidenced a more intense degradation process than the PDLLA screws at the last evaluation. PDLLA screws showed higher bone production, evident around the screw thread, inside the lateral perforations, and in the central canal, whereas the PDLLA/β-TCP screws presented less bone tissue at the implantation site.

Poly (d/l) lactide-polycaprolactone/bioactive glass nanocomposites: assessments of in vitro bioactivity and biodegradability

The in vitro assessments suggested the essential features for the bio screws applications. The effects of bioactive glass nanoparticles (BG) during in vitro studies of the poly (D/L) lactide (PDLLA)/polycaprolactone (PCL)/BG nanocomposites (PPB) were assessed. The PDLLA/PCL (PP) blends were chosen as control groups. Apatite formations capabilities, weight and pH variations, alkaline phosphatase activity (ALP), and MTT assay were assigned during different immersion times up to 6 months. The XRD and SEM results revealed the superior apatite formation of PPB in simulated body fluids (SBF) compared to PP. The weight loss and pH variation results illustrated the highest values related to PP. Moreover, the MG-63 cells cultures determined the better cell viability of the PPB compared to the PP blends. Although, there are no statistically significant differences between the two groups. In addition, similar trends are shown for the ALP results where these amounts after 2 and 3 weeks incubation are considerable for PPB in comparison to PP. However, there are also no statistically significant differences between the two groups. Overall, the in vitro bioactivity and biodegradability confirmed that the PPB implants can be promised as a proper candidate for anterior cruciate ligament reconstruction screws.

In Vivo Assessments of the Poly(d/l)lactide/Polycaprolactone/Bioactive Glass Nanocomposites for Bioscrews Application

In the present study, in vivo properties of poly (D/L) lactide (PDLLA)/polycaprolactone (PCL)/bioactive glass nanocomposites (PPB) and PDLLA/PCL blends (PP) were investigated up to six months. The in vivo results from the implants inserted on canine models indicated that the weight losses of PPB and PP were approximately 60 and 70%, respectively. In addition, the average molecular weight of both specimens decreased as a function of grafting times; however, such decrease in trend of blends was more considerable than that in nanocomposites. Moreover, the obtained histological images of the animal model up to six months of implantation distinguished the formation of the new bone within the implanted area, while no osteitis and osteomyelitis or structural abnormality were observed. Overall, the animal in vivo tests results of implants within a period of 180 days confirmed the good biocompatibility among them and appropriate degradation behavior of PPB, hence a proper candidate for Anterior Cruciate Ligament Reconstruction (ACLR) screws.

Research Highlights

Research Highlights

Osteogenic differentiation of adipose-derived mesenchymal stem cells using 3D-Printed PDLLA/ β-TCP nanocomposite scaffolds

Designing bone scaffolds containing both organic and inorganic composites simulating the architecture of the bone is the most important principle in bone tissue engineering. The objective of this study was to fabricate a composite scaffold containing poly (D, l)-lactide (PDLLA) and β-tricalcium phosphate (β-TCP) as a platform for osteogenic differentiation of adipose-derived mesenchymal stem cells. In this study, PDLLA/β-TCP scaffolds were fabricated using three-dimensional printing (3D) technology through melt excursion technique. The physicomechanical characteristics, including microstructure, mechanical properties, of the customized scaffolds were investigated. Further, the in vitro biological characteristics of manufactured scaffolds were evaluated in conjugation with buccal fat pad derived mesenchymal stem cells in terms of cell attachment, viability, proliferation, and osteogenic differentiation capacity. The 3D printed customized scaffold in this study showed proper pore size, porosity, mechanical strength, material composition, biocompatibility, and osteogenic differentiation capacity. The obtained results converge to reveal the promising features of the nanocomposite 3D printed platform for personalized bone tissue engineering.

In Vitro Study of Degradation Behavior, Cytotoxicity, and Cell Adhesion of the Atactic Polylactic Acid for Biomedical Purposes

An atactic poly-d,l-lactide (PLA) is obtained via ring-opening polymerization (ROP) of lactide stereoisomers mixture catalyzed by the magnesium and calcium acenaphthylenebisamido complexes. The polymer is characterized by gel-permeation chromatography, NMR spectroscopy, and mass spectrometry. The hydrolytic degradation behavior, cytotoxicity, and cell adhesion of the resulting PLA are evaluated. The polymer degrades in phosphate-buffered saline, releasing water-soluble low molecular products that significantly influence dermal fibroblast growth. Polymer demonstrates no cytotoxicity that, along with cell adhesion and their high proliferative activity toward the PLA obtained, proves its biocompatibility.

