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At least 253 records · Page 14Linked to original sources
PubMed2000

Transpecies heart valve transplant: advanced studies of a bioengineered xeno-autograft.

BACKGROUND: Tissue engineering approaches utilizing biomechanically suitable cell-conductive matrixes should extend xenograft heart valve performance, durability, and growth potential to an extent presently attained only by the pulmonary autograft. To test this hypothesis, we developed an acellular, unfixed porcine aortic valve-based construct. The performance of this valve has been evaluated in vitro under simulated aortic conditions, as a pulmonary valve replacement in sheep, and in aortic and pulmonary valve replacement in humans. METHODS: SynerGraft porcine heart valves (CryoLife Inc, Kennesaw, GA) were constructed from porcine noncoronary aortic valve cusp units consisting of aorta, noncoronary aortic leaflet, and attached anterior mitral leaflet (AML). After treatment to remove all histologically demonstrable leaflet cells and substantially reduce porcine cell-related immunoreactivity, three valve cusps were matched and sewn to form a symmetrical root utilizing the AML remnants as the inflow conduit. SynerGraft valves were evaluated by in vitro hydrodynamics, and by in vivo implants in the right ventricular outflow tract of weanling sheep for up to 336 days. Cryopreserved allograft valves served as control valves in both in vitro and in vivo evaluations. Valves were also implanted as aortic valve replacements in humans. RESULTS: In vitro pulsatile flow testing of the SynerGraft porcine valves demonstrated excellent valve function with large effective orifice areas and low gradients equivalent to a normal human aortic valve. Implants in sheep right ventricular outflow tracts showed stable leaflets with up to 80% of matrix recellularization with host fibroblasts and/or myofibroblasts, and with no leaflet calcification over 150 days, and minimal deposition at 336 days. Echocardiography studies showed normal hemodynamic performance during the implantation period. The human implants have proven functional for over 9 months. CONCLUSIONS: A unique heart valve construct has been engineered to achieve the equivalent of an autograft. Short-term durability of these novel implants demonstrates for the first time the possibility of an engineered autograft.

Animals↗
PubMed2000

Construction of a bioengineered cardiac graft.

OBJECTIVES: Currently available graft materials for repair of congenital heart defects cause significant morbidity and mortality because of their lack of growth potential. An autologous cell-seeded graft may improve patient outcomes. We report our initial experience with the construction of a biodegradable graft seeded with cultured rat or human cells and identify their 3-dimensional growth characteristics. METHODS: Fetal rat ventricular cardiomyocytes, stomach smooth muscle cells, skin fibroblasts, and adult human atrial and ventricular cardiomyocytes were isolated and cultured in vitro. These cells were injected into or laid onto biodegradable gelatin meshes, and their rate of proliferation and spatial location within the mesh was evaluated by using a cell counter and histologic analysis. RESULTS: Rat cardiomyocytes, smooth muscle cells, and fibroblasts demonstrated steady proliferation over 3 to 4 weeks. The gelatin mesh was slowly degraded, but this process was most rapid after seeding with fibroblasts. Human atrial cardiomyocytes proliferated within the gelatin meshes but at a slower rate than that of fetal rat cardiomyocytes. Human ventricular cardiomyocytes survived within the gelatin mesh matrix but did not increase in number during the 2-week duration of evaluation. Grafts seeded with rat ventricular cells exhibited spontaneous rhythmic contractility. All cell types preferentially migrated to the uppermost surface of each graft and formed a 300- to 500-microm thick layer. CONCLUSIONS: Fetal rat ventricular cardiomyocytes, gastric smooth muscle cells, skin fibroblasts, and adult human atrial cardiomyocytes can grow in a 3-dimensional pattern within a biodegradable gelatin mesh. Similar autologous cell-seeded constructs may eventually be applied to repair congenital heart defects.

Adult↗
PubMed1996

Bioengineering seeds of contemplation: a private practitioner's perspective.

In a precise semantic sense, the most significant biomaterial in dentistry is the human tooth. How it reacts, changes and is affected during the dynamics of occlusal loading should be reexamined in light of modern technology. Much is known about the embryology, histology, biochemistry, anatomy, and the microbiology affecting teeth; however, there are areas of biomechanics, biochemistry, and bioelectricity which also affect dental hard tissues that remain largely unexplored. Technological advances enable us to use more sophisticated instrumentation to measure and quantify changes that occur during the dynamics of occlusal activity. Armed with this information, dentistry can better understand how teeth interact with restorative materials in order to increase the longevity of both.

Biomechanical Phenomena↗
PubMed1998

The development of bioengineered skin.

Driven by the need for donor tissue for patients suffering from extensive burns, alternatives to autologous and cadaver-derived tissue have been under development for the past 20 years. Unilayered and bilayered models representing the skin's epidermal and/or dermal components have been developed using both cells and matrix materials. In addition to their use in patients with extensive burns, trials using these products on refractory and challenging patients with both acute and chronic wounds have led to the commercial availability of some of these products.

