Transcatheter-Delivered Expandable Bioresorbable Polymeric Graft With Stenting Capacity Induces Vascular Regeneration

Duijvelshoff, Renée; Cabrera, Maria; Sanders, Bart; Dekker, Sylvia; Smits, Anthal I.P.M.; Baaijens, Fpt Frank; Bouten, Cvc Carlijn

doi:10.1016/j.jacbts.2020.09.005

Cited by 11 publications

(6 citation statements)

References 52 publications

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“…This may also explain why elastic fiber assembly was only detected at late time points, at which the inflammatory environment had locally resolved in graft-free regions. The latter was recently reported by Duijvelshoff et al, who demonstrated a trend of mature elastic fiber regeneration in resorbable synthetic endovascular stents in pace with a reduction in macrophage presence [58]. Overall, the present findings regarding tissue formation and maturation suggest that scaffold resorption of in situ TEHVs should be relatively slow in order to allow for sufficient mature and functional tissue formation prior to full scaffold resorption.…”

Section: Discussionsupporting

confidence: 83%

Inflammatory and regenerative processes in bioresorbable synthetic pulmonary valves up to 2 years in sheep: Spatiotemporal insights augmented by Raman microspectroscopy

Kort

Marzi

Brauchle³

et al. 2021

Preprint

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In situ heart valve tissue engineering is an emerging approach in which resorbable, off-the-shelf porous polymeric scaffolds containing leaflets and conduit are used to induce endogenous heart valve restoration. Such scaffolds are designed to recruit endogenous cells in vivo, which subsequently resorb polymer and produce and remodel new valvular tissue in situ. Recently, preclinical studies using electrospun supramolecular elastomeric valvular grafts have shown that this approach enables in situ regeneration of pulmonary valves with long-term functionality in vivo. However, the evolution and mechanisms of inflammation, polymer absorption and tissue regeneration are largely unknown, and adverse valve remodeling and intra- and inter-valvular variability have been reported. Therefore, the goal of the present study was to gain a mechanistic understanding of the in vivo regenerative processes by combining routine histology and immunohistochemistry, using a comprehensive sheep-specific antibody panel, with Raman microspectroscopy for the spatiotemporal analysis of in situ tissue-engineered pulmonary valves with follow-up to 24 months from a previous preclinical study in sheep. The analyses revealed a strong spatial heterogeneity in the influx of inflammatory cells, graft resorption, and foreign body giant cells. Collagen maturation occurred predominantly between 6 and 12 months after implantation, which was accompanied by a progressive switch to a more quiescent phenotype of infiltrating cells with properties of valvular interstitial cells. Variability among specimens in the extent of tissue remodeling was observed for follow-up times after 6 months. Taken together, these findings advance the understanding of key events and mechanisms in material-driven in situ heart valve tissue engineering.

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Section: Discussionsupporting

confidence: 83%

Inflammatory and regenerative processes in bioresorbable synthetic pulmonary valves up to 2 years in sheep: Spatiotemporal insights augmented by Raman microspectroscopy

Kort

Marzi

Brauchle³

et al. 2021

Preprint

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“…Collagen I was abundantly distributed throughout the graft area (from the lumen to the adventitial layer), whereas collagen III expression was minimal. This may be the result of collagen III gradually shifting to collagen I during maturation, as seen in previous studies [15,20]. The wall thicknesses of native vessels and PCL/PDO grafts were 296 ± 10 and 618 ± 87 μm, respectively (p = 0.014; Fig.…”

Section: Results Of Immunohistological Stainingsupporting

confidence: 75%

“…CD68-positive cells (macrophages) were observed in the PCL/PDO grafts (Fig. 5 A, first panel), but were mainly localized in the graft remnants (tunica media and adventitia; yellow arrow) at low density, suggesting a minimal inflammatory response and active polymer resorption [ 20 ]. This result is consistent with previous findings of a considerable reduction in the number of CD68-positive cells at 4 months after implantation [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