The synergetic effect of bioactive molecule-loaded electrospun core-shell fibres for reconstruction of critical-sized calvarial bone defect-The effect of synergetic release on bone Formation.

ObjectivesBone regeneration is a complex process modulated by multiple growth factors and hormones during long regeneration period; thus, designing biomaterials with the capacity to deliver multiple bioactive molecules and obtain sustained release has gained an increasing popularity in recent years. This study is aimed to evaluate the effect of a novel core‐shell electrospun fibre loaded with dexamethasone (DEX) and bone morphogenetic protein‐2 (BMP‐2) on bone regeneration.Materials and methodsThe core‐shell electrospun fibres were fabricated by coaxial electrospinning technology, which were composed of poly‐D, L‐lactide (PLA) shell and poly (ethylene glycol) (PEG) core embedded with BMP‐2 and DEX‐loaded micelles. Morphology, hydrophilicity, gradation, release profile of BMP‐2 and DEX, and cytological behaviour on bone marrow mesenchymal stem cells (BMSCs) were characterized. Furthermore, the effect on bone regeneration was evaluated via critical‐sized calvarial defect model.ResultsThe electrospun fibres were featured by the core‐shell fibrous architecture and a suitable degradation rate. The sustained release of DEX and BMP‐2 was up to 562 hours. The osteogenic gene expression and calcium deposition of BMSCs were significantly enhanced, indicating the osteoinduction capacity of electrospun fibres. This core‐shell fibre could accelerate repair of calvarial defects in vivo via synergistic effect.ConclusionsThis core‐shell electrospun fibre loaded with DEX and BMP‐2 can act synergistically to enhance bone regeneration, which stands as a strong potential candidate for repairing bone defects.

Hybrid Lipid Polymer Nanoparticles for Combined Chemo- and Photodynamic Therapy.

Retinoblastoma is a malignant tumor of the retina in infants. Conventional therapies are associated to severe side effects and some of them induce secondary tumors. Photodynamic therapy (PDT) thus appears as a promising alternative as it is nonmutagenic and generates minimal side effects. The effectiveness of PDT requires the accumulation of a photosensitizer (PS) in the tumor. However, most porphyrins are hydrophobic and aggregate in aqueous medium. Their incorporation into a nanocarrier may improve their delivery to the cell cytoplasm. In this work, we designed biodegradable liponanoparticles (LNPs) consisting of a poly(d,l)-lactide (PDLLA) nanoparticle coated with a phospholipid (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/1,2-dioleoyl-3-trimethylammonium-propane) bilayer. An anticancer drug, beta-lapachone (β-Lap) and a PS, m-THPC, were co-encapsulated for combined chemo- and PDT because it has been suggested that they may have a synergistic effect based on the activation of β-Lap by PDT-induced over-expression of the enzyme NQO1. Using dynamic light scattering measurements, cryogenic transmission electron microscopy, and fluorescence confocal microscopy, we selected the appropriate conditions for the encapsulation of the compounds. LNPs were internalized in retinoblastoma cells within few hours. No obvious synergistic effect related to the activation of β-Lap by PDT was observed. Conversely, the LNPs were cytotoxic at lower doses of the two encapsulated compounds as compared to the single therapies. Analysis of the combinatorial treatment showed that PDT and chemotherapy had an additive effect on the viability of retinoblastoma cells.