Cell Transplantation↗
PubMed2002

Artificial mammalian gene regulation networks-novel approaches for gene therapy and bioengineering.

Recently developed strategies for targeted molecular interventions in mammalian cells have created novel opportunities in biotechnological and biomedical research with huge economic and therapeutic impact: the design of mammalian cells with desired phenotypes for biopharmaceutical manufacturing, tissue engineering and gene therapy. These advances have been enabled by constructing artificial gene regulation systems with control modalities similar to those evolved in key regulatory networks of mammalian cells. This review highlights recurring cellular regulation strategies and artificial gene regulation technology currently in use for rational reprogramming of cellular key events including metabolism, growth, differentiation and cell death to achieve sophisticated bioprocess and therapeutic goals.

Animals↗
PubMed1999

The relationship between elevated interstitial fluid pressure and blood flow in tumors: a bioengineering analysis.

PURPOSE: To examine the hypothesis that elevated interstitial fluid pressure (IFP) is a cause of reduced blood flow in tumors. MATERIALS AND METHODS: A physiologic model of tumor blood flow was developed based on a semipermeable, compliant capillary in the center of a spherical tumor. The model incorporates the interaction between the tumor vasculature and the interstitium, as mediated by IFP. It also incorporates the dynamic behavior of the capillary wall in response to changes in transmural pressure, and the effect of viscosity on blood flow. RESULTS: The model predicted elevated tumor IFP in the range of 0 to 56 mmHg. The capillary diameter in the setting of elevated IFP was greatest at the arterial end, and constricted to between 3.2 and 4.4 microm at the venous end. This corresponded to a 2.4- to 3.5-fold reduction in diameter along the length of the capillary. The IFP exceeded the intravascular pressure distally in the capillary, but vascular collapse did not occur. Capillary diameter constriction resulted in a 2.3- to 9.1-fold steady-state reduction in tumor blood flow relative to a state of near-zero IFP. CONCLUSION: The results suggest that steady-state vascular constriction occurs in the setting of elevated IFP, and leads to reduced tumor blood flow. This may in turn contribute to the development of hypoxia, which is an important cause of radiation treatment failure in many tumors.

Blood Pressure↗
PubMed2000

Camouflaged blood cells: low-technology bioengineering for transfusion medicine?

The small number of studies done on the covalent modification of RBC with PEG, or PEG-derivatives, suggests that the immunocamouflage of intact cells significantly reduces the antigenicity and immunogenicity of the foreign cell. Importantly, this protective immunologic effect can be accomplished without adversely affecting the structure, function, or viability of the modified cell (e.g., RBCs and lymphocytes). As a consequence, PEG-RBC may have significant practical value in the treatment of the chronically transfused patient as a prophylactic measure against allosensitization. The PEG-RBC also may be useful in treating the already allosensitized individual. As shown, preexisting antibodies do not effectively recognize nor bind to the modified donor cells. A finding of further interest to transfusion medicine is that pegylation of contaminating lymphocytes within RBC products may prove efficacious in preventing graft-versus-host disease in the immunocompromised patient. However, the main emphasis of our research continues to be the immunocamouflage of RBC for use in chronic transfusion therapy of the SCD and thalassemic patient.

Blood Component Transfusion↗
PubMed2003

Development of combinatorial bioengineering using yeast cell surface display--order-made design of cell and protein for bio-monitoring.

A genetic system to display proteins as their active and functional forms on the cell surface of yeast, Saccharomyces cerevisiae, has been exploited. Surface-engineered (arming) cells displaying amylase or cellulase could assimilate starch or cellulose as the sole carbon source, although S. cerevisiae can not intrinsically assimilate them. Arming cells with a green fluorescent protein (GFP) from Aequorea victoria can emit green fluorescence from the cell surface in response to the environmental conditions. From these results, we attempted to construct a system to monitor the foreign protein production in yeast by simultaneous displaying the enhanced GFP (EGFP). The expression in yeast of the Escherichia coli beta-galactosidase-encoding gene was examined as an example of intracellular production and that of the human interferon-alpha (omega, IFN-omega)-encoding gene as an example of extracellular production. Their productions and the simultaneous surface-display of EGFP as a reporter were controlled by the same promoter, GAL1. The relationship among fluorescence signals and their productions was evaluated. The surface-display system, unlike one using tag-proteins, would be able to facilitate the monitoring of native protein productions in bioprocesses using living cells in real time by the combination of promoters and GFP variants.

Biomedical Engineering↗
PubMed2003

Antisense technology in molecular and cellular bioengineering.

Antisense technology is finding increasing application not only in clinical development, but also for cellular engineering. Several types of antisense methods (e.g. antisense oligonucleotides, antisense RNA and small interfering RNA) can be used to inhibit the expression of a target gene. These antisense methods are being used as part of metabolic engineering strategies to downregulate enzymes controlling undesired pathways with regard to product formation. In addition, they are beginning to be utilized to control cell phenotype in tissue engineering constructs. As improved methods for antisense effects that can be externally regulated emerge, these approaches are likely to find increased application in cellular engineering applications.

Animals↗