Isolated effect of material stiffness on valvular interstitial cell differentiation

Coombs, Kent E.; Leonard, Alexander T.; Rush, Matthew N.; Santistevan, David A.; Hedberg-Dirk, Elizabeth L.

doi:10.1002/jbm.a.35864

Cited by 10 publications

(6 citation statements)

References 42 publications

(195 reference statements)

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“…Calcification is a main factor reported to occur with long use of implants and consequently cause failure. Calcific degeneration remains a major obstacle facing the translation of tissue‐engineered vascular grafts for arterial repair . Thus, calcification degree is an important indicator to evaluate the success of the implanted material.…”

Section: Discussionmentioning

confidence: 99%

The regeneration of macro‐porous electrospun poly(ɛ‐caprolactone) vascular graft during long‐termin situimplantation

Qin

Wang

et al. 2017

J Biomed Mater Res

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Long-term evaluation of vascular grafts is an essential step to facilitate clinical translation. In this study, we investigate the long-term performance of a macro-porous poly(ɛ-caprolactone) (PCL) electrospun vascular graft using the rat abdominal artery replacement model. Long-term patency, endothelialization, and smooth muscle cell regeneration were evaluated, as well as calcification and degradation. The data showed that all the grafts remained open and unobstructed. There was no evidence of aneurysm, stenosis, or calcification one year after implantation. Importantly, neo-vessel was regenerated on the luminal surface of the graft, and was composed of a complete endothelial layer and several layers of smooth muscle cells. The neo-vessel showed vascular physiological function, although not as good as that in native blood vessels, likely due to the remaining scaffold fibers. These data indicated that the PCL macro-porous electrospun vascular graft has potential to be an artery substitute for long-term implantation. Also, this work indicates that continued efforts are needed to develop advanced vascular grafts that exhibit the appropriate balance between the regeneration of the neo-vessel and the complete degradation of the graft materials. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1618-1627, 2018.

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Section: Discussionmentioning

confidence: 99%

The regeneration of macro‐porous electrospun poly(ɛ‐caprolactone) vascular graft during long‐termin situimplantation

Qin

Wang

et al. 2017

J Biomed Mater Res

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“…A collagen gel is reminiscent of ECM conditions in that collagen is one of the representative proteins existent in vivo . However, some synthetic polymers like a co-polymer system of n-octyl methacrylate crosslinked with diethylene glycol dimethacrylate (DEGDMA/nOM) prove ideal for differentiation studies looking for independent effects of substrate stiffness without the inconsistency of surface chemistry [94]. This co-polymer system elucidated the mechanosensitivity of cells to their substrates by revealing that after a certain stiffness threshold, gene expression does not increase but rather re-organizes corresponding to the formation of osteoblastic markers which are known to associate with higher stiffness.…”

Section: Biophysical Regulation Of Cell Reprogrammingmentioning

confidence: 99%

“…Overall, no matter the amount of mechanical loading, hMSCs will lose their stemness and gain the factors towards osteoblastic or tendon/ligament differentiation [98, 101]. The cell orientation will convert to a direction perpendicular to stress orientation, providing a tissue response that seeks to balance the stress it is exposed to [94]. For example, a recent study developed a probe to investigate cell actin stress and its role in cell reprogramming and differentiation, which could elucidate how cellular mechanics can influence cell fate [103].…”

Section: Biophysical Regulation Of Cell Reprogrammingmentioning

confidence: 99%

A biomaterial approach to cell reprogramming and differentiation

Long

Kim

et al. 2017

J. Mater. Chem. B

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Cell reprogramming of somatic cells into pluripotent states and subsequent differentiation into certain phenotypes has helped progress regenerative medicine research and other medical applications. Recent research has used viral vectors to induce this reprogramming; however, limitations include low efficiency and safety concerns. In this review, we discuss how biomaterial methods offer potential avenues for either increasing viability and downstream applicability of viral methods, or providing a safer alternative. The use of non-viral delivery systems, such as electroporation, micro/nanoparticles, nucleic acids and the modulation of culture substrate topography and stiffness have generated valuable insights regarding cell reprogramming.

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“…The phenotype of valvular interstitial cells (VICs), the most abundant and plastic cell population in the valve, can be modulated by the properties of cell culture substrate/matrix . It has been revealed that matrix stiffness affects the activation and osteogenic differentiation of VICs . Moreover, the morphology and architecture of valvular ECM have been shown to instruct the attachment and spreading of VICs .…”

Section: Introductionmentioning

confidence: 99%

“…6,7 It has been revealed that matrix stiffness affects the activation and osteogenic differentiation of VICs. [8][9][10] Moreover, the morphology and architecture of valvular ECM have been shown to instruct the attachment and spreading of VICs. 11,12 Several studies have performed uniaxial tensile testing on tissue-engineered scaffolds, 13,14 but uniaxial testing is insufficient to fully characterize the scaffold mechanical properties as it fails to capture the complex cross-coupling (stress along one axis is affected by the strain level along the perpendicular axis) experienced by the anisotropic tissues.…”

mentioning

confidence: 99%

Valve leaflet‐inspired elastomeric scaffolds with tunable and anisotropic mechanical properties

Xue

Ravishankar

Zeballos

et al. 2019

Polymers for Advanced Techs

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Fibrous scaffolds, which can mimic the elastic and anisotropic mechanical properties of native tissues, hold great promise in recapitulating the native tissue microenvironment. We previously fabricated electrospun fibrous scaffolds made of hybrid synthetic elastomers (poly(1,3‐diamino‐2‐hydroxypropane‐co‐glycerol sebacate)‐co‐poly (ethylene glycol) (APS‐co‐PEG) and polycaprolactone (PCL)) to obtain uniaxial mechanical properties similar to those of human aortic valve leaflets. However, conventional electrospinning process often yields scaffolds with random alignment, which fails to recreate the anisotropic nature of most of the soft tissues such as native heart valves. Inspired by the structure of native valve leaflet, we designed a novel valve leaflet‐inspired ring‐shaped collector to modulate the electrospun fiber alignment and studied the effect of polymer formulation (PEG amount [mole %] in APS‐co‐PEG; ratio between APS‐co‐PEG and PCL; and total polymer concentration) in tuning the biaxial mechanical properties of the fibrous scaffolds. The fibrous scaffolds collected on the ring‐shaped collector displayed anisotropic biaxial mechanical properties, suggesting that their biaxial mechanical properties are closely associated with the fiber alignment in the scaffold. Additionally, the scaffold stiffness was easily tuned by changing the composition and concentration of the polymer blend. Human valvular interstitial cells (hVICs) cultured on these anisotropic scaffolds displayed aligned morphology as instructed by the fiber alignment. Overall, we generated a library of biologically relevant fibrous scaffolds with tunable mechanical properties, which will guide the cellular alignment.

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Isolated effect of material stiffness on valvular interstitial cell differentiation

Cited by 10 publications

References 42 publications

The regeneration of macro‐porous electrospun poly(ɛ‐caprolactone) vascular graft during long‐termin situimplantation

The regeneration of macro‐porous electrospun poly(ɛ‐caprolactone) vascular graft during long‐termin situimplantation

A biomaterial approach to cell reprogramming and differentiation

Valve leaflet‐inspired elastomeric scaffolds with tunable and anisotropic mechanical properties

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