Cyclic strain increases fibroblast proliferation, matrix accumulation, and elastic modulus of fibroblast-seeded polyurethane constructs

Webb, K. E.; Hitchcock, Robert W.; Smeal, Roy M.; Li, Wenhua; Gray, Steven D.; Tresco, Patrick A.

doi:10.1016/j.jbiomech.2004.08.026

Cited by 137 publications

(116 citation statements)

References 48 publications

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“…This has led tissue engineers to include mechanical stimulation in their construct formation protocols. [23][24][25][26][27][28][29][30][31][32][33] However, there is little data that elucidates how mechanical forces change the dynamics of fibroblast populations in cell culture systems. This is because most investigations are performed by examining the culture at fixed time points either during or after the mechanical stimulation protocol is complete.…”

Section: Introductionmentioning

confidence: 99%

Design and Performance of an Optically Accessible, Low-Volume, Mechanobioreactor for Long-Term Study of Living Constructs

Paten

Zareian

Saeidi

et al. 2011

Tissue Engineering Part C: Methods

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Currently available bioreactor systems used by tissue engineers permit either direct, high-magnification observation of cell behavior or application of mechanical loads to growing tissue constructs, but not both simultaneously. Further, in most loading bioreactors, the volume of the dead space is not minimized to reduce the cost associated with perfusion media, exogenous stimulatory/inhibitory agents, proteases, and label. We have designed, developed, and tested a bioreactor that simultaneously satisfies the combined requirements of providing (i) controlled tensile mechanical stimulation, (ii) direct high-magnification imaging capability, and (iii) low dead-space volume. This novel mechanostimulatory (uniaxial tensile loading) bioreactor operates on an inverted microscope and permits continuous optical access (up to 600 · ) to a loaded, growing construct for extended periods of time (weeks). The reactor employs an adjustable reaction chamber in which the dead space can be reduced to < 2 mL. The device has been used to cultivate our human primary corneal fibroblastderived, tissue-engineered system for up to 14 days. Using the instrument we have successfully recorded (i) the process of fibroblasts populating, growing to confluence, and stratifying on different substrates; (ii) recorded complex and organized cell sheet motions; and (iii) recorded the behavior of a subpopulation of what appear to be degradative/catabolic cells within our fibroblast culture. The device is capable of providing detailed, long-term, dynamic images of mechanically stimulated cell/matrix interaction that have not been observed previously.

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Section: Introductionmentioning

confidence: 99%

Design and Performance of an Optically Accessible, Low-Volume, Mechanobioreactor for Long-Term Study of Living Constructs

Paten

Zareian

Saeidi

et al. 2011

Tissue Engineering Part C: Methods

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“…Pneumatic actuators, [19][20][21] linear motors, 22,27 and step motorball screws (SMBSs) 2,42,76 are the most common actuators used in tendon/ligament bioreactors. Pneumatic actuators have several advantages, including the ease of maintenance, cleanliness, low cost, and high power-to-weight ratio.…”

Section: Actuator and Culture Chamber Designmentioning

confidence: 99%

“…In a multichamber-shared loading system, SMBS is widely used given its high accuracy and relative high loading capacity. 35,42,76 In independent loading multichamber systems, linear motors are more popular due to their small size and relatively simple mechanical arrangement. 22,82 In the addition to the actuator, the connection between the mechanical input and the tissue is vital and often presents a major challenge.…”

Section: Actuator and Culture Chamber Designmentioning

confidence: 99%

“…Preclinical and early clinical studies using these native cell sources are promising. [35][36][37][38][39][40][41][42] In the most recent clinical trial of autologous tenocyte therapy, a total of 25 patients with recalcitrant lateral epicondylitis were treated with fibroblasts isolated from biopsied anterior cruciate ligament tissue using a patented technique developed by our laboratory. We found a 60% or greater improvement in both the Quick DASH and pain assessment scores.…”

Section: Introductionmentioning

confidence: 99%

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Bioreactor Design for Tendon/Ligament Engineering

Wang

Gardiner

Lin

et al. 2013

Tissue Engineering Part B: Reviews

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Tendon and ligament injury is a worldwide health problem, but the treatment options remain limited. Tendon and ligament engineering might provide an alternative tissue source for the surgical replacement of injured tendon. A bioreactor provides a controllable environment enabling the systematic study of specific biological, biochemical, and biomechanical requirements to design and manufacture engineered tendon/ligament tissue. Furthermore, the tendon/ligament bioreactor system can provide a suitable culture environment, which mimics the dynamics of the in vivo environment for tendon/ligament maturation. For clinical settings, bioreactors also have the advantages of less-contamination risk, high reproducibility of cell propagation by minimizing manual operation, and a consistent end product. In this review, we identify the key components, design preferences, and criteria that are required for the development of an ideal bioreactor for engineering tendons and ligaments.

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“…To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound cells in culture, increased tension was also demonstrated to promote human fibroblast proliferation and mechanical strengthening. 76 Cyclically stretched fibroblasts exhibited increased migration speed and distance when compared with unstretched cells. This induced the cells to align themselves perpendicularly to the vector of applied mechanical force and was associated with reduced apoptosis via mechanisms related to the integrin (ITG) and Wingless-type mechanotransduction pathways.…”

mentioning

confidence: 94%

Mechanical Forces in Cutaneous Wound Healing: Emerging Therapies to Minimize Scar Formation

Barnes

Marshall

Leavitt

et al. 2018

Advances in Wound Care

163

131

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Significance: Excessive scarring is major clinical and financial burden in the United States. Improved therapies are necessary to reduce scarring, especially in patients affected by hypertrophic and keloid scars. Recent Advances: Advances in our understanding of mechanical forces in the wound environment enable us to target mechanical forces to minimize scar formation. Fetal wounds experience much lower resting stress when compared with adult wounds, and they heal without scars. Therapies that modulate mechanical forces in the wound environment are able to reduce scar size. Critical Issues: Increased mechanical stresses in the wound environment induce hypertrophic scarring via activation of mechanotransduction pathways. Mechanical stimulation modulates integrin, Wingless-type, protein kinase B, and focal adhesion kinase, resulting in cell proliferation and, ultimately, fibrosis. Therefore, the development of therapies that reduce mechanical forces in the wound environment would decrease the risk of developing excessive scars. Future Directions: The development of novel mechanotherapies is necessary to minimize scar formation and advance adult wound healing toward the scarless ideal. Mechanotransduction pathways are potential targets to reduce excessive scar formation, and thus, continued studies on therapies that utilize mechanical offloading and mechanomodulation are needed.

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Cyclic strain increases fibroblast proliferation, matrix accumulation, and elastic modulus of fibroblast-seeded polyurethane constructs

Cited by 137 publications

References 48 publications

Design and Performance of an Optically Accessible, Low-Volume, Mechanobioreactor for Long-Term Study of Living Constructs

Design and Performance of an Optically Accessible, Low-Volume, Mechanobioreactor for Long-Term Study of Living Constructs

Bioreactor Design for Tendon/Ligament Engineering

Mechanical Forces in Cutaneous Wound Healing: Emerging Therapies to Minimize Scar Formation

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