The effect of pore diameter on neo-tissue formation in electrospun biodegradable tissue-engineered arterial grafts in a large animal model

Matsuzaki, Yuichi; Iwaki, Ryuma; Reinhardt, James W.; Chang, Yu-Chun; Miyamoto, Shinka; Kelly, John; Zbinden, Jacob; Blum, Kevin M.; Mirhaidari, Gabriel; Ulziibayar, Anudari; Shoji, Tetsuo; Breuer, Christopher K.; Shinoka, Toshiharu

doi:10.1016/j.actbio.2020.08.011

Cited by 38 publications

(27 citation statements)

References 26 publications

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“…Heparin functionalization of synthetic small‐diameter TEVGs is an often‐reported strategy to prevent thrombus formation. [ 45–54 ] Surprisingly, we did not observe a clear reduction in platelet activation in the hep group when compared to bare group (Figure S3, Supporting Information). This observation, in case of heparin functionalized groups (either with or without IL‐4), is in apparent contrast with the canonical definition of heparin as a potent anticoagulant.…”

Section: Discussionmentioning

confidence: 82%

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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Section: Discussionmentioning

confidence: 82%

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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“…The copyright holder for this preprint (which this version posted April 8, 2021. ; https://doi.org/10.1101/2021.04.06.438611 doi: bioRxiv preprint Pore size is one of the design parameters known to influence cell infiltration, fibroblast activation as well as macrophage polarization [45]- [47]. Moreover, Wissing et al…”

Section: Discussionmentioning

confidence: 99%

“…Pore size is one of the design parameters known to influence cell infiltration, fibroblast activation as well as macrophage polarization [45]- [47]. Moreover, Wissing et al…”

Section: Discussionmentioning

confidence: 99%

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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“…In other studies, TIPS was also combined with electrospinning, for instance, to generate a bilayer scaffold by electrospinning a synthetic polymer onto the outer surface of the TIPS-produced sponge inner layer [ 103 ]. However, in their electrospinning process, the produced grafts were unable to resist dilation by high pressures.…”

Section: Combination Of Solution-based Techniquesmentioning

confidence: 99%

Solution-Based Processing for Scaffold Fabrication in Tissue Engineering Applications: A Brief Review

et al. 2021

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The fabrication of 3D scaffolds is under wide investigation in tissue engineering (TE) because of its incessant development of new advanced technologies and the improvement of traditional processes. Currently, scientific and clinical research focuses on scaffold characterization to restore the function of missing or damaged tissues. A key for suitable scaffold production is the guarantee of an interconnected porous structure that allows the cells to grow as in native tissue. The fabrication techniques should meet the appropriate requirements, including feasible reproducibility and time- and cost-effective assets. This is necessary for easy processability, which is associated with the large range of biomaterials supporting the use of fabrication technologies. This paper presents a review of scaffold fabrication methods starting from polymer solutions that provide highly porous structures under controlled process parameters. In this review, general information of solution-based technologies, including freeze-drying, thermally or diffusion induced phase separation (TIPS or DIPS), and electrospinning, are presented, along with an overview of their technological strategies and applications. Furthermore, the differences in the fabricated constructs in terms of pore size and distribution, porosity, morphology, and mechanical and biological properties, are clarified and critically reviewed. Then, the combination of these techniques for obtaining scaffolds is described, offering the advantages of mimicking the unique architecture of tissues and organs that are intrinsically difficult to design.

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The effect of pore diameter on neo-tissue formation in electrospun biodegradable tissue-engineered arterial grafts in a large animal model

Cited by 38 publications

References 26 publications

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

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

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

Solution-Based Processing for Scaffold Fabrication in Tissue Engineering Applications: A Brief Review

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