Effects of crude oil on phospholipid fatty acid compositions of marine hydrocarbon degraders: estimation of the bacterial membrane fluidity

In this study, we investigated, in vitro, the effects of petroleum hydrocarbons on the phospholipid ester-linked fatty acid composition of Corynebacterium sp. Strain 8. The usual ratio of monounsaturated fatty acids E/Z (or trans/cis) was calculated. This ratio led to unexpected results because we found similar values for growths on either a hydrophobic substrate (crude oil) or a soluble carbon source (rich medium). The use of such an indicator seemed limited for monitoring an environmental stress, so we proposed an index based on the homeoviscous adaptation theory. A membrane viscosity index was defined and applied to Corynebacterium sp. Strain 8 (in vitro growth) and to a sedimentary community (in situ experiment). The results allowed us to estimate the membrane fluidity of both an isolated strain and a bacterial community in accordance with the medium hydrophobicity.     

Comparative Study on Osteoconductivity by Synthetic Octacalcium Phosphate and Sintered Hydroxyapatite in Rabbit Bone Marrow

Octacalcium phosphate (OCP) is thought to be a precursor of the mineral crystals in biological apatite. Synthetic OCP has been shown to be converted into an apatite structure when implanted in murine calvarial bone, to enhance bone regeneration more than synthetic hydroxyapatite (HA), and to degrade faster than biodegradable β-tricalcium phosphate. This study was designed to investigate whether OCP implantation enhances the formation and resorption of new bone (remodeling) concomitant with OCP degradation when implanted intramedullary in a rabbit femur for 12 weeks, compared to sintered HA ceramic. Histological and histomorphometric analyses using undecalcified specimens showed that the area of bone apposition was significantly higher on OCP than on HA between 2 and 3 weeks, whereas it subsequently became smaller on OCP than on HA. The area attacked by multinucleated giant cells, including tartrate-resistant acid phosphatase (TRAP)-positive cells, was significantly higher for OCP than for HA at 8 weeks. Radiography revealed resorption of OCP but not of HA. The results disclose some osteoconductive characteristics of synthetic OCP in the bone marrow space: (1) enhancement of bone regeneration at the initial bone apposition stage and (2) stimulation of resorption of the newly formed bone coupled with OCP biodegradation mediated by TRAP-positive osteoclast-like cells. These results suggest that synthetic OCP would be a more useful bone substitute than HA in implant applications where rapid bone formation and concomitant implant resorption are important considerations.     

聚乳酸微球的体外降解

目的:研究聚乳酸微球降解的规律及机制.方法:用5种方法研究聚乳酸微球降解过程:扫描电子显微镜观察微球表面形态;测定失重;凝胶渗透色谱法测定聚合物的平均相对分子质量;测定pH;紫外分光光度法测定乳酸含量.结果:聚乳酸的降解过程有两个阶段,初期主要发生聚合物分子链断裂,后期主要发生聚合物片段溶蚀.其降解速度随平均相对分子质量增加而减慢.结论:聚乳酸是可生物降解材料,降解有规律,是优良的药物控释材料.     

Biodegradable and amphiphilic block copolymer–doxorubicin conjugate as polymeric nanoscale drug delivery vehicle for breast cancer therapy

Polymeric nanoparticles have shown great promise as attractive vehicles for drug delivery. In this study, we designed, prepared and characterized biodegradable amphiphilic triblock HPMA copolymer–doxorubicin (copolymer–DOX) conjugate based nanoparticle as enzyme-sensitive drug delivery vehicle. The enzyme-sensitive peptide GFLGKGLFG was introduced to the main chain of the copolymer with hydrophilic and hydrophobic blocks. The triblock HPMA polymer–DOX conjugate with high molecules (Mw 90 kDa) can be degraded to product with low molecule weight (Mw 44 kDa) below the renal threshold. The copolymer–DOX conjugate can self-assemble into compact nanoparticle, which was characterized by scanning electron microscope (SEM) and atomic force microscope (AFM) studies. This polymeric nanoparticle substantially enhanced antitumor efficacy compared to the free DOX, exhibiting much higher effects on inhibiting proliferation and inducing apoptosis on the 4T1 murine breast cancer model confirmed by the evidences from mice weight shifts, tumor growth curves, tumor growth inhibition (TGI), immunohistochemical analysis and histological assessment. The in vivo toxicity evaluation demonstrated that the polymeric nanoparticle reduced DOX-induced toxicities and presented no significant side effects to normal organs of both tumor bearing and healthy mice as measured by body weight shift, blood routine test and histological analysis. Therefore, the triblock HPMA copolymer–DOX conjugate based nanoparticle is promising as a potential drug delivery vehicle for breast cancer therapy.     

