Biomedical subjects

Robert A Peattie

Publications and source records attributed to Robert A Peattie.

6 recordsLinked to original sources

PubMed2007

Controlling tissue microenvironments: biomimetics, transport phenomena, and reacting systems.

The reconstruction of tissues ex vivo and production of cells capable of maintaining a stable performance for extended time periods in sufficient quantity for synthetic or therapeutic purposes are primary objectives of tissue engineering. The ability to characterize and manipulate the cellular microenvironment is critical for successful implementation of such cell-based bioengineered systems. As a result, knowledge of fundamental biomimetics, transport phenomena, and reaction engineering concepts is essential to system design and development. Once the requirements of a specific tissue microenvironment are understood, the biomimetic system specifications can be identified and a design implemented. Utilization of novel membrane systems that are engineered to possess unique transport and reactive features is one successful approach presented here. The limited availability of tissue or cells for these systems dictates the need for microscale reactors. A capstone illustration based on cellular therapy for type 1 diabetes mellitus via encapsulation techniques is presented as a representative example of this approach, to stress the importance of integrated systems.

Biological Transport, Active↗

PubMed2007

Perfusion effects and hydrodynamics.

Biological processes within living systems are significantly influenced by the motion of the liquids and gases to which those tissues are exposed. Accordingly, tissue engineers must not only understand hydrodynamic phenomena, but also appreciate the vital role of those phenomena in cellular and physiologic processes both in vitro and in vivo. In particular, understanding the fundamental principles of fluid flow underlying perfusion effects in the organ-level internal environment and their relation to the cellular microenvironment is essential to successfully mimicking tissue behavior. In this work, the major principles of hemodynamic flow and transport are summarized, to provide readers with a physical understanding of these important issues. In particular, since quantifying hemodynamic events through experiments can require expensive and invasive techniques, the benefits that can be derived from the use of computational fluid dynamics (CFD) packages and neural networking (NN) models are stressed. A capstone illustration based on analysis of the hemodynamics of aortic aneurysms is presented as a representative example of this approach, to stress the importance of tissue responses to flow-induced events.

Animals↗

PubMed2006

Stimulation of in vivo angiogenesis using dual growth factor-loaded crosslinked glycosaminoglycan hydrogels.

Crosslinked, chemically modified hyaluronan (HA) hydrogels pre-loaded with two cytokine growth factors, vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1), were employed to elicit new microvessel growth in vivo, in both the presence and absence of heparin (Hp) in the gels. HA hydrogel film samples were surgically implanted in the ear pinnae of mice, and the ears were harvested at 7 or 14 days post-implantation. Analysis of neovascularization showed that each of the treatment groups receiving an implant, except for HA/Hp at day 14, demonstrated significantly more microvessel density than control ears undergoing surgery but receiving no implant (p<0.015). Treatment groups receiving either Ang-1 alone, or aqueous co-delivery of both Ang-1 and VEGF, were statistically unchanged with time. In contrast, film delivery of both growth factors produced continuing increases in vascularization from day 7 to day 14 in the absence of Hp, but decreases in its presence. However, presentation of both VEGF and Ang-1 in crosslinked HA gels containing Hp generated intact microvessel beds with well-defined borders. The HA hydrogels containing Ang-1+VEGF produced the greatest angiogenic response of any treatment group tested at day 14 (NI=7.44 in the absence of Hp and 4.67 in its presence, where NI is a neovascularization index). Even in the presence of Hp, this had 29% greater vessel density than the next largest treatment group receiving HA/Hp+VEGF (NI=3.61, p=0.04). New therapeutic approaches for numerous pathologies could be notably enhanced by the localized, sustained angiogenic response produced by release of both VEGF and Ang-1 from crosslinked HA films.

Angiopoietin-1↗

PubMed2006

Heparin-regulated release of growth factors in vitro and angiogenic response in vivo to implanted hyaluronan hydrogels containing VEGF and bFGF.

