Development of Novel Biodegradable Polymer Scaffolds for Vascular Tissue Engineering

Gui, Liqiong; Zhao, Liping; Spencer, Randal W.; Burghouwt, Arthur; Taylor, M. Scott; Shalaby, Shalaby W.; Niklason, Laura E.

doi:10.1089/ten.tea.2010.0508

Cited by 34 publications

(34 citation statements)

References 33 publications

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“…Tissue engineered blood vessels derived from cell-sheet tissue engineering and degradable synthetic polymer scaffolding has demonstrated early clinical success and continued progress with several additional systems suggest that these technologies will continue to evolve [3, 6, 7]. We believe that clinical success will ultimately require utilizing a “bottom-up” approach where recapitulation of the fundamental features of the vascular wall, incorporation of key elements that obviate thrombosis and acute graft failure, and potentially the addition of a cellular component to provide a means for self-repair and other functional properties required for long-term graft patency [8–10].…”

Section: Introductionmentioning

confidence: 99%

Acellular vascular grafts generated from collagen and elastin analogs

Kumar¹,

Caves²,

Haller³

et al. 2013

Acta Biomaterialia

147

130

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Tissue engineered vascular grafts require long fabrication times, in part, due to the requirement of cells from a variety of cell sources to produce a robust load bearing, extracellular matrix. Herein, we propose a design strategy for the fabrication of tubular conduits comprised of collagen fiber networks and elastin-like protein polymers to mimic native tissue structure and function. Dense fibrillar collagen networks exhibited an ultimate tensile strength (UTS) of 0.71 ± 0.06 MPa, strain to failure of 37.1 ± 2.2%, and Young’s modulus of 2.09 ± 0.42 MPa, comparing favorably to an UTS and a Young’s modulus for native blood vessels of 1.4 – 11.1 MPa and 1.5 ± 0.3 MPa, respectively. Resilience, a measure of recovered energy during unloading of matrices, demonstrated that 58.9 ± 4.4% of the energy was recovered during loading-unloading cycles. Rapid fabrication of multilayer tubular conduits with maintenance of native collagen ultrastructure was achieved with internal diameters ranging between 1 to 4 mm. Compliance and burst pressures exceeded 2.7 ± 0.3%/100 mmHg and 830 ± 131 mmHg, respectively, with a significant reduction in observed platelet adherence as compared to ePTFE (6.8 ± 0.05 × 105 vs. 62 ± 0.05 × 105 platelets/mm2, p < 0.01). Using a rat aortic interposition model, early in vivo responses were evaluated at 2 weeks via Doppler ultrasound and CT angiography with immunohistochemistry confirming a limited early inflammatory response (n=8). Engineered collagen-elastin composites represent a promising strategy for fabricating synthetic tissues with defined extracellular matrix content, composition, and architecture.

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Section: Introductionmentioning

confidence: 99%

Acellular vascular grafts generated from collagen and elastin analogs

Kumar¹,

Caves²,

Haller³

et al. 2013

Acta Biomaterialia

147

130

View full text Add to dashboard Cite

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“…Tissue-engineered vascular grafts have been generated by seeding allogenic human primary VSMCs onto polyglycolic acid (PGA) scaffolds and culturing in bioreactors for 8–10 weeks [5, 13, 20, 33, 34]. Importantly, decellularization of vascular grafts can eliminate or greatly reduce cell-based immunogenicity and enable a longer-term storage, thus providing off-the-shelf product for current clinical trials [20, 35].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, other potential scaffold materials that may produce degradation products with minimal effect on VSMCs could be considered in future vessel engineering work. For example, it was reported that material composed of 87% glycolide, 7% trimethylene carbonate, and 6% polyethylene glycol degrades more extensively than PGA in the presence of VSMCs, leading to enhanced VSMC proliferation and collagen deposition[34]. Additionally, esterified hyaluronic acid, a material commonly used in vascular tissue engineering, was also reported to be degraded by newly formed tissue, and the degradation products appear to be readily biocompatible for VSMCs [40, 41].…”