Effect of addition of hyaluronic acids on the osteoconductivity and biodegradability of synthetic octacalcium phosphate

The present study was designed to investigate whether three sodium hyaluronic acid (HyA) medical products, Artz®, Suvenyl® and a chemically modified derivative of sodium HyA Synvisc®, can be used as suitable vehicles for an osteoconductive octacalcium phosphate (OCP). OCP granules (300–500 μm diameter) were mixed with these sodium HyAs with molecular weights of 90 × 10⁴ (Artz®), 190 × 10⁴ (Suvenyl®) and 600 × 10⁴ (Synvisc®) (referred to as HyA90, HyA190 and HyA600, respectively). OCP–HyA composites were injected using a syringe into a polytetrafluoroethylene ring, placed on the subperiosteal region of mouse calvaria for 3 and 6 weeks, and then bone formation was assessed by histomorphometry. The capacity of the HyAs for osteoclast formation from RAW264 cells with RANKL was examined by TRAP staining in vitro. Bone formation was enhanced by the OCP composites with HyA90 and HyA600, compared to OCP alone, through enhanced osteoclastic resorption of OCP. HyA90 and HyA600 facilitated in vitro osteoclast formation. The results suggest that the osteoconductive property of OCP was accelerated by the HyAs-associated osteoclastic resorption of OCP, and therefore that HyA/OCP composites are attractive bone substitutes which are injectable and bioactive materials.     

Semi-degradable poly(β-amino ester) networks with temporally controlled enhancement of mechanical properties

Biodegradable polymers are clinically used in numerous biomedical applications, and classically show a loss of mechanical properties within weeks of implantation. This work demonstrates a new class of semi-degradable polymers that show an increase in mechanical properties through degradation via a controlled shift in a thermal transition. Semi-degradable polymer networks, poly(β-amino ester)-co-methyl methacrylate, were formed from a low glass transition temperature crosslinker, poly(β-amino ester), and high glass transition temperature monomer, methyl methacrylate, which degraded in a manner dependent upon the crosslinker chemical structure. In vitro and in vivo degradation revealed changes in mechanical behavior due to the degradation of the crosslinker from the polymer network. This novel polymer system demonstrates a strategy to temporally control the mechanical behavior of polymers and to enhance the initial performance of smart biomedical devices.     

A porous tissue engineering scaffold selectively degraded by cell-generated reactive oxygen species

Biodegradable tissue engineering scaffolds are commonly fabricated from poly(lactide-co-glycolide) (PLGA) or similar polyesters that degrade by hydrolysis. PLGA hydrolysis generates acidic breakdown products that trigger an accelerated, autocatalytic degradation mechanism that can create mismatched rates of biomaterial breakdown and tissue formation. Reactive oxygen species (ROS) are key mediators of cell function in both health and disease, especially at sites of inflammation and tissue healing, and induction of inflammation and ROS are natural components of the in vivo response to biomaterial implantation. Thus, polymeric biomaterials that are selectively degraded by cell-generated ROS may have potential for creating tissue engineering scaffolds with better matched rates of tissue in-growth and cell-mediated scaffold biodegradation. To explore this approach, a series of poly(thioketal) (PTK) urethane (PTK-UR) biomaterial scaffolds were synthesized that degrade specifically by an ROS-dependent mechanism. PTK-UR scaffolds had significantly higher compressive moduli than analogous poly(ester urethane) (PEUR) scaffolds formed from hydrolytically-degradable ester-based diols (p < 0.05). Unlike PEUR scaffolds, the PTK-UR scaffolds were stable under aqueous conditions out to 25 weeks but were selectively degraded by ROS, indicating that their biodegradation would be exclusively cell-mediated. The in vitro oxidative degradation rates of the PTK-URs followed first-order degradation kinetics, were significantly dependent on PTK composition (p < 0.05), and correlated to ROS concentration. In subcutaneous rat wounds, PTK-UR scaffolds supported cellular infiltration and granulation tissue formation, followed first-order degradation kinetics over 7 weeks, and produced significantly greater stenting of subcutaneous wounds compared to PEUR scaffolds. These combined results indicate that ROS-degradable PTK-UR tissue engineering scaffolds have significant advantages over analogous polyester-based biomaterials and provide a robust, cell-degradable substrate for guiding new tissue formation.     

