Evaluation of the osteoconductive potential of poly(propylene carbonate)/nano-hydroxyapatite composites mimicking the osteogenic niche for bone augmentation

Nano-hydroxyapatite (n-HA) reinforced poly(propylene carbonate) (PPC) composites were prepared for bone repair and reconstruction. The effects of reinforcement on the morphology, mechanical properties and biological performance of n-HA/PPC composites were investigated. The surface morphology and mechanical properties of the composites were characterized by scanning electron microscopy (SEM) and universal material testing machine. The analytical data showed that good incorporation and dispersion of n-HA crystals could be obtained in the PPC matrix at a 30:70 weight ratio. With the increase of n-HA content, the tensile strength increased and the fracture elongation rate decreased. In vitro cell culture revealed that the composite was favorable template for cell attachment and growth. In vivo implantation in femoral condyle defects of rabbits confirmed that the n-HA/PPC composite had good biocompatibility and gradual biodegradability, exhibiting good performance in guided bone regeneration. The results demonstrates that the incorporation of n-HA crystals into PPC matrix provides a practical way to produce biodegradable and cost-competitive composites mimicking the osteogenic niche for bone augmentation.     

n-Hydroxyapatite/PCL-Pluronic-PCL Nanocomposites for Tissue Engineering. Part 2: Thermal and Tensile Study

In this work a series of nano-hydroxyapatite/poly(ε-caprolactone)-Pluronic-poly(ε-caprolactone) (n-HA/PCFC) nanocomposites has been prepared. Thermal properties of the nanocomposites are studied by thermogravimetry analysis (TGA) and differential scanning calorimetry (DSC). The TGA/DTG results reveal that thermal stability of n-HA/PCFC nanocomposites is improved by incorporation of n-HA into polymer matrix, and the thermo-degradation temperature increased slightly with increasing HA loading. DSC results show that the glass transition temperature (T _g) changed by the addition of n-HA. The mechanical properties of the nanocomposites are investigated by tensile testing. The morphology for tensile-fractured surfaces of nanocomposites is observed by scanning electron microscopy. The effect of n-HA contents of nanocomposites on tensile strength and morphology is also discussed.     

Antibacterial nanohydroxyapatite/polyurethane composite scaffolds with silver phosphate particles for bone regeneration

Solving the issue of infection associated with implanted bone substitutes is one of the modern challenges of the biomedical engineering field. The purpose of this study was to develop a novel porous scaffold with sufficient antibacterial activity for bone repair or regeneration. Porous nanohydroxyapatite/polyurethane (n-HA/PU) composite scaffolds containing different amounts of silver phosphate particles were prepared through the in situ foaming method. Subsequently, their physicochemical properties, antibacterial abilities, and preliminary cytocompatibilities were evaluated. The results indicated that the porosity and mechanical properties of the n-HA/PU scaffolds incorporated with Ag₃PO₄ did not change significantly compared to n-HA/PU scaffold without Ag₃PO₄. The release of Ag⁺ was time and concentration dependent, increasing with the immersion time and Ag₃PO₄ percentage in the scaffolds. A continuous Ag⁺ release can last more than 3 weeks. The antibacterial tests and cytocompatibility evaluation revealed that n-HA/PU scaffolds with 3 wt% Ag₃PO₄ (n-HA/PU3) exhibit stronger antimicrobial effects as well as satisfactory cytocompatibility. The n-HA/PU3 scaffolds may hold great potential for application in the field of bone regeneration, especially for infection-associated bone defect repair.     