Section: Discussionmentioning

confidence: 99%

Vascular smooth muscle cells derived from inbred swine induced pluripotent stem cells for vascular tissue engineering

et al. 2017

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Development of autologous tissue-engineered vascular constructs using vascular smooth muscle cells (VSMCs) derived from human induced pluripotent stem cells (iPSCs) holds great potential in treating patients with vascular disease. However, preclinical, large animal iPSC-based cellular and tissue models are required to evaluate safety and efficacy prior to clinical application. Herein, swine iPSC (siPSC) lines were established by introducing doxycycline-inducible reprogramming factors into fetal fibroblasts from a line of inbred Massachusetts General Hospital miniature swine that accept tissue and organ transplants without immunosuppression within the line. Highly enriched, functional VSMCs were derived from siPSCs based on addition of ascorbic acid and inactivation of reprogramming factor via doxycycline withdrawal. Moreover, siPSC-VSMCs seeded onto biodegradable polyglycolic acid (PGA) scaffolds readily formed vascular tissues, which were implanted subcutaneously into immunodeficient mice and showed further maturation revealed by expression of the mature VSMC marker, smooth muscle myosin heavy chain. Finally, using a robust cellular self-assembly approach, we developed 3D scaffold-free tissue rings from siPSC-VSMCs that showed comparable mechanical properties and contractile function to those developed from swine primary VSMCs. These engineered vascular constructs, prepared from doxycycline-inducible inbred siPSCs, offer new opportunities for preclinical investigation of autologous human iPSC-based vascular tissues for patient treatment.

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“…21 The united application of PLLA and PCL is based on the fact that one polymer is often not enough to meet all the requirements of prosthetic vascular grafts. 22 For example, the biocompatibility of PCL is poor owing to its hydrophobicity and lack of cellular specific interaction, 18 while PLLA has favorable biocompatibility. 19 Moreover, we have previously reported that electrospun P(LLA-CL) nanofibers were able to secure the adhesion and growth of ECs and SMCs; 15,16 this copolymer has also been suggested as an ideal material for vascular tissue engineering.…”

Section: Discussionmentioning

confidence: 99%

Fabrication of small-diameter vascular scaffolds by heparin-bonded P(LLA-CL) composite nanofibers to improve graft patency

Wang¹,

Mo²,

Jiang³

et al. 2013

IJN

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Abstract:The poor patency rate following small-diameter vascular grafting remains a major hurdle for the widespread clinical application of artificial blood vessels to date. Our previous studies found that electrospun poly(L-lactide-co-epsilon-caprolactone) (P[LLA-CL]) nanofibers facilitated the attachment and growth of endothelial cells (EC), and heparin incorporated into P(LLA-CL) nanofibers was able to release in a controlled manner. Hence, we hypothesized that heparin-bonded P(LLA-CL) vascular scaffolds with autologous EC pre-endothelialization could significantly promote the graft patency rate. To construct a small-diameter vascular scaffold, the inner layer was fabricated by heparin-bonded P(LLA-CL) nanofibers through coaxial electrospinning, while the outer layer was woven by pure P(LLA-CL) nanofibers. Except dynamic compliance (5.4 ± 1.7 versus 12.8 ± 2.4 × 10 −4 /mmHg, P , 0.05), maximal tensile strength, burst pressure, and suture retention of the composite, scaffolds were comparable to those of canine femoral arteries. In vitro studies indicated that the scaffolds can continuously release heparin for at least 12 weeks and obtain desirable endothelialization through dynamic incubation, which was confirmed by EC viability and proliferation assay and scanning electronic microscopy. Furthermore, in vivo studies demonstrated that pre-endothelialization by autologous ECs provided a better effect on graft patency rate in comparison with heparin loading, and the united application of pre-endothelialization and heparin loading markedly promoted the 24 weeks patency rate of P(LLA-CL) scaffolds (88.9% versus 12.5% in the control group, P , 0.05) in the canine femoral artery replacement model. These results suggest that heparin-bonded P(LLA-CL) scaffolds have similar biomechanical properties to those of native arteries and possess a multiporous and biocompatible surface to achieve satisfactory endothelialization in vitro. Heparin-bonded P(LLA-CL) scaffolds with autologous EC pre-endothelialization have the potential to be substitutes for natural small-diameter vessels in planned vascular bypass surgery.

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Development of Novel Biodegradable Polymer Scaffolds for Vascular Tissue Engineering

Cited by 34 publications

References 33 publications

Acellular vascular grafts generated from collagen and elastin analogs

Acellular vascular grafts generated from collagen and elastin analogs

Vascular smooth muscle cells derived from inbred swine induced pluripotent stem cells for vascular tissue engineering

Fabrication of small-diameter vascular scaffolds by heparin-bonded P(LLA-CL) composite nanofibers to improve graft patency

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