A tissue engineering approach was developed to produce arbitrary lengths of vascular graft material from smooth muscle and endothelial cells that were derived from a biopsy of vascular tissue. Bovine vessels cultured under pulsatile conditions had rupture strengths greater than 2000 millimeters of mercury, suture retention strengths of up to 90 grams, and collagen contents of up to 50 percent. Cultured vessels also showed contractile responses to pharmacological agents and contained smooth muscle cells that displayed markers of differentiation such as calponin and myosin heavy chains. Tissue-engineered arteries were implanted in miniature swine, with patency documented up to 24 days by digital angiography. (+info)
Outcomes of irradiated polyglactin 910 Vicryl Rapide fast-absorbing suture in oral and scalp wounds.
(2/797)
BACKGROUND: This study evaluated the outcome of wounds closed with irradiated polyglactin 910 (IRPG) Vicryl Rapide (Ethicon, Somerville, N.J.). METHOD: Seventy-one patients with 80 oral wounds and 42 patients with 42 scalp wounds closed with IRPG were evaluated on the day of surgery, then one, seven, 14, 28 and 90 days following surgery. The incidence of inflammation, suppuration and hypertrophic scarring was recorded, along with the timing of spontaneous suture disappearance. This suture material was compared with polytetrafluoroethylene (PTFE) sutures used in dental implant patients, traditional polyglycolic acid (PGLA) sutures used in osteotomy patients and skin staples used in patients with scalp wounds. RESULTS: In the group with intraoral wounds, there were two cases of suppuration with no inflammatory reactions or hypertrophic scarring when IRPG sutures were used, compared to three cases of suppuration with the traditional PGLA sutures. In the group with scalp wounds, there was no suppuration or hypertrophic scarring with IRPG sutures and one inflammatory reaction with skin staples. IRPG sutures never required removal, while all staples, PGLA and PTFE sutures eventually required separate removal. CONCLUSION: Irradiated polyglactin 910 Vicryl Rapide is a useful suture material with both intra- and extraoral applications in the pediatric and adult populations. (+info)
Enhancement of osteogenesis in vitro and in vivo by a novel osteoblast differentiation promoting compound, TAK-778.
(3/797)
TAK-778 [(2R,4S)-(-)-N-(4-diethoxyphosphorylmethylphenyl)-1,2,4, 5-tetrahydro-4-methyl-7, 8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxyamide; mw 505.53], a novel osteoblast differentiation promoting compound, was characterized in vitro and in vivo models. TAK-778 at doses of 10(-6) M and higher promoted potently bone-like nodule formation in the presence of dexamethasone in rat bone marrow stromal cell culture. This was accompanied by increases in cellular alkaline phosphatase activity, soluble collagen release, and osteocalcin secretion. Under the culture conditions, TAK-778 also stimulated the secretion of transforming growth factor-beta and insulin-like growth factor-I, indicating that TAK-778 may exert regulatory effects on osteoblast differentiation via autocrine/paracrine mechanisms. Furthermore, the in vivo osteogenic potential of TAK-778 was studied in bony defect and osteotomy animal models, using sustained release microcapsules consisted of a biodegradable polymer, poly (dl-lactic/glycolic) acid (PLGA). Single local injection of TAK-778/PLGA-microcapsules (PLGA-MC) (0.2-5 mg/site) to rat skull defects resulted in a dose-dependent increase in new bone area within the defects after 4 weeks. When the pellet containing TAK-778/PLGA-MC (4 mg/pellet) was packed into place to fill the tibial segmental defect in rabbit, this pellet induced osseous union within 2 months, whereas the placebo pellet did not. In addition, single local application of TAK-778/PLGA-MC (10 mg/site) to rabbit tibial osteotomy site enhanced callus formation accompanied by an increase in breaking force after 30 days. These results reveal for the first time that a nonendogenous chemical compound promotes potently osteogenesis in vitro and enhances new bone formation during skeletal regeneration and bone repair in vivo and should be useful for the stimulation of fracture healing. (+info)
Bacterial inactivation by using near- and supercritical carbon dioxide.
(4/797)
The three most common methods of sterilization in use today are ethylene oxide exposure, gamma-irradiation, and steam sterilization. Each of these methods has serious limitations for the sterilization of some materials used in medicine, especially thermally and hydrolytically sensitive polymers by themselves and in combination with proteins. In this work, we demonstrate a potential new method of sterilization by using supercritical fluid carbon dioxide. Using this method we achieve complete inactivation of a wide variety of bacterial organisms at moderate temperatures and in the absence of organic solvents or irradiation. Sterilization is a function of both the proximity to the fluid's critical point and the chemical nature of the fluid itself. When biodegradable polymers poly(lactic-co-glycolic) acid and polylactic acid were included in the sterilization process, there was no effect on the inactivation efficiency, yet no physical or chemical damage to these thermally and hydrolytically labile materials was observed. (+info)
Poly-L-lysine improves gene transfer with adenovirus formulated in PLGA microspheres.