A novel controlled release tetrandrine-loaded PDLLA film: evaluation of drug release and anti-adhesion effects in vitro and in vivo

To investigate the drug release and anti-adhesion effects of a TET (tetrandrine)-loaded PDLLA (poly-dl-lactide) film. Detection of TET release in vitro was carried out by high-performance liquid chromatography (HPLC) every 2 days following immersion of the tetrandrine-loaded PDLLA film in simulated body fluid until the TET content of the eluate could not be detected. For the in vivo test, TET-loaded PDLLA films were implanted into animal laminectomy models and positive and blank control groups were also set up. Postoperative serum tests, and macroscopic and histological analyses at 1, 4, 8, and 12 weeks, were used to assess the effects of the film. Statistical analyses were performed by one-way ANOVA. The drug release of the tetrandrine-loaded PDLLA film in vitro showed two phases with a second release peak. Ultimately, the duration of continuous delivery was up to 66 days and the cumulative delivery rate was up to 93.18%. Scores for the proliferation of epidural scars or adhesion of the dura mater in the test group were much lower than those for the two control groups. Histological analysis revealed the test group had fewer inflammatory cells and fibroblasts, as well as fewer extracellular collagen fibers, and a lower histology score than those of the two control groups at all time points. Tetrandrine-loaded PDLLA film is a novel controlled drug release and anti-adhesion material in vitro and in vivo.

Sugar Concentration and Arrangement on the Surface of Glycopolymer Micelles Affect the Interaction with Cancer Cells.

Glycopolymer-coated nanoparticles have attracted significant interest over the past few years, because of their selective interaction with carbohydrate receptors found on the surface of cells. While the type of carbohydrate determines the strength of the ligand-receptor interaction, the presentation of the sugar can be highly influential as the carbohydrate needs to be accessible in order to display good binding. To shine more light on the relationship between nanoparticle structure and cell uptake, we have designed several micelles based on fructose containing block copolymers, which are selective to GLUT5 receptors found on breast cancer cell lines. The polymers were based on poly-d,l-lactide (PLA), poly(2-hydroxyethyl) acrylate (PHEA), and poly(1- O-acryloyl-β-d-fructopyranose) (P[1- O-AFru]). A set of six micelles was synthesized based on four fructose containing micelles (PLA242- b-P[1- O-AFru]41, PLA242- b-P[1- O-AFru]179, PLA242- b-P[1- O-AFru46-c-HEA214], PLA242- b-PHEA280- b-P[1- O-AFru]41) and two neutral controls (PLA247- b-PHEA53 and PLA247- b-PHEA166). SAXS analysis revealed that longer hydrophilic polymers led to lower aggregation numbers and larger hydrophilic shells, suggesting more glycopolymer mobility. Cellular uptake studies via flow cytometry and confocal laser scanning microscopy (CLSM) confirmed that the micelles based on PLA242- b-P[1- O-AFru]179 show, by far, the highest uptake by MCF-7 and MDA-MB-231 breast cancer cell lines while the uptake of all micelles by RAW264.7 cell is negligible. The same micelle displayed was far superior in penetrating MCF-7 cancer spheroids (three-dimensional (3D) model). Taking the physicochemical characterization obtained by SAXS and the in vitro results together, it could be concluded that the glycopolymer chains on the surface of micelle must display high mobility. Moreover, a high density of fructose was found to be necessary to achieve good biological activity as lowering the epitope density led immediately to lower cellular uptake. This work showed that it is crucial to understand the micelle structure in order to maximize the biological activity of glycopolymer micelles.

Feasibility of a Three-Dimensional Porous Uncalcined and Unsintered Hydroxyapatite/poly-d/l-lactide Composite as a Regenerative Biomaterial in Maxillofacial Surgery.

This study evaluated the feasibility of a novel three-dimensional (3D) porous composite of uncalcined and unsintered hydroxyapatite (u-HA) and poly-d/l-lactide (PDLLA) (3D-HA/PDLLA) for the bony regenerative biomaterial in maxillofacial surgery, focusing on cellular activities and osteoconductivity properties in vitro and in vivo. In the in vitro study, we assessed the proliferation and ingrowth of preosteoblastic cells (MC3T3-E1 cells) in 3D-HA/PDLLA biomaterials using 3D cell culture, and the results indicated enhanced bioactive proliferation. After osteogenic differentiation of those cells on 3D-HA/PDLLA, the osteogenesis marker genes runt-related transcription factor-2 (Runx2), and Sp7 (Osterix) were upregulated. For the in vivo study, we evaluated the utility of 3D-HA/PDLLA biomaterials compared to the conventional bone substitute of beta-tricalcium phosphate (β-TCP) in rats with critical mandibular bony defects. The implantation of 3D-HA/PDLLA biomaterials resulted in enhanced bone regeneration, by inducing high osteoconductivity as well as higher β-TCP levels. Our study thus showed that the novel composite, 3D-HA/PDLLA, is an excellent bioactive/bioresorbable biomaterial for use as a cellular scaffold, both in vitro and in vivo, and has utility in bone regenerative therapy, such as for patients with irregular maxillofacial bone defects.

