Advanced Technologies and Regenerative Medicine
Advanced Technologies and Regenerative Medicine
Hardy P.A.,University of Kentucky |
Keeley D.,Advanced Technologies and Regenerative Medicine |
Schorn G.,Codman and Shurtleff |
Forman E.,University of Kentucky |
And 4 more authors.
Journal of Neuroscience Methods | Year: 2013
Convection enhanced delivery (CED) is a powerful method of circumventing the blood-brain barrier (BBB) to deliver therapeutic compounds directly to the CNS. While inferring the CED distribution of a therapeutic compound by imaging a magnetic resonance (MR)-sensitive tracer has many advantages, however how the compound distribution is affected by the features of the delivery system, its target tissue, and its molecular properties, such as its binding characteristics, charge, and molecular weight (MW) are not fully understood. We used MR imaging of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)-tagged polylysine compounds of various MW, in vitro and in vivo, to measure the dependence of compounds MW on CED distribution. For the in vitro studies, the correlation between volume of distribution (Vd) as a function of MW was determined by measuring the T1 of the infused tracers, into 0.6% agarose gels through a multiport catheter. The compounds distributed in the gels inversely proportional to their MW, consistent with convection and unobstructed diffusion through a porous media. For the in vivo studies, Gd-DTPA tagged compounds were infused into the non-human primate putamen, via an implanted multiport catheter connected to a MedStream™ pump, programmed to deliver a predetermined volume with alternating on-off periods to take advantage of the convective and diffusive contributions to Vd. Unlike the gel studies, the higher MW polylysine-tracer infusions did not freely distribute from the multiport catheter in the putamen, suggesting that distribution was impeded by other properties that should also be considered in future tracer design and CED infusion protocols. © 2013 Elsevier B.V.
Hamid Q.,Drexel University |
Snyder J.,Drexel University |
Wang C.,Drexel University |
Timmer M.,Advanced Technologies and Regenerative Medicine |
And 4 more authors.
Biofabrication | Year: 2011
In the field of biofabrication, tissue engineering and regenerative medicine, there are many methodologies to fabricate a building block (scaffold) which is unique to the target tissue or organ that facilitates cell growth, attachment, proliferation and/or differentiation. Currently, there are many techniques that fabricate three-dimensional scaffolds; however, there are advantages, limitations and specific tissue focuses of each fabrication technique. The focus of this initiative is to utilize an existing technique and expand the library of biomaterials which can be utilized to fabricate three-dimensional scaffolds rather than focusing on a new fabrication technique. An expanded library of biomaterials will enable the precision extrusion deposition (PED) device to construct three-dimensional scaffolds with enhanced biological, chemical and mechanical cues that will benefit tissue generation. Computer-aided motion and extrusion drive the PED to precisely fabricate micro-scaled scaffolds with biologically inspired, porosity, interconnectivity and internal and external architectures. The high printing resolution, precision and controllability of the PED allow for closer mimicry of tissues and organs. The PED expands its library of biopolymers by introducing an assisting cooling (AC) device which increases the working extrusion temperature from 120 to 250 °C. This paper investigates the PED with the integrated AC's capabilities to fabricate three-dimensional scaffolds that support cell growth, attachment and proliferation. Studies carried out in this paper utilized a biopolymer whose melting point is established to be 200 °C. This polymer was selected to illustrate the newly developed device's ability to fabricate three-dimensional scaffolds from a new library of biopolymers. Three-dimensional scaffolds fabricated with the integrated AC device should illustrate structural integrity and ability to support cell attachment and proliferation. © 2011 IOP Publishing Ltd.
Cole B.J.,Rush University Medical Center |
Farr J.,OrthoIndy |
Winalski C.S.,Cleveland Clinic |
Hosea T.,Robert Wood Johnson Medical School |
And 3 more authors.
American Journal of Sports Medicine | Year: 2011
Background: There are currently several approaches being pursued to treat focal defects of articular cartilage, each having specific advantages or challenges. A single-stage procedure that uses autologous cartilage fragments, Cartilage Autograft Implantation System (CAIS), is being evaluated in patients and may offer a clinically effective option. Purpose: To establish the safety of CAIS and to test whether CAIS improves quality of life by using standardized outcomes assessment tools. Study Design: Randomized controlled trial; Level of evidence, 2.Methods: Patients (n = 29) were randomized (1:2) with the intent to treat with either a control (microfracture [MFX]) or an experimental (CAIS) procedure. Patients were followed at predetermined time points for 2 years using several standardized outcomes assessment tools (SF-36, International Knee Documentation Committee [IKDC], Knee injury and Osteoarthritis Outcome Score [KOOS]). Magnetic resonance imaging was performed at baseline, 3 weeks, and 6, 12, and 24 months. Results: Lesion size and International Cartilage Repair Society (ICRS) grade were similar in both groups. General outcome measures (eg, physical component score of the SF-36) indicated an overall improvement in both groups, and no differences in the number of adverse effects were noted in comparisons between the CAIS and MFX groups. The IKDC score of the CAIS group was significantly higher (73.9 ± 14.72 at 12 months and 82.95 ± 14.88 at 24 months) compared with the MFX group (57.78 ± 18.31 at 12 months and 59.5 ± 13.44 at 24 months). Select subdomains (4/5) in the KOOS instrument were significantly different at 12 and 18 months, and all subdomains (Symptoms and Stiffness, Pain, Activities of Daily Living, Sports and Recreation, Knee-related Quality of Life) were significantly increased at 24 months in CAIS with scores of 88.47 ± 11.68, 90.64 ± 7.87, 97.29 ± 3.8, 78.16 ± 22.06, and 69 ± 23.15 compared with 75 ± 9.31, 78.94 ± 13.73, 89.46 ± 8.13, 51.67 ± 26.01, and 37.15 ± 21.67 in the MFX group. These significant improvements were maintained at 24 months in both IKDC and KOOS. Qualitative analysis of the imaging data did not note differences between the 2 groups in fill of the graft bed, tissue integration, or presence of subchondral cysts. Patients treated with MFX had a significantly higher incidence of intralesional osteophyte formation (54% and 70% of total number of lesions treated) at 6 and 12 months when compared with CAIS (8% and 25% of total number of lesions treated).Conclusion: The first clinical experience in using CAIS for treating patients with focal chondral defects indicates that it is a safe, feasible, and effective method that may improve long-term clinical outcomes. © 2011 The Author(s).
