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Large strain stimulation promotes extracellular matrix production and stiffness in an elastomeric scaffold model

Affiliations

  • 1 Department of Bioengineering McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Fondazione RiMED, Italy; DICGIM, Università di Palermo, Italy.
  • 2 Center for Cardiovascular Simulation, Institute for Computational Engineering and Sciences, Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.
  • 3 Department of Bioengineering McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
  • 4 Department of Cardiac Surgery Boston Children׳s Hospital and Harvard Medical School, Boston, MA, USA.
  • 5 Center for Cardiovascular Simulation, Institute for Computational Engineering and Sciences, Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA. Electronic address: [email protected]
  • PMID: 27344402
  • PMCID: PMC4955736
  • DOI: 10.1016/j.jmbbm.2016.05.005

Free PMC article

Large strain stimulation promotes extracellular matrix production and stiffness in an elastomeric scaffold model

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Authors

Affiliations

  • 1 Department of Bioengineering McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Fondazione RiMED, Italy; DICGIM, Università di Palermo, Italy.
  • 2 Center for Cardiovascular Simulation, Institute for Computational Engineering and Sciences, Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.
  • 3 Department of Bioengineering McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
  • 4 Department of Cardiac Surgery Boston Children׳s Hospital and Harvard Medical School, Boston, MA, USA.
  • 5 Center for Cardiovascular Simulation, Institute for Computational Engineering and Sciences, Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA. Electronic address: [email protected]
  • PMID: 27344402
  • PMCID: PMC4955736
  • DOI: 10.1016/j.jmbbm.2016.05.005

Abstract

Mechanical conditioning of engineered tissue constructs is widely recognized as one of the most relevant methods to enhance tissue accretion and microstructure, leading to improved mechanical behaviors. The understanding of the underlying mechanisms remains rather limited, restricting the development of in silico models of these phenomena, and the translation of engineered tissues into clinical application. In the present study, we examined the role of large strip-biaxial strains (up to 50%) on ECM synthesis by vascular smooth muscle cells (VSMCs) micro-integrated into electrospun polyester urethane urea (PEUU) constructs over the course of 3 weeks. Experimental results indicated that VSMC biosynthetic behavior was quite sensitive to tissue strain maximum level, and that collagen was the primary ECM component synthesized. Moreover, we found that while a 30% peak strain level achieved maximum ECM synthesis rate, further increases in strain level lead to a reduction in ECM biosynthesis. Subsequent mechanical analysis of the formed collagen fiber network was performed by removing the scaffold mechanical responses using a strain-energy based approach, showing that the denovo collagen also demonstrated mechanical behaviors substantially better than previously obtained with small strain training and comparable to mature collagenous tissues. We conclude that the application of large deformations can play a critical role not only in the quantity of ECM synthesis (i.e. the rate of mass production), but also on the modulation of the stiffness of the newly formed ECM constituents. The improved understanding of the process of growth and development of ECM in these mechano-sensitive cell-scaffold systems will lead to more rational design and manufacturing of engineered tissues operating under highly demanding mechanical environments.

Keywords: ECM (extracellular matrix); Elastomeric scaffold; Mechanical conditioning; Mechanical properties.

Copyright © 2016 Elsevier Ltd. All rights reserved.

Figures

A) Electrospinning device utilized in…

A) Electrospinning device utilized in the study with related fabrication variables. B) sample…

A) Stretch bioreactor loaded with…

A) Stretch bioreactor loaded with specimen rings under uniaxial tension, conditioning regimen variables…

A) Sample elongation and B)…

A) Sample elongation and B) volume changes for different strain levels and time…

A) H&E and B) picrosirius…

A) H&E and B) picrosirius red staining of specimens conditioned for 14 days…

A) Collagen and B) GAG…

A) Collagen and B) GAG synthesis as a function of finite deformation stimulation…

Polymer and ECM components for…

Polymer and ECM components for 21 day samples before and after the ECM…

Mechanical effects of trypsin degradation…

Mechanical effects of trypsin degradation on the PEUU component A) seven protocol tests…