Polymeric and Non Polymeric Injectable In-situ Forming Implant Systems for Sustained Delivery of Lornoxicam: In vitro and In vivo Evaluation.

Formulation of injectable In situ forming implant (ISI) systems of lornoxicam for dental and postoperative pain management to decrease dosing frequency and increase patient compliance. Polymeric in situ implant solutions were prepared using different concentrations and inherent viscosities of Poly-DL-lactide (PDL) or DL-lactide/glycolide copolymer (PDLG) using 22X4 factorial experimental design. Nonpolymeric systems were prepared using different concentrations of lipids like cetyl alcohol and stearyl alcohol and also sucrose acetate isobutyrate (SAIB) using 32 factorial experimental design. In vitro release study, rheological measurement, syringeability assessment and effect of γ-sterilization were used for evaluation of the prepared formulae. In vivo pharmacokinetic study of lornoxicam from the most optimum formula was conducted in a rabbit model using HPLC analysis of blood samples. Polymeric systems showed high burst release followed by very slow release rate over 72 hours. Formula I 24 (containing SAIB 80% (w/w)) showed relatively low burst release followed by diffusion controlled release pattern, low viscosity, Newtonian flow behavior and good syringeability. γ- sterilization had no significant effect on the in vitro release and the physical nature of the most optimum formula. In vivo study concluded that intramuscularly injected In situ implant formula I 24 showed prolonged release pattern compared to the marketed product which was indicated by the increased Tmax and the extended mean residence time. Lornoxicam ISI systems could be promising as convenient injectable sustained release delivery systems for dental and postoperative pain management.

Guided bone regeneration using a bone tissue engineering complex consisting of a poly-dl-lactide membrane and bone mesenchymal stem cells.

Developmental dysplasia of the hip (DDH) is one of the most common diseases encountered in pediatric orthopedic departments. Current treatment strategies seek to improve acetabular coverage, the principal defect of acetabular dysplasia, but are not very successful. We developed a guided bone regeneration (GBR) strategy to improve acetabular coverage via bone tissue engineering (BTE). Poly-dl-lactide (PDLLA) membranes were seeded with bone marrow mesenchymal stem cells (BMSCs) to form a BTE complex, which was then implanted into the superior margin of the acetabulum in a rabbit DDH model. Twelve weeks later, a small amount of high-density shadowing was evident on X-rays of the superior margin of the acetabulum, specimens of which exhibited new bone formation. Micro-computed tomography yielding three-dimensional images revealed that new bone had formed in the superior acetabulum, the basal part of which had fused with (and thus reconstructed) the autogenous bone, and new trabecular bone featuring transverse interlacing was evident in the interior of the hip. No clear evidence of bone formation was observed in rabbits that underwent sham operations or that were implanted with PDLLA only. Thus, it may be possible to improve acetabular coverage via BTE-based bone regeneration.

Synthesis, characterization and application of biodegradable polymer grafted novel bioprosthetic tissue

Animal tissue has an extended history of clinical use in applications like heart valve bioprosthesis devices, cardiovascular surgical applications etc. but often does not last long after implantation in the body due to rapid unwanted degradation. The goal of this work is to develop novel composite biomaterials by grafting biological tissue with synthetic, biodegradable polymers. In the current research phase, porcine submucosa, ureter and bovine pericardial tissue are grafted with poly DL-lactide (PLA), poly glycolide (PGA) and poly DL-lactide glycolide (PLGA) copolymers. The grafted and control tissues are characterized by FTIR and SEM. The biodegradability of the tissue-graft composite materials is determined by pepsin and collagenase digestion assays, showing it can be tailored by varying the grafted polymer type and amount. The grafted tissues can be tuned for a particular clinical or tissue engineering applications including drug delivery with little or no burst release and sustained/controlled delivery.