Controlled release of human vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) from hydrogels composed of chemically modified hyaluronan (HA) and gelatin (Gtn) was evaluated both in vitro and in vivo. We hypothesized that inclusion of small quantities of heparin (Hp) in these gels would regulate growth factor (GF) release over an extended period, while still maintaining the in vivo bioactivity of released GFs. To test this hypothesis, HA, Gtn, and Hp (15 kDa) were modified with thiol groups, then co-crosslinked with poly (ethylene glycol) diacrylate (PEGDA). Either VEGF or bFGF was incorporated into the gels before crosslinking with PEGDA. Release of these GFs in vitro could be sustained over 42 days by less than 1% Hp content, and was found to decrease monotonically with increasing Hp concentration. As little as 0.03% Hp in the gels reduced the released VEGF fraction from 30% to 21%, while 3% Hp reduced it to 19%. Since the minimum Hp concentration capable of effective controlled GF release in vitro was found to be 0.3% (w/w), this concentration was selected for subsequent in vivo experiments. To evaluate the bioactivity of released GFs in vivo, gel samples were implanted into the ear pinnas of Balb/c mice and the resulting neovascularization response measured. In the presence of Hp, vascularization was sustained over 28 days. GF release was more rapid in vitro from gels containing Gtn than from gels lacking Gtn, though unexpectedly, the in vivo neovascularization response to Gtn-containing gels was decreased. Nevertheless significant numbers of neovessels were generated. The ability to stimulate localized microvessel growth at controlled rates for extended times through the release of GFs from covalently linked, Hp-supplemented hydrogels will ultimately provide a powerful therapeutic tool.

Angiogenesis Inducing Agents↗

PubMed2005

Dual growth factor-induced angiogenesis in vivo using hyaluronan hydrogel implants.

Crosslinked hyaluronan (HA) hydrogels preloaded with two cytokine growth factors, vascular endothelial growth factor (VEGF) and keratinocyte growth factor (KGF), were employed to elicit new microvessel growth in vivo. As a major glycosaminoglycan (GAG) component of extracellular matrix (ECM), HA is an excellent biopolymeric building block for new biomimetic, biocompatible therapeutic materials. HA hydrogel film samples were surgically implanted in the ear pinnae of mice, and the ears were harvested at 7 or 14 days post-implantation. Histologic analysis showed that each of the groups receiving an implant demonstrated significantly more microvessel density than control ears undergoing surgery but receiving no implant (p<0.001). Treatment groups receiving either co-delivery of both KGF and VEGF, an HA hydrogel lacking a growth factor or HA hydrogels containing a single cytokine were statistically unchanged with time, whereas treatment with KGF alone produced continuing increases in vascularization from day 7 to day 14. Strikingly, presentation of both VEGF and KGF in crosslinked HA generated intact microvessel beds with well-defined borders. In addition, an additive response to co-delivery of both cytokines in the HA hydrogel was observed. The HA hydrogels containing KGF+VEGF produced the greatest angiogenic response of any treatment group tested (NI=5.4 at day 14, where NI is a neovascularization index). This was 33% greater vessel density than in the next largest treatment group, that received HA+KGF (NI=4.0, p<0.002). New therapeutic approaches for numerous pathologies could be notably enhanced by the localized, sustained angiogenic response produced by release of both VEGF and KGF from crosslinked HA films.

Angiogenesis Inducing Agents↗

PubMed2004

Pulsatile flow in fusiform models of abdoiminal aortic aneurysms: flow fields, velocity patterns and flow-induced wall stresses.

As one important step in the investigation of the mechanical factors that lead to rupture of abdominal aortic aneurysms, flow fields and flow-induced wall stress distributions have been investigated in model aneurysms under pulsatile flow conditions simulating the in vivo aorta at rest. Vortex pattern emergence and evolution were evaluated, and conditions for flow stability were delineated. Systolic flow was found to be forward-directed throughout the bulge in all the models, regardless of size. Vortices appeared in the bulge initially during deceleration from systole, then expanded during the retrograde flow phase. The complexity of the vortex field depended strongly on bulge diameter In every model, the maximum shear stress occurred at peak systole at the distal bulge end, with the greatest shear stress developing in a model corresponding to a 4.3 cm AAA in vivo. Although the smallest models exhibited stable flow throughout the cycle, flow in the larger models became increasingly unstable as bulge size increased, with strong amplification of instability in the distal half of the bulge. These data suggest that larger aneurysms in vivo may be subject to more frequent and intense turbulence than smaller aneurysms. Concomitantly, increased turbulence may contribute significantly to wall stress magnitude and thereby to risk of rupture.

Animals↗