Evaluation of the mechanical response…

Evaluation of the mechanical response of the de novo ECM: A) seven protocol…

Stored energy density under equi-strain…

Stored energy density under equi-strain conditions of the response of the average engineered…

Mechanical conditioning of engineered tissue constructs is widely recognized as one of the most relevant methods to enhance tissue accretion and microstructure, leading to improved mechanical behaviors. The understanding of the underlying mechanisms remains rather limited, restricting the developmen …

strain amore

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Product Review: Sensi Chews Amoré Medicated Chocolate

I met some folks from Sensi at a Women Grow event in LA and was instantly curious. An aphrodisiac chocolate chew? Would it make me feel aroused, or just less stressed? Would it increase sensation or reduce inhibitions? Here’s the lowdown.

Amoré Medicated Chocolate at a Glance

Manufacturer: Sensi Chew

Ingredients: Sugar, corn syrup, butter, cream, cocoa, vanilla, Tongkat Ali extract, cannabis extract

Cannabis content: 25mg THC per chew (two chews per package)

Available in: California

Initial Impressions

Pros:

  • I appreciate that the package is resealable. The label doubles as a press-and-seal so if you don’t want to do the full 25 milligrams, you can bite one of the chews in half and save the other half for another time.
  • It tastes really yummy, though I don’t get as much of the caramel taste; the chocolate is more noticeable. There isn’t a strong cannabis taste, either. The consistency is like fudge; it reminds me of a less chewy version of a Tootsie roll.
  • As I felt the effects begin, I could feel a bit of spaceyness behind my eyes. I felt emotionally open and communicative but not unpleasantly chatty. I was able to discern a difference in body sensation after the chew took effect.
  • The high is mellow and balanced. I felt my entire body relax and come online in a pleasant way. I asked my friend to touch my arm and he sort of patted it, and I grinned and said, “no, sexy touching,” and he started dragging his fingertips lightly over my forearm. I felt a difference with the second type of touch. It was intentional and it evoked a stronger reaction in my body, notably enhanced by the Amoré chew.
  • The other active ingredient, aside from cannabis, is Tongkat Ali. This flowering plant from Indonesia has been studied as a natural testosterone booster. I had no way to test my testosterone levels, but I did feel more touch-oriented and magnetized after I enjoyed the Amoré square.
  • I tried the other chew at a different time to test it out for solo play and I found that it helped me relax and enjoy the experience of pleasure rather than getting caught up in how long it was taking me to get to a specific destination. I didn’t feel like it specifically decreased inhibitions (not that I have a ton anyway) but I definitely felt less stressed and more balanced.

Cons:

  • The packaging feels flimsy and a bit dated. I showed it to my friend Arden and she said, “it looks like something you’d see at a gas station on a shelf next to bottles of Horny Goat Weed.” Perhaps sharper than I would have gone, but she has a point. I also found myself a bit confused – if it works on all bodies (as indicated by the “for him and her” designation on the label) then why does the packaging need to feature a man and woman kissing? I’d love to see more forward-thinking packaging that reflects the quality of the product inside of it.
  • The dosage is potentially too high for new users. I typically suggest that a newbie start with 2.5mg to 5mg total, which would be difficult to manage with this product since it comes in two individual doses of 25mg each.
  • As with any edible product, the onset time and duration will be largely dependent on your metabolism and tolerance. I started to feel the effects after about 50 minutes and noticeable effects lasted for about an hour and a half to two hours. The package suggests that it could last up to six hours, which is entirely possible depending on your specific reaction to the amount of THC you ingest. Dose yourself accordingly.

Our Verdict

I enjoyed this product. I could imagine bringing a two-pack of chews and going on a weekend adventure with a lover, planning to fill at least one of the days with nothing but sensual delights. Have you tried the Amore Sensi Chews? What did you think?

Our review of Sensi Chew’s Amoré Aphrodisiac Medicated Chocolate Caramel, available in California, considers pros and cons before offering a verdict on whether it’s worth buying.

Product Review: Sensi Chews Amoré Medicated Chocolate I met some folks from Sensi at a Women Grow event in LA and was instantly curious. An aphrodisiac