纳米微球负载抗生素/羟基磷灰石复合支架的缓释性能及治疗感染性骨缺损的研究

目的 评价新型纳米微球负载抗生素/羟基磷灰石复合支架材料的体外缓释性能及治疗感染性骨缺损的疗效。方法 运用HPLC法检测不同时间点药物的体外释放量。建立兔胫骨感染性骨缺损动物模型24只,共分为4组：a组动物仅单纯清创;b组植入1 mg Lev/PMMA;c组植入n-HA/PU;d组植入1 mg Lev/n-HA/PU。在植入材料术后6周、12周观察放射学、组织病理学,Micro CT评价新骨生成。评价新型复合材料控制感染、诱导成骨能力、治疗感染性骨缺损的效果。结果 1 mg Lev/n-HA/PU组比1 mg Lev/PMMA组释放的抗生素更多（P<0.05）,缓释性能表现更好。单纯清创组X线表现出局部骨破坏、死骨形成。1 mg Lev/n-HA/PU组无明显骨破坏。Micro CT发现1 mg Lev/n-HA/PU组材料周围新生骨小梁数量与其余三组比较,差异有统计学意义（P<0.05）,结论 新型载抗生素复合支架材料具有良好的缓释性能、抗感染能力、骨诱导能力,可有效治疗胫骨感染性骨缺损。     

Preparation and properties of nano-hydroxyapatite/PCL-PEG-PCL composite membranes for tissue engineering applications

Nano-hydroxyapatite (n-HA)/poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) composite membranes were prepared by solvent casting and evaporation method. The structure and properties of the membranes were investigated by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), water contact angle measurements, in vitro hydrolytic degradation, mechanical test, and cell culture. The effect of n-HA content on physical-chemical properties of the n-HA/PCEC composite membranes was studied. The results showed that the shape and size of micropores of the composite membranes changed with n-HA content increased; the tensile strength decreased with the increase of n-HA content. The osteoblast cell was cultured on the membranes, good cell attachment and growth manner were observed after postseeding for 1 day. MTT assays showed that the n-HA/PCEC membranes had no negative effect on the cell viability and proliferation. These results suggested that the obtained n-HA/PCEC composite membranes in this study might have prospective applications in tissue engineering field.     

Polyurethanes Containing an Imidazolium Diol‐Based Ionic‐Liquid Chain Extender for Incorporation of Ionic‐Liquid Electrolytes

Novel polyurethane (PU) cationomers are synthesized using an imidazolium diol‐based ionic liquid (IL) chain extender. A systematic comparison with a non‐ionic PU analogue reveals effect of the imidazolium cation on physical properties, hydrogen bonding, and morphology of segmented PU. Casting resulting PU solutions with various contents of IL generates novel membranes. Thermal study reveals that IL‐containing PU membranes exhibit a constant soft segment T_g at ?81 °C; however, the T_g of imidazolium hard segments systematically shifts to lower temperatures with increasing IL content. This suggests that IL preferentially locates into the imidazolium ionic hard domains, which is also evident in small‐angle X‐ray scattering. Moreover, dielectric relaxation spectroscopy demonstrates increased ionic conductivity of PU membranes by 5 orders of magnitude upon incorporation of 30 wt% IL.

     

Development of Biodegradable Polyurethane Scaffolds Using Amino Acid and Dipeptide-Based Chain Extenders for Soft Tissue Engineering

The inherent flexibility of polyurethane (PU) chemistry allows the incorporation of specific chemical moieties into the backbone structure conferring a unique biological function to these synthetic polymers. We describe here the synthesis and characterization of a PU containing a Gly–Leu linkage, the cleavage site of several matrix metalloproteinases. A Gly–Leu dipeptide was introduced into the chain extender of the polyurethane through the reaction with 1,4-cyclohexane dimethanol. PUs synthesized with the Gly–Leu-based chain extender had a high weight-average molecular weight (M _w > 125 × 10³) and were phase segregated, semi-crystalline polymers with a low soft-segment glass-transition temperature (T _g < –50°C). Uniaxial tensile testing of PU films indicated that the polymer could withstand high ultimate tensile strengths (approx. 13 MPa) and were flexible with breaking strains of approx. 900%. The Gly–Leu PU had a significantly higher initial modulus, yield stress and ultimate stress compared to a PU previously developed in our laboratory containing a phenylalanine-based chain extender (Phe PU). The Gly–Leu-based chain extender allowed for better hard segment packing and hydrogen bonding leading to enhanced mechanical properties. Electrospinning was used to form scaffolds with randomly organized fibers and an average fiber diameter of approx. 3.6 μm for both the Gly–Leu and Phe PUs. Mouse embryonic fibroblasts were successfully cultured on the PU scaffolds out to 28 days. Further investigations into cell-mediated polymer degradation will help to identify the suitability of this new biomaterial as scaffolds for soft tissue applications.     