Rapid remodeling observed at mid-term in-vivo study of a smart reinforced acellular vascular graft implanted on a rat model

et al. 2023

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Background The poor performance of conventional techniques used in cardiovascular disease patients requiring hemodialysis or arterial bypass grafting has prompted tissue engineers to search for clinically appropriate off-the-shelf vascular grafts. Most patients with cardiovascular disease lack suitable autologous tissue because of age or previous surgery. Commercially available vascular grafts with diameters of < 5 mm often fail because of thrombosis and intimal hyperplasia. Result Here, we tested tubular biodegradable poly-e-caprolactone/polydioxanone (PCL/PDO) electrospun vascular grafts in a rat model of aortic interposition for up to 12 weeks. The grafts demonstrated excellent patency (100%) confirmed by Doppler Ultrasound, resisted aneurysmal dilation and intimal hyperplasia, and yielded neoarteries largely free of foreign materials. At 12 weeks, the grafts resembled native arteries with confluent endothelium, synchronous pulsation, a contractile smooth muscle layer, and co-expression of various extracellular matrix components (elastin, collagen, and glycosaminoglycan). Conclusions The structural and functional properties comparable to native vessels observed in the neoartery indicate their potential application as an alternative for the replacement of damaged small-diameter grafts. This synthetic off-the-shelf device may be suitable for patients without autologous vessels. However, for clinical application of these grafts, long-term studies (> 1.5 years) in large animals with a vasculature similar to humans are needed.

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“…This is in line with recent findings by Duijvelshoff et al., who demonstrated a progressive regeneration of mature elastic fibers accompanied by a progressive decrease in macrophage presence in regenerative resorbable synthetic stents. [ 67 ] It is plausible that the early pro‐regenerative environment induced by IL‐4 contributes to a more favorable biochemical milieu for elastin accumulation, for example by limiting the secretion of elastase by pro‐inflammatory macrophages. [ 68 ]…”

Section: Discussionmentioning

confidence: 99%

Distinct Effects of Heparin and Interleukin‐4 Functionalization on Macrophage Polarization and In Situ Arterial Tissue Regeneration Using Resorbable Supramolecular Vascular Grafts in Rats

Bonito

Koch

Krebber

et al. 2021

Adv Healthcare Materials

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Two of the greatest challenges for successful application of small‐diameter in situ tissue‐engineered vascular grafts are 1) preventing thrombus formation and 2) harnessing the inflammatory response to the graft to guide functional tissue regeneration. This study evaluates the in vivo performance of electrospun resorbable elastomeric vascular grafts, dual‐functionalized with anti‐thrombogenic heparin (hep) and anti‐inflammatory interleukin 4 (IL‐4) using a supramolecular approach. The regenerative capacity of IL‐4/hep, hep‐only, and bare grafts is investigated as interposition graft in the rat abdominal aorta, with follow‐up at key timepoints in the healing cascade (1, 3, 7 days, and 3 months). Routine analyses are augmented with Raman microspectroscopy, in order to acquire the local molecular fingerprints of the resorbing scaffold and developing tissue. Thrombosis is found not to be a confounding factor in any of the groups. Hep‐only‐functionalized grafts resulted in adverse tissue remodeling, with cases of local intimal hyperplasia. This is negated with the addition of IL‐4, which promoted M2 macrophage polarization and more mature neotissue formation. This study shows that with bioactive functionalization, the early inflammatory response can be modulated and affect the composition of neotissue. Nevertheless, variability between graft outcomes is observed within each group, warranting further evaluation in light of clinical translation.

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Transcatheter-Delivered Expandable Bioresorbable Polymeric Graft With Stenting Capacity Induces Vascular Regeneration

Abstract: Visual Abstract

Cited by 11 publications

References 52 publications

Inflammatory and regenerative processes in bioresorbable synthetic pulmonary valves up to 2 years in sheep: Spatiotemporal insights augmented by Raman microspectroscopy

Inflammatory and regenerative processes in bioresorbable synthetic pulmonary valves up to 2 years in sheep: Spatiotemporal insights augmented by Raman microspectroscopy

Rapid remodeling observed at mid-term in-vivo study of a smart reinforced acellular vascular graft implanted on a rat model

Distinct Effects of Heparin and Interleukin‐4 Functionalization on Macrophage Polarization and In Situ Arterial Tissue Regeneration Using Resorbable Supramolecular Vascular Grafts in Rats

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