Slow stretching that mimics embryonic growth rate stimulates structural and mechanical development of tendon‐like tissue in vitro

Kalson, Nicholas S.; Holmes, David; Herchenhan, Andreas; Lu, Yinhui; Starborg, Tobias; Kadler, Karl E.

doi:10.1002/dvdy.22760

Cited by 68 publications

(62 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another study used a gel-nanofiber model to demonstrate that a nanoscale tip probes single collagen fibrils and proteoglycan components of cartilage, whereas a microscale tip measures a cross-linked network (28). Accordingly, nanoscale moduli were, on average, two-to threefold lower than microscale moduli in our study, and both were one to three orders of magnitude below reported chick tendon bulk tensile moduli (8,33). We also measured an increase in the SD of average Fig.…”

Section: Discussionsupporting

confidence: 51%

Characterization of mechanical and biochemical properties of developing embryonic tendon

Marturano

Arena

Schiller

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

165

277

View full text Add to dashboard Cite

Tendons have uniquely high tensile strength, critical to their function to transfer force from muscle to bone. When injured, their innate healing response results in aberrant matrix organization and functional properties. Efforts to regenerate tendon are challenged by limited understanding of its normal development. Consequently, there are few known markers to assess tendon formation and parameters to design tissue engineering scaffolds. We profiled mechanical and biological properties of embryonic tendon and demonstrated functional properties of developing tendon are not wholly reflected by protein expression and tissue morphology. Using force volume-atomic force microscopy, we found that nano-and microscale tendon elastic moduli increase nonlinearly and become increasingly spatially heterogeneous during embryonic development. When we analyzed potential biochemical contributors to modulus, we found statistically significant but weak correlation between elastic modulus and collagen content, and no correlation with DNA or glycosaminoglycan content, indicating there are additional contributors to mechanical properties. To investigate collagen cross-linking as a potential contributor, we inhibited lysyl oxidasemediated collagen cross-linking, which significantly reduced tendon elastic modulus without affecting collagen morphology or DNA, glycosaminoglycan, and collagen content. This suggests that lysyl oxidase-mediated cross-linking plays a significant role in the development of embryonic tendon functional properties and demonstrates that changes in cross-links alter mechanical properties without affecting matrix content and organization. Taken together, these data demonstrate the importance of functional markers to assess tendon development and provide a profile of tenogenic mechanical properties that may be implemented in tissue engineering scaffold design to mechanoregulate new tendon regeneration.musculoskeletal | second harmonic generation T endon is a principal tissue involved in movement, functioning primarily to transfer loads from muscle to bone. Acute and chronic tendon injuries are significant clinical problems due to poor innate healing ability and drawbacks associated with surgical repair (1, 2). In 2006, musculoskeletal symptoms were the second most frequent reason for physician visits in the United States, resulting in over 130 million visits at a cost of nearly $850 billion (3). Almost half of these visits involved tendons and ligaments, with incidence expected to rise with an aging population. Thus, efforts have focused on engineering new tissues for replacement, although this has been challenged by a paucity of markers with which to assess functional tendon development and few known cues to direct differentiation and new tissue formation.Characterization of tendon formation in embryonic or engineered tissue has typically relied on molecular markers, as well as matrix composition and organization (4-9). Although useful for assessing cell differentiation and ECM deposition during tissue formation, t...

show abstract

Section: Discussionsupporting

confidence: 51%

Characterization of mechanical and biochemical properties of developing embryonic tendon

Marturano

Arena

Schiller

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

165

277

View full text Add to dashboard Cite

show abstract

“…The Role of Loading in Tendon Development and Homeostasis Tendon Development Mechanical forces during development are vital to successful limb and musculoskeletal tissue formation during embryogenesis [17][18][19][20][21][22][23][24] .…”

Section: Tendon Structure and Functionmentioning

confidence: 99%

“…For example, the menisci of the tibiofemoral joint and the plantar tarsal sesamoid of the tibiotarsal joint fail to form, suggesting the inability of tendinous structures to form properly in the absence of mechanical loading and the importance of mechanical stress for proper musculoskeletal development 18 . It is postulated that embryonic and early postnatal growth of tendon relies on the generation of two types of stresses: rapid muscular activity and slow, growth-related elongation of bone 21 . Early in tendon development, the collagen fibril diameter is characterized as a homogeneous distribution of small fibrils (ranging from approximately 40 to 75 nm).…”

Section: Tendon Structure and Functionmentioning

confidence: 99%

The Role of Mechanical Loading in Tendon Development, Maintenance, Injury, and Repair

Galloway

Lalley

Shearn

2013

Journal of Bone and Joint Surgery

212

192

View full text Add to dashboard Cite

“…23,24 Alternatively, fibrin gels have been recently proposed for creating tissue constructs in vitro, as fibrin promotes greater collagen synthesis than collagen gels and more readily remodels according to the physical boundary conditions of the construct apparatus. [25][26][27] Cells in fibrin gels also appear to recapitulate aspects of native tendon development in vitro 28,29 and exhibit improved cell-derived collagen organization in response to mechanical stimulation. 30,31 However, research has not yet been conducted that directly compares how collagen and fibrin materials affect the ability of TLPs to respond to mechanical stimuli and produce an organized ECM.…”

Section: Introductionmentioning

confidence: 99%

Fibrin Gels Exhibit Improved Biological, Structural, and Mechanical Properties Compared with Collagen Gels in Cell-Based Tendon Tissue-Engineered Constructs

Breidenbach

Dyment

et al. 2015

Tissue Engineering Part A

Self Cite

View full text Add to dashboard Cite

The prevalence of tendon and ligament injuries and inadequacies of current treatments is driving the need for alternative strategies such as tissue engineering. Fibrin and collagen biopolymers have been popular materials for creating tissue-engineered constructs (TECs), as they exhibit advantages of biocompatibility and flexibility in construct design. Unfortunately, a few studies have directly compared these materials for tendon and ligament applications. Therefore, this study aims at determining how collagen versus fibrin hydrogels affect the biological, structural, and mechanical properties of TECs during formation in vitro. Our findings show that tendon and ligament progenitor cells seeded in fibrin constructs exhibit improved tenogenic gene expression patterns compared with their collagen-based counterparts for approximately 14 days in culture. Fibrin-based constructs also exhibit improved cell-derived collagen alignment, increased linear modulus (2.2-fold greater) compared with collagen-based constructs. Cyclic tensile loading, which promotes the maturation of tendon constructs in a previous work, exhibits a material-dependent effect in this study. Fibrin constructs show trending reductions in mechanical, biological, and structural properties, whereas collagen constructs only show improved tenogenic expression in the presence of mechanical stimulation. These findings highlight that components of the mechanical stimulus (e.g., strain amplitude or time of initiation) need to be tailored to the material and cell type. Given the improvements in tenogenic expression, extracellular matrix organization, and material properties during static culture, in vitro findings presented here suggest that fibrin-based constructs may be a more suitable alternative to collagen-based constructs for tissue-engineered tendon/ligament repair.

show abstract

Slow stretching that mimics embryonic growth rate stimulates structural and mechanical development of tendon‐like tissue in vitro

Cited by 68 publications

References 31 publications

Characterization of mechanical and biochemical properties of developing embryonic tendon

Characterization of mechanical and biochemical properties of developing embryonic tendon

The Role of Mechanical Loading in Tendon Development, Maintenance, Injury, and Repair

Fibrin Gels Exhibit Improved Biological, Structural, and Mechanical Properties Compared with Collagen Gels in Cell-Based Tendon Tissue-Engineered Constructs

Contact Info

Product

Resources

About