纳米羟基磷灰石/脂肪族聚酯酰胺复合材料

在本实验中,水热合成的纳米羟基磷灰石(n-HA)作为无机相与新型的可降解的脂肪族聚酯酰胺(PEA)按不同比例复合.PEA及其复合材料的结构、性能通过透射电镜、红外光谱、X线衍射、扫描电镜及原子能谱等检测表征.结果表明,形貌尺寸相似于天然骨组织磷灰石结晶的纳米羟基磷灰石晶体均匀分散于PEA有机基质中,复合材料的两相间存在分子间作用力,提高了复合材料的力学性能.同时体外细胞学实验表明该材料具有良好的细胞相容性,显示了该复合生物材料在组织工程支架材料方面的应用前景.     

Attachment,proliferation and collagen type I mRNA expression of human gingival fibroblasts on different biodegradable membranes

Abstract

The purpose of this study was to investigate adhesion, proliferation and type I collagen (COL I) mRNA expression of gingival fibroblasts on different membranes used in periodontal applications. Collagen (C), acellular dermal matrix (ADM) and polylactic acid; polyglycolic acid; lactide/glycolide copolymer (PLGA) biodegradable membranes were combined with gingival fibroblasts in culture and incubated for 48?h. Cell adhesion was examined with scanning electron and confocal microscopy. MTT assay was used to measure proliferation. COL I mRNA expression was assessed using quantitative-polymerase chain reaction (QPCR). The PLGA group exhibited the lowest cell survival on day 5 and 10, and lowest cell proliferation on days 5, 10 and 14. While cell proliferation was similar in C and ADM groups, the C membrane showed a slightly greater increase in viable cells to day 10. Confocal and scanning electron microscopy confirmed the results of proliferation and MTT assays. The highest COL I mRNA expression was noted in the PLGA membrane group when compared to the C (p?<?0.01) and ADM (p?<?0.05) membrane groups. These data revealed that adherence and proliferation of primary gingival fibroblasts on collagen-based C and ADM membranes is better than that seen with PLGA membranes, and thus may be preferable in the treatment of gingival recession defects.     

The herpes simplex virus 1 U(S)3 regulates phospholipid synthesis

Herpes simplex virus type 1 capsids bud at nuclear and Golgi membranes for envelopment by phospholipid bilayers. In the absence of U_S3, nuclear membranes form multiple folds harboring virions that suggests disturbance in membrane turnover. Therefore, we investigated phospholipid metabolism in cells infected with the U_S3 deletion mutant R7041(ΔU_S3), and quantified membranes involved in viral envelopment. We report that (i) [³H]-choline incorporation into nuclear membranes and cytoplasmic membranes was enhanced peaking at 12 or 20 h post inoculation with wild type HSV-1 and R7041(ΔU_S3), respectively, (ii) the surface area of nuclear membranes increased until 24 h of R7041(ΔU_S3) infection forming folds that equaled ∼45% of the nuclear surface, (iii) the surface area of viral envelopes between nuclear membranes equaled ∼2400 R7041(ΔU_S3) virions per cell, and (iv) during R7041(ΔU_S3) infection, the Golgi complex expanded dramatically. The data indicate that U_S3 plays a significant role in regulation of membrane biosynthesis.     