Dave V.,Cordis Corporation |
Buensuceso C.,Advanced Technologies and Regenerative Medicine |
Colter D.,Advanced Technologies and Regenerative Medicine |
Zhao J.,Cordis Corporation |
Falotico R.,Cordis Corporation
Materials Research Society Symposium Proceedings | Year: 2010
Flat coupons prepared from cobalt chromium alloy (CoCr) were modified using different methods (low energy excimer laser processing, electron beam irradiation, and immobilized covalently-bound heparin coating). Human coronary artery endothelial cell (HCAEC) attachment and growth kinetics were investigated on unmodified and modified metal surfaces. Results showed that HCAEC attach to unmodified CoCr coupons and surface-modified CoCr coupons. No change in cell number was observed when cells were grown on CoCr coupons and heparin coated coupons throughout the 72h study period. A decrease in cell number was observed for excimer treated coupons. HCAEC seeding on CoCr stents indicated that cells attached and proliferated on the stents over a ten day study period. This research showed that physical modifications did not improve cell proliferation. Very few non-viable cells were observed for unmodified and surface bound heparin coupons, and cells attached to the surface up to 72h. This study shows that heparin covalently coated on a stent surface to provide anti-thrombotic properties did not generate any negative effect on cell attachment and proliferation. In vitro screening method of testing endothelial cell attachment and proliferation on modified metal stent surfaces can be used to gain insight for developing next generation drug eluting stents with improved endothelialization behavior. © 2010 Materials Research Society.
Tyler B.,Johns Hopkins Hospital |
Wadsworth S.,Advanced Technologies and Regenerative Medicine |
Recinos V.,Johns Hopkins Hospital |
Mehta V.,Johns Hopkins Hospital |
And 11 more authors.
Neuro-Oncology | Year: 2011
Rapamycin, an anti-proliferative agent, is effective in the treatment of renal cell carcinoma and recurrent breast cancers. We proposed that this potent mammalian target of rapamycin inhibitor may be useful for the treatment of gliomas as well. We examined the cytotoxicity of rapamycin against a rodent glioma cell line, determined the toxicity of rapamycin when delivered intracranially, and investigated the efficacy of local delivery of rapamycin for the treatment of experimental malignant glioma in vivo. We also examined the dose-dependent efficacy of rapamycin and the effect when locally delivered rapamycin was combined with radiation therapy. Rapamycin was cytotoxic to 9L cells, causing 34% growth inhibition at a concentration of 0.01 μg/ mL. No in vivo toxicity was observed when rapamycin was incorporated into biodegradable caprolactone-glycolide (35:65) polymer beads at 0.3%, 3%, and 30% loading doses and implanted intracranially. Three separate efficacy studies were performed to test the reproducibility of the effect of the rapamycin beads as well as the validity of this treatment approach. Animals treated with the highest dose of rapamycin beads tested (30%) consistently demonstrated significantly longer survival durations than the control and placebo groups. All doseescalating rapamycin bead treatment groups (0.3%, 3% and 30%), treated both concurrently with tumor and in a delayed manner after tumor placement, experienced a significant increase in survival, compared with controls. Radiation therapy in addition to the simultaneous treatment with 30% rapamycin beads led to significantly longer survival duration than either therapy alone. These results suggest that the local delivery of rapamycin for the treatment of gliomas should be further investigated. © 2011 The Author(s).
Dai W.-G.,Johnson and Johnson Pharmaceutical Research and Development |
Dong L.C.,ADDS Pharmaceuticals |
Creasey A.A.,Advanced technologies and regenerative medicine
Pharmaceutical Technology | Year: 2011
The authors sought to identify a precipitation inhibitor for Labrasol formulations that include poorly water-soluble drugs. Two low solubility compounds were combined with Pluronic F127, polyethylene glycol 400, and N-methyl-2- pyrrolidone. The study results suggested that Pluronic F127 might be a potent inhibitor of drug precipitation for Labrasol formulations.