Rapid Endothelialization of Off-the-Shelf Small Diameter Silk Vascular Grafts

Filipe, Elysse C.; Santos, Miguel; Hung, Juichien; Lee, Bob S.L.; Yang, Nianji; Chan, Alex; Ng, M.; Rnjak‐Kovacina, Jelena; Wise, Steven G.

doi:10.1016/j.jacbts.2017.12.003

Cited by 60 publications

(52 citation statements)

References 42 publications

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“…The relative contribution of each secondary structure was determined by integration of the corresponding fitted peaks obtained from FSD calculations. The position of each peak was further confirmed by double differentiation of the amide I envelopes and peak assignment was as follow: side chains (1595–1605 cm −1 ); β‐sheets (1610–1628 and 1697–1704 cm −1 ); random coils (1635–1650 cm −1 ); alpha‐helix (1652–1660 cm −1 ), and beta‐turns (1663–1695 cm −1 ). A nonlinear least‐square convergence criterion monitored the error between the original and deconvoluted spectra, imposing relative errors below 10 −6 .…”

Section: Methodsmentioning

confidence: 95%

Rapid Photocrosslinking of Silk Hydrogels with High Cell Density and Enhanced Shape Fidelity

Cui

Soliman

Alcala-Orozco

et al. 2020

Adv Healthcare Materials

Self Cite

121

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Silk fibroin hydrogels crosslinked through di‐tyrosine bonds are clear, elastomeric constructs with immense potential in regenerative medicine applications. In this study, demonstrated is a new visible light‐mediated photoredox system for di‐tyrosine bond formation in silk fibroin that overcomes major limitations of current conventional enzymatic‐based crosslinking. This photomediated system rapidly crosslinks silk fibroin (<1 min), allowing encapsulation of cells at significantly higher cell densities (15 million cells mL−1) while retaining high cell viability (>80%). The photocrosslinked silk hydrogels present more stable mechanical properties which do not undergo spontaneous transition to stiff, β‐sheet‐rich networks typically seen for enzymatically crosslinked systems. These hydrogels also support long‐term culture of human articular chondrocytes, with excellent cartilage tissue formation. This system also facilitates the first demonstration of biofabrication of silk fibroin constructs in the absence of chemical modification of the protein structure or rheological additives. Cell‐laden constructs with complex, ordered, graduated architectures, and high resolution (40 µm) are fabricated using the photocrosslinking system, which cannot be achieved using the enzymatic crosslinking system. Taken together, this work demonstrates the immense potential of a new crosslinking approach for fabrication of elastomeric silk hydrogels with applications in biofabrication and tissue regeneration.

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Section: Methodsmentioning

confidence: 95%

Rapid Photocrosslinking of Silk Hydrogels with High Cell Density and Enhanced Shape Fidelity

Cui

Soliman

Alcala-Orozco

et al. 2020

Adv Healthcare Materials

Self Cite

121

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“…In this study, we demonstrate that changing the silk manufacturing process and therefore altering the fibre thickness and porosity of electrospun silk vascular grafts has a profound effect on vascular remodelling in a rat abdominal aorta grafting model. Compared to a water spun (WS) silk graft with relatively low porosity previously developed in our lab 13 , we observed significantly more rapid re-endothelisation on a HFIP spun (HS) silk graft spun with increased fibre diameter and higher porosity. Maturation of neointimal hyperplasia was also accelerated, plateauing at earlier timepoints compared to low porosity grafts and characterised by enhanced deposition of extracellular matrix proteins.…”

Section: Introductioncontrasting

confidence: 52%

“…While several methods of graft generation are compatible with silk, electrospinning has some intrinsic advantages, with multiple studies demonstrating modulation of fibre diameter 8 , mechanical properties 9,10 and blending with other synthetic polymers or proteins to obtain hybrid scaffolds 11,12 . Following several studies exploring the feasibility of making durable synthetic silk conduits, recent advances in silk processing have made mechanically robust conduits feasible for the first time 13 . While physical scaffold parameters such as elasticity, fibre diameter and porosity are known to influence cell infiltration, morphology and signalling in flat scaffolds, the effect of these parameters on long-term graft performance is less clear.…”

Section: Introductionmentioning

confidence: 99%

Altered processing enhances the efficacy of small-diameter silk fibroin vascular grafts

Chan

Filipe

Tan

et al. 2019

Sci Rep

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Current synthetic vascular grafts are not suitable for use in low-diameter applications. Silk fibroin is a promising natural graft material which may be an effective alternative. In this study, we compared two electrospun silk grafts with different manufacturing processes, using either water or hexafluoroisopropanol (HFIP) as solvent. This resulted in markedly different Young’s modulus, ultimate tensile strength and burst pressure, with HFIP spun grafts observed to have thicker fibres, and greater stiffness and strength relative to water spun. Assessment in a rat abdominal aorta grafting model showed significantly faster endothelialisation of the HFIP spun graft relative to water spun. Neointimal hyperplasia in the HFIP graft also stabilised significantly earlier, correlated with an earlier SMC phenotype switch from synthetic to contractile, increasing extracellular matrix protein density. An initial examination of the macrophage response showed that HFIP spun conduits promoted an anti-inflammatory M2 phenotype at early timepoints while reducing the pro-inflammatory M1 phenotype relative to water spun grafts. These observations demonstrate the important role of the manufacturing process and physical graft properties in determining the physiological response. Our study is the first to comprehensively study these differences for silk in a long-term rodent model.

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“…[ 25 ] Electrospun scaffolds composed of synthetic polymers have higher mechanical durability in terms of burst strength and compliance, though the use of naturally based polymers significantly improves cell engraftment. [ 26 ]…”

Section: Tissue Engineered Vascular Graftsmentioning

confidence: 99%

From Arteries to Capillaries: Approaches to Engineering Human Vasculature

Fleischer

Tavakol

Vunjak-Novakovic

2020

Adv Funct Materials

111

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From microscaled capillaries to millimeter‐sized vessels, human vasculature spans multiple scales and cell types. The convergence of bioengineering, materials science, and stem cell biology has enabled tissue engineers to recreate the structure and function of different hierarchical levels of the vascular tree. Engineering large‐scale vessels aims to replace damaged arteries, arterioles, and venules and their routine application in the clinic may become a reality in the near future. Strategies to engineer meso‐ and microvasculature are extensively explored to generate models for studying vascular biology, drug transport, and disease progression as well as for vascularizing engineered tissues for regenerative medicine. However, bioengineering tissues for transplantation has failed to result in clinical translation due to the lack of proper integrated vasculature for effective oxygen and nutrient delivery. The development of strategies to generate multiscale vascular networks and their direct anastomosis to host vasculature would greatly benefit this formidable goal. In this review, design considerations and technologies for engineering millimeter‐, meso‐, and microscale vessels are discussed. Examples of recent state‐of‐the‐art strategies to engineer multiscale vasculature are also provided. Finally, key challenges limiting the translation of vascularized tissues are identified and perspectives on future directions for exploration are presented.

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Rapid Endothelialization of Off-the-Shelf Small Diameter Silk Vascular Grafts

Cited by 60 publications

References 42 publications

Rapid Photocrosslinking of Silk Hydrogels with High Cell Density and Enhanced Shape Fidelity

Rapid Photocrosslinking of Silk Hydrogels with High Cell Density and Enhanced Shape Fidelity

Altered processing enhances the efficacy of small-diameter silk fibroin vascular grafts

From Arteries to Capillaries: Approaches to Engineering Human Vasculature

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