Biodegradable elastomeric polyurethane membranes as chondrocyte carriers for cartilage repair

Autologous chondrocyte implantation in combination with an autologous periosteal patch has become a clinically accepted procedure for the treatment of articular cartilage defects. The use of periosteum has, however, several drawbacks. We have been able to fabricate thin elastomeric biodegradable polyurethane (PU) membranes that may possibly have an application as a tissue-engineered substitute for the periosteal patch. Three types of membranes varying in pore size and surface texture were used as substrates for bovine chondrocytes in culture. The membranes, marked as P-I, P-II, and P-R, had average pore sizes of 10 to 20 microm, 40 to 60 microm, and less than 5 microm, respectively. A poly(L/DL-lactide) 80/ 20% micro-porous membrane (PLA) with an average pore size in the range of 10 to 70 microm was used as a control. There was no difference in the cell proliferation profile among the 4 membranes. In terms of proteoglycan and collagen production, P-I, P-R, and PLA performed similarly to one another. The rate of matrix production appears to be greater in the PU membranes than in the PLA membrane in the first 10 days, although by day 30, the PLA membrane had caught up. In all comparisons, the performance of P-II lagged behind those of the other materials. In conclusion, this preliminary study supports the potential use of this novel group of PUs as a periosteal flap substitute or perhaps as a chondrocyte carrier for matrix-assisted chondrocyte implantation and related techniques. Further studies will be necessary to better define their role in clinical applications for cartilage repair.     

Physical properties and biocompatibility of cellulose/soy protein isolate membranes coagulated from acetic aqueous solution

A series of cellulose/soy protein isolate (SPI) membranes was prepared from cellulose and SPI solution by casting and coagulation from 5 wt% acetic acid and 5 wt% sulphuric acid aqueous solution, respectively. The structure and properties of the membranes were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy and tensile testing. The effects of SPI content (W _SPI) and the coagulants on the structure and properties of the membranes were investigated. The membranes exhibited porous structure. The pore size in the surfaces and cross-sections of the membranes increased with an increase of W _SPI regardless of the coagulants. The membranes containing 10 wt% W _SPI showed higher tensile strength and elongation at break than other membranes. The membranes with the same W _SPI coagulated from acetic acid solution exhibited higher values of tensile strength, elongation at break and pore size in the surfaces and cross-sections than those corresponding membranes coagulated from sulphuric acid. The biocompatibility of the acetic acid-coagulated membranes was preliminarily evaluated by cell culture and in vivo implantation experiments. The results revealed that human umbilical vein endothelial cells (ECV304) grew well on this biomaterial. In comparison with the pure cellulose membrane, because of the incorporation of SPI and the resultant alteration of microstructure, the SPI-modified membranes showed an improved in vivo biocompatibility and biodegradability in the implantation experiments. These cellulose/SPI membranes warrant further explorations in biomedical fields.     