(5/797)
In vivo gene transfer with recombinant adenovirus vectors can be hindered by the immunogenicity of the adenovirus capsid proteins. Previous work showed that formulation of the vector with biodegradable polymers such as poly-lactic-glycolic acid (PLGA), polyethylene glycol (PEG), or lipids, may shield the virus from inhibition by neutralizing antibodies. Formulation of adenovirus in PLGA microspheres also allowed for extended release in vitro. In experiments described here, we found that the surfactant used in the formation of the primary emulsion could significantly improve the overall yield of virus released. We also tested the effects of adding poly-L-lysine to adenovirus before encapsulation with PLGA. Our results show that although PLL did not effect the yield of virus encapsulated or released from the microspheres, it significantly improved the efficiency of gene transfer after release from the polymer. (+info)
Enhanced growth of animal and human endothelial cells on biodegradable polymers.
(6/797)
Biodegradable polymers such as poly(L-lactic acid) (PLLA), poly(glycolic acid) (PGA) and PGA coated with PLLA are being employed for cell transplantation and for in vivo regeneration of vascular tissue. Ingrowth and organization of fibrovascular tissue inside polymer scaffolds lead to the occlusion of the regenerated blood vessel. In order to provide regulatory mechanisms to control the development of an inner capsule, endothelialization of these materials is necessary. To achieve this, we employed a novel ammonia plasma technique to surface modified PLLA substrates. Human endothelial cell (HUVEC) and rabbit microvascular endothelial cell (RbMVEC) growth was studied on modified PLLA and control PLLA. Our studies show that modified PLLA and fibronectin (Fn)-coated modified PLLA exhibited statistically significant improvement in HUVEC and RbMVEC growth (P<0.001) when compared to PLLA and Fn-coated PLLA. Therefore, ammonia plasma treatment gives us the unique capability of modifying prosthetic biomaterials of various constructs with the eventual transplantation of mammalian cells to be used in tissue engineering or as biological implants. (+info)
Intraocular pharmacokinetics and safety of a humanized monoclonal antibody in rabbits after intravitreal administration of a solution or a PLGA microsphere formulation.
(7/797)
Poly(lactic-co-glycolic) acid (PLGA) bioresorbable microspheres are used for controlled-release drug delivery and are particularly promising for ocular indications. The objective of the current study was to evaluate the pharmacokinetics and safety of a recombinant human monoclonal antibody (rhuMAb HER2) in rabbits after bolus intravitreal administration of a solution or a PLGA-microsphere formulation. On Day 0, forty-eight male New Zealand white rabbits (2.3-2.6 kg) were immobilized with intramuscular ketamine/xylazine, and the test materials were injected directly into the vitreous compartment. Group 1 animals received rhuMAb HER2 in 50:50 lactide: glycolide PLGA microspheres; Group 2 animals received rhuMAb HER2 in solution (n = 24/group). The dose for each eye was 25 microg (50 microl). After dosing, animals were sacrificed at 2 min, and on 1, 2, 4, 7, 14, 23, 29, 37, 44, 50, and 56 days (n = 2/timepoint/group). Safety assessment included direct ophthalmoscopy, clinical observations, body weight, and hematology and clinical chemistry panels. At necropsy, vitreous and plasma were collected for pharmacokinetics and analysis for antibodies to rhuMAb HER2, and the vitreal pellet (Group 1) was prepared for histologic evaluation. All animals completed the study per protocol-both treatments were well tolerated, and no suppurative or mixed inflammatory cell reaction was observed in the vitreal samples (Group 1) at any of the time points examined. Antibodies to rhuMAb HER2 were detected in plasma samples by Day 7 in both treatment groups, but infrequently in vitreous samples. There were no safety implications associated with this immune response. The in vitro characterization of the PLGA microspheres provided reasonable projections of the in vivo rhuMAb HER2 release kinetics (Group 1). The total amount of antibody that was released was similar in vitro (25.9%) and in vivo (32.4%). RhuMAb HER2 (Group 2) was cleared slowly from the vitreous compartment, with initial and terminal half-lives of 0.9 and 5.6 days, respectively. The volume of distribution approximated the vitreous volume in a rabbit eye. (+info)
Comparison of different methods of intracerebral administration of radioiododeoxyuridine for glioma therapy using a rat model.
(8/797)
The Auger electron emitting agent 5-[125I]iodo-2'-deoxyuridine (i.e. [125I]IUdR) holds promise for the treatment of residual glioma after surgery because this thymidine analogue kills only proliferating cells. However, malignant cells which are not synthesizing DNA during exposure to the radiopharmaceutical will be spared. To determine whether tumour incorporation of [125I]IUdR could be enhanced by protracted administration, we used a C6 cell line, growing in the brains of Wistar rats, as a glioma model and compared three methods of intracerebral delivery of [125I]IUdR. Twenty-four hours after administration of drug, autoradiography of brain sections demonstrated nuclear uptake of the radiopharmaceutical in cells throughout tumour while normal brain cells remained free of radioactivity. The [125I]IUdR labelling indices (% +/- s.e.m.) achieved were 6.2 (0.4) by single injection, 22.5 (4.1) using a sustained release polymer implant (poly(lactide-co-glycolide)) and 34.3 (2.0) by mini-osmotic pump. These results emphasize the need for a sustained delivery system as a prerequisite for effective treatment. These findings are also encouraging for the development of a sustained release system for radiolabelled IUdR for use in the treatment of intracranial tumours, particularly in the immediate postoperative setting. (+info)