Biophysics Rules the Cell Culture but Has Yet to Reach the Clinic: Why Is That?

Guillaumin, Salomé; Sallent, Ignacio; Zeugolis, Dimitrios I.

doi:10.5435/jaaos-d-17-00324

Cited by 4 publications

(2 citation statements)

References 51 publications

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“…It is also important to consider that mechanical stimulation protocols for tenogenic phenotype maintenance and differentiation vary widely in terms of strain amplitude, frequency, loading time, substrate topography/ chemistry. This lack of standardization leads to contradictory results in the literature and hinders progress in the field and clinical translation (139) because it impairs result interpretation and comparison. Furthermore, the absence of highly specific tenogenic markers and knowledge about their spatial and temporal expression in tendon development, maturation, and injury is a drawback that needs to be urgently addressed.…”

Section: Resultsmentioning

confidence: 99%

Multifactorial bottom‐up bioengineering approaches for the development of living tissue substitutes

2019

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Bottom‐up bioengineering utilizes the inherent capacity of cells to build highly sophisticated structures with high levels of biomimicry. Despite the significant advancements in the field, monodomain approaches require prolonged culture time to develop an implantable device, usually associated with cell phenotypic drift in culture. Herein, we assessed the simultaneous effect of macromolecular crowding (MMC) and mechanical loading in enhancing extracellular matrix (ECM) deposition while maintaining tenocyte (TC) phenotype and differentiating bone marrow stem cells (BMSCs) or transdifferentiating neonatal and adult dermal fibroblasts toward tenogenic lineage. At d 7, all cell types presented cytoskeleton alignment perpendicular to the applied load independently of the use of MMC. MMC enhanced ECM deposition in all cell types. Gene expression analysis indicated that MMC and mechanical loading maintained TC phenotype, whereas tenogenic differentiation of BMSCs or transdifferentiation of dermal fibroblasts was not achieved. Our data suggest that multifactorial bottom‐up bioengineering approaches significantly accelerate the development of biomimetic tissue equivalents.—Gaspar, D., Ryan, C. N. M., Zeugolis, D. I. Multifactorial bottom‐up bioengineering approaches for the development of living tissue substitutes. FASEB J. 33, 5741–5754 (2019). http://www.fasebj.org

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Section: Resultsmentioning

confidence: 99%

Multifactorial bottom‐up bioengineering approaches for the development of living tissue substitutes

2019

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“…In vitro, although soluble factors have shown promise in controlling cell fate [5,6], the literally infinite number of potential permutations on biochemical and/or biological media supplements, concentrations, combinations, and timings has restricted their use. To this end, the use of biophysical cues has been advocated [7][8][9] and, due to simplicity, surface topography [10,11] and substrate stiffness [12,13] have been the subject of very many investigations in the quest to either maintain permanently differentiated cell phenotype (e.g., tenocyte [14,15], chondrocytes [16,17], osteoblasts [18,19]) or to direct stem cells towards a specific lineage (e.g., tenogenic [20,21], chondrogenic [22,23], osteogenic [24,25], adipogenic [26,27]). Considering though that cells in vivo are subjected simultaneously to multiple signals, mono-factorial approaches are unlikely to yield a functional output (e.g., 85/15 poly(lactic-co-glycolic acid) with anisotropic grooves, although resulted in upregulation of tendon genes, due to its high rigidity, also induced upregulation of bone and cartilage genes [28]), which has triggered investigations into multi-factorial tissue engineering [29][30][31].…”

Section: Introductionmentioning

confidence: 99%

Assessing the combined effect of surface topography and substrate rigidity in human bone marrow stem cell cultures

Ribeiro

Pugliese

Korntner

et al. 2022

Engineering in Life Sciences

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The combined effect of surface topography and substrate rigidity in stem cell cultures is still under-investigated, especially when biodegradable polymers are used. Herein, we assessed human bone marrow stem cell response on aliphatic polyester substrates as a function of anisotropic grooved topography and rigidity (7 and 12 kPa). Planar tissue culture plastic (TCP, 3 GPa) and aliphatic polyester substrates were used as controls. Cell morphology analysis revealed that grooved substrates caused nuclei orientation/alignment in the direction of the grooves.After 21 days in osteogenic and chondrogenic media, the 3 GPa TCP and the grooved 12 kPa substrate induced significantly higher calcium deposition and alkaline phosphatase (ALP) activity and glycosaminoglycan (GAG) deposition, respectively, than the other groups. After 14 days in tenogenic media, the 3 GPa TCP upregulated four and downregulated four genes; the planar 7 kPa substrate

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Designing Microenvironments for Optimal Outcomes in Tissue Engineering and Regenerative Medicine: From Biopolymers to Culturing Conditions

Tsiapalis

Ribeiro

Pieri

et al. 2019

Reference Module in Biomedical Sciences

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Bone marrow mesenchymal stem cells have been extensively used for tissue engineering and regenerative medicine applications due to their ease of isolation and expansion and their ability to differentiate towards various lineages of mesodermal origin. Despite these properties, their clinical potential is often hampered by the simplicity of the in vitro environment and its inability to resemble the complex in vivo niche. Herein, different microenvironmental cues (e.g. surface topography, substrate stiffness, mechanical stimulation, oxygen tension and co-culture systems) that have been utilised to enhance the therapeutic efficacy of bone marrow mesenchymal stem cells are discussed.

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Biophysics Rules the Cell Culture but Has Yet to Reach the Clinic: Why Is That?

Cited by 4 publications

References 51 publications

Multifactorial bottom‐up bioengineering approaches for the development of living tissue substitutes

Multifactorial bottom‐up bioengineering approaches for the development of living tissue substitutes

Assessing the combined effect of surface topography and substrate rigidity in human bone marrow stem cell cultures

Designing Microenvironments for Optimal Outcomes in Tissue Engineering and Regenerative Medicine: From Biopolymers to Culturing Conditions

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