Transport of proteins across mitochondrial membranes

The vast majority of proteins comprising the mitochondrion are encoded by nuclear genes, synthesized on ribosomes in the cytosol, and translocated into the various mitochondrial subcompartments. During this process proteins must cross the lipid membranes of the mitochondrion without interfering with the integrity or functions of the organelle. In recent years an approach combining biochemical, molecular, genetic, and morphological methodology has provided insights into various aspects of this complex process of intracellular protein sorting. In particular, a greater understanding of the molecular specificity and mechanism of targeting of mitochondrial preproteins has been reached, as a protein complex of the outer membrane which facilitates recognition and initial membrane insertion has been identified and characterized. Furthermore, pathways and components involved in the translocation of preproteins across the two mitochondrial membranes are being dissected and defined. The energetics of translocation and the processes of unfolding and folding of proteins during transmembrane transfer are closely linked to the function of a host of proteins known as heat-shock proteins or molecular chaperones, present both outside and inside the mitochondrion. In addition, the analysis of the process of folding of polypeptides in the mitochondrial matrix has allowed novel and unexpected insights into general pathways of protein folding assisted by folding factors. Pathways of sorting of proteins to the four different mitochondrial subcompartments — the outer membrane (OM), intermembrane space, inner membrane (IM) and matrix — are only partly understood and reveal an amazing complexity and variation. Many additional protein factors are involved in these latter processes, a few of which have been analyzed, such as cytochrome c heme lyase and cytochrome c ₁ heme lyase, enzymes that catalyze the covalent addition of the heme group to cytochrome c and c ₁ preproteins, and the mitochondrial processing peptidase which cleaves signal sequence after import of preproteins into the matrix. Thus, the study of transport of polypeptides through the mitochondrial membranes does not only contribute to the understanding of how biological membranes facilitate the penetration of macromolecules but also provides novel insights into the structure and function of this organelle. are being dissected and defined. The energetics of translocation and the processes of unfolding and folding of proteins during transmembrane transfer are closely linked to the function of a host of proteins known as heat-shock proteins or molecular chaperones, present both outside and inside the mitochondrion. In addition, the analysis of the process of folding of polypeptides in the mitochondrial matrix has allowed novel and unexpected insights into general pathways of protein folding assisted by folding factors. Pathways of sorting of proteins to the four different mitochondrial subcompartments — the outer membrane (OM), intermembrane space, inner membrane (IM) and matrix — are only partly understood and reveal an amazing complexity and variation. Many additional protein factors are involved in these latter processes, a few of which have been analyzed, such as cytochrome c heme lyase and cytochrome c ₁ heme lyase, enzymes that catalyze the covalent addition of the heme group to cytochrome c and c ₁ preproteins, and the mitochondrial processing peptidase which cleaves signal sequences after import of preproteins into the matrix. Thus, the study of transport of polypeptides through the mitochondrial membranes does not only contribute to the understanding of how biological membranes facilitate the penetration of macromolecules but also provides novel insights into the structure and function of this organelle.Abbreviations OM outer mitochondrial membrane - IM inner mitochondrial membrane - IMS mitochondrial intermembrane space - OMV outer membrane vesicles - AAC ADP/ATP carrier - PiC phosphate carrier - DHFR mouse cytosolic dihydrofolate reductase - F₁ subunit of F₁F₀ ^– ATPase - MPP mitochondrial processing peptidase     

Cell separation of hepatocytes and fibroblasts through surface-modified polyurethane membranes

The separation of fibroblast cells (L929 cells) and hepatocytes was investigated by using unmodified and surface-modified polyurethane (PU) foaming membranes (pore size of 12 microm) by the incorporation of various functional groups. L929 cells permeated more readily than hepatocytes, and very few populations of hepatocytes (<5%) permeated through the membranes. This result was thought to be due to the smaller cell size of the L929 cells (5-10 microm) relative to the hepatocytes (15-30 microm). The larger hepatocytes were thought to plug the pores of the membranes. A good cell separation between L929 cells and hepatocytes was achieved when the cell mixture permeated through the negatively charged PU membranes. The negatively charged membranes were thought to enhance the permeation of L929 cells because of the electrostatic repulsion between the membranes and negatively charged cells. On the other hand, the hepatocytes were unable to permeate through the membranes because of the sieve effect caused by their large cell size. The separation of hepatocytes isolated from mice at different ages was also accomplished by permeating the cell mixture through unmodified and surface-modified PU membranes.     

Heparin dopant increases the electrical stability, cell adhesion, and growth of conducting polypyrrole/poly(L,L-lactide) composites

Polypyrrole (PPy) is a promising conductive polymer for tissue engineering and bioelectrical applications. However, its electrical conductivity deteriorates easily in aqueous conditions. Cell adhesion to PPy is also relatively poor. The goal of this study was to simultaneously improve the electrical stability of and cell adhesion to PPy by using heparin (HE) as dopant, for HE is both a polyanion and an important glycosaminoglycan in cell membranes and extracellular matrix. PPy particles doped with HE were synthesized through emulsion polymerization using Fenton's reagent as an oxidant. X-ray photoelectron spectroscopy (XPS), infrared and scanning electron microscopy (SEM) were used to investigate the PPy particles. Conductive biodegradable membranes of 10(2) to 10(3) Omega/square were prepared from 5% (w) PPy with various amounts of HE and 95% (w) poly(L,L-lactide) (PPy/PLLA). Azure A staining was employed to quantify the HE exposed on the surface of the PPy particles and PPy/PLLA membranes. The distribution of HE on membranes was demonstrated by DAPI staining. Results showed that HE was incorporated into the PPy particles as counterions and presented on particle surface. A unique "filament"-like morphology of the PPy preparation was observed at high-HE content. The electrical stability of the PPy/PLLA membranes was tested in saline at 37 degrees C for 500 h. Human skin fibroblasts were used to test the cell adhesion capacity. The conductive membranes containing HE-doped PPy particles recorded significantly increased electrical stability, cell adhesion, and growth. The electrically more stable and cell adhesive conductive biodegradable membrane may act as a platform for various biomedical applications.     