Intra-articular administration of gelatin hydrogels incorporating rapamycin–micelles reduces the development of experimental osteoarthritis in a murine model

Autophagy is a cellular homeostasis mechanism that may have a protective role against osteoarthritis (OA). The present study investigated the therapeutic effect of local administration of rapamycin, a potent activator of autophagy, against OA. To achieve controlled intra-articular administration of rapamycin, gelatin hydrogels incorporating rapamycin-micelles were created and the release profile was evaluated in vitro. The therapeutic effects of gelatin hydrogels incorporating rapamycin-micelles were then tested in a murine OA model. Mice were divided into four groups: Group 1, gelatin hydrogels alone; Group 2, single injection of 1 μg rapamycin; and Groups 3 and 4, gelatin hydrogels incorporating 100 ng or 1 μg rapamycin-micelles, respectively. Immunohistochemical analysis revealed that autophagic marker-positive chondrocytes were increased in the rapamycin-treated mice at 10 weeks after surgery. The histologic score was better in Groups 3 and 4 than in Groups 1 and 2, and Group 2 had a better score than Group 1. Delayed OA progression was maintained even at 16 weeks after surgery in Group 4. Microarray and real-time polymerase chain reaction analysis indicated that OA mediator genes were downregulated in the rapamycin-treated mice. Our novel system for intra-articular administration of rapamycin could be a novel therapeutic approach for treating patients with OA.     

Antimicrobial antidegradative dental adhesive preserves restoration-tooth bond

ObjectiveAssess the ability of an antimicrobial drug-releasing resin adhesive, containing octenidine dihydrochloride (OCT)-silica co-assembled particles (DSPs), to enhance the biostability and preserve the interfacial fracture toughness (FT) of composite restorations bonded to dentin. Enzyme-catalyzed degradation compromises the dental restoration-tooth interface, increasing cariogenic bacterial infiltration. In addition to bacterial ingress inhibition, antimicrobial-releasing adhesives may exhibit direct interfacial biodegradation inhibition as an additional benefit.MethodsMini short-rod restoration bonding specimens with total-etch adhesive with/without 10% wt. DSPs were made. Interfacial fracture toughness (FT) was measured as-manufactured or post-incubation in simulated human salivary esterase (SHSE) for up to 6-months. Effect of OCT on SHSE and whole saliva/bacterial enzyme activity was assessed. Release of OCT outside the restoration interface was assessed.ResultsNo deleterious effect of DSPs on initial bonding capacity was observed. Aging specimens in SHSE reduced FT of control but not DSP-adhesive-bonded specimens. OCT inhibited SHSE degradation of adhesive monomer and may inhibit endogenous proteases. OCT inhibited bacterial esterase and collagenase. No endogenous collagen breakdown was detected in the present study. OCT increased human saliva degradative esterase activity below its minimum inhibitory concentration towards S. mutans (MIC), but inhibited degradation above MIC. OCT release outside restoration margins was below detection.SignificanceDSP-adhesive preserves the restoration bond through a secondary enzyme-inhibitory effect of released OCT, which is virtually confined to the restoration interface microgap. Enzyme activity modulation may produce a positive-to-negative feedback switch, by increasing OCT concentration via biodegradation-triggered release to an effective dose, then subsequently slowing degradation and degradation-triggered release.     

Single and dual crosslinked oxidized methacrylated alginate/PEG hydrogels for bioadhesive applications

A degradable, cytocompatible bioadhesive can facilitate surgical procedures and minimize patient pain and post-surgical complications. In this study a bioadhesive hydrogel system based on oxidized methacrylated alginate/8-arm poly(ethylene glycol) amine (OMA/PEG) has been developed, and the bioadhesive characteristics of the crosslinked OMA/PEG hydrogels evaluated. Here we demonstrate that the swelling behavior, degradation profiles, and storage moduli of crosslinked OMA/PEG hydrogels are tunable by varying the degree of alginate oxidation. The crosslinked OMA/PEG hydrogels exhibit cytocompatibility when cultured with human bone marrow-derived mesenchymal stem cells. In addition, the adhesion strength of these hydrogels, controllable by varying the alginate oxidation level and measured using a porcine skin model, is superior to commercially available fibrin glue. This OMA/PEG hydrogel system with controllable biodegradation and mechanical properties and adhesion strength may be a promising bioadhesive for clinical use in biomedical applications, such as drug delivery, wound closure and healing, biomedical device implantation, and tissue engineering.