Surface modification of the polymers present in a polysulfone hollow fiber hemodialyser by covalent binding of heparin or endothelial cell surface heparan sulfate: Flow characteristics and platelet adhesion

The present study addresses the problem of simultaneous surface modification of various polymers, i.e. polysulfone (PSU), polycarbonate (PC), and polyurethane (PU), which constitute the Ultraflux AV 600 S® hollow fibre hemodialyser. An investigation was first made into six different chemical routes aimed at introducing carboxyl groups onto the surface of PSU, PC, and PU model polymers to which heparin (HE) or endothelial cell surface heparan sulfate (ESHS) was covalently bound via the reaction of residual amino groups and a coupling reagent. Carboxyl groups were introduced using three specific reactions based on their nucleophilic or electrophilic introduction into aromatic repeating units of the polymers and three non-specific carboxylation reactions, i.e. UV, heat or redoxactivation via nitrene or radical species. Concentrations of 1-20 nmol COOH groups per cm^-2 led to HE or ESHS surface concentrations corresponding to one or several layers. Two nonspecific carboxylation reactions followed by HE- or ESHS-coupling provided the lowest change in membrane pore structure according to cut off, clearance (urea, phosphate, maltose), ultrafiltration, and diafiltration assessments. In some cases the introduction of excess negatively-charged carboxyl groups and HE improved the flux properties of the modified membranes. The various methods were applied to the dialysis module. Platelet adhesion was not observed in the case of the ESHS-coating of PSU membrane at shear rates of 1050 s^-1, whereas HE and subendothelial matrix showed 56 and 100% coverage, respectively, under similar conditions. The coating of PSU or of other highflux membranes by ESHS appears a promising method for improving membrane properties and to generate biocompatibility characteristics similar to those of natural blood vessels, i.e. inertness to platelet adhesion and no level effects for complement and intrinsic coagulation cascade activation. The ESHS coating may be used without anticoagulants.     

Preparation of poly(acrylic acid) modified polyurethane membrane for biomaterial by UV radiation without degassing.

Poly(acrylic acid) modified polyurethane (AA/PU) membranes were prepared by UV radiation without degassing. The chemical composition of the AA/PU membrane was studied by IR spectroscopy. In addition to those absorption peaks associated with pure PU, the absorption peak at 2400 cm-1 of poly(AA) was also found. The morphology of AA/PU membrane was studied by optical polarizing microscopy. We also measured the glass transition temperature and the decomposition temperature of the AA/PU membrane by differential scanning calorimetry and thermogravimetric analysis. A significant domain was found in the AA/PU membrane, which resulted in different glass transition temperature and decomposition temperature between AA/PU and pure PU membrane. The effect of AA content on the contact angle and water absorption of the AA/PU membrane was determined. It was found that the water content of AA/PU membrane increased with increasing AA content, whereas the contact angle decreased. By using Kaeble's equation and the contact angle data, the surface free energy of AA/PU membrane was determined. The increase of surface free energy resulted from the increase of the dispersion (gammad) term and polar (gammap) term. In order to evaluate the biocompatibility of these membranes, a cytotoxicity test and a cell adhesion and proliferation assay were conducted in cell culture. Immortal cells and primary lymphocytes were both used in this study. The results showed that these AA/PU membranes exhibited very low cytotoxicity and could support cell adhesion and growth. An animal primary test was also done in this study. It was found that the AA/PU membrane could possibly be employed in the treatment of bowel defect.     

Effect of topology of poly(L-lactide-co-ε-caprolactone) scaffolds on the response of cultured human umbilical cord Wharton’s jelly-derived mesenchymal stem cells and neuroblastoma cell lines

In this study, for the first time, a biodegradable poly(L-lactide-co-ε-caprolactone), PLC 67:33 copolymer was developed for use as temporary scaffolds in reconstructive nerve surgery. The effect of the surface topology and pore architecture were studied on the biocompatibility for supporting the growth of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells (hWJ-MSCs) and human neuroblastoma cells (hNBCs) as cell models. Porous PLC membranes were prepared by electrospinning and phase immersion precipitation with particulate leaching and nonporous PLC membranes were prepared by solvent casting. From the results, the porous PLC membranes can support hWJ-MSCs and hNBCs cells better than the nonporous PLC membrane, and the interconnected pore scaffold prepared by electrospinning exhibited a more significant supporting attachment of the cells than the open pore and nonporous membranes. We can consider that these electrospun PLC membranes with 3-D interconnecting fiber networks and a high porosity warrant a potential use as nerve guides in reconstructive nerve surgery.     

Novel Biodegradable Polycaprolactone Occlusion Device Combining Nanofibrous PLGA/Collagen Membrane for Closure of Atrial Septal Defect (ASD)

The purpose of this report was to develop novel biodegradable occlusion devices for closure of atrial septal defects (ASD). To manufacture the biodegradable occluders, polycaprolactone (PCL) components were first fabricated by a lab-scale micro-injection molding machine. They were then assembled and hot-spot welded into double umbrella-like devices of 50 mm in diameter. A special mechanism at the axis of the occluder was designed to self-lock the occluder after the two umbrellas were expanded. Furthermore, a nanofibrous matrix of poly-d-l-lactide-glycolide (PLGA)/type I collagen blend was produced via electrospinning to develop biodegradable and biomimetic anti-shunt membranes for the occluders. Characterization of the biodegradable PCL occluders was carried out. PCL occluders exhibited mechanical properties comparable to that of commercially available Amplatzer occluders. The sealing capability of biodegradable occluders was found superior to that of Amplatzer occluders. In addition, the cell attachment and spreading of endothelial cells seeded on the PLGA/collagen nanofibrous matrix and the interaction between cells and PLGA/collagen nanofibers were studied. The nanofibrous membranes made of PLGA/collagen were very effective in promoting cell proliferation during culture.     

Preparation and Drug-Delivery Potential of Metronidazole-Loaded PELA Tri-block Co-polymeric Electrospun Membranes

The aim of this study was to investigate the potential of poly(ethylene glycol-co-lactide) (PELA tri-block with a segmental sequence of PLA–PEG–PLA) electrospun membranes as drug-delivery vehicles using metronidazole as a model drug. PELA membranes with smooth surfaces and no bead defects were electrospun from polymer solutions containing 20% (w/v) PELA in 8:2 N,N-dimethyl formamide (DMF)/acetone. The morphology of the drug-loaded electrospun membranes was influenced by electrospinning parameters such as the flow rate and voltages during preparation. Metronidazole could be released from the electrospun membranes and was characterized by an initial burst effect. Higher voltages led to faster release rates, while an increase in the flow rate decreased the drug release. The incorporation of metronidazole into the electrospun membranes decreased their surface hydrophilicity. The amount of drug released from the electrospun membranes was effective in inhibiting microbial growth. Cell adhesion on the PELA membranes with or without drug was less than that on the homo-polymeric PDLLA membranes. Proliferation of L929 mouse fibroblasts on the PELA membranes was observed. This study confirms the potential of metronidazole-loaded PELA biodegradable electrospun membranes for optimizing the clinical therapy of post-surgical adhesions and infections.