Mechanical Testing of Hydrogels in Cartilage Tissue Engineering: Beyond the Compressive Modulus

Xiao, Yinghua; Friis, Elizabeth A.; Gehrke, Stevin H.; Detamore, Michael S.

doi:10.1089/ten.teb.2012.0461

Cited by 59 publications

(49 citation statements)

References 47 publications

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“…However, it must be noted that biomechanical properties of cartilage can vary depending on parameters such as the method of testing, the strain rate of testing, and cartilage zone depth [38]. Although certainly other mechanical properties have been explored and analyzed in cartilage tissue engineering, including the aggregate modulus, hydraulic permeability, and fracture stress [35, 39], in the current study the compressive modulus and the overall stress-strain profile of the gel constructs were the primary emphases. Gels composed entirely of crosslinked solubilized cartilage matrix were created that had a compressive modulus in the same range of values reported for native cartilage.…”

Section: Discussionmentioning

confidence: 99%

“…Although the 20% gels fractured early at 7.5% strain, the fact that they fell within the stress strain profile of native cartilage tissue was promising. Certainly the early fracture stress needs to be addressed, however [39]. Furthermore, the early fracture stress precluded time-dependent property analysis, which will be important to consider for future work with these materials to better understand their viscoelastic behavior.…”

Section: Discussionmentioning

confidence: 99%

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Approaching the compressive modulus of articular cartilage with a decellularized cartilage-based hydrogel

et al. 2016

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ECM-based materials are appealing for tissue engineering strategies because they may promote stem cell recruitment, cell infiltration, and cell differentiation without the need to supplement with additional biological factors. Cartilage ECM has recently shown potential to be chondroinductive, particularly in a hydrogel-based system, which may be revolutionary in orthopedic medicine. However, hydrogels composed of natural materials are often mechanically inferior to synthetic materials, which is a major limitation for load-bearing tissue applications. The objective was therefore to create an unprecedented hydrogel derived entirely from native cartilage ECM that was both mechanically more similar to native cartilage tissue and capable of inducing chondrogenesis. Porcine cartilage was decellularized, solubilized, and then methacrylated and UV photocrosslinked to create methacrylated solubilized decellularized cartilage (MeSDCC) gels. Methacrylated gelatin (GelMA) was employed as a control for both biomechanics and bioactivity. Rat bone marrow-derived mesenchymal stem cells were encapsulated in these networks, which were cultured in vitro for 6 weeks, where chondrogenic gene expression, the compressive modulus, swelling, and histology were analyzed. One day after crosslinking, the elastic compressive modulus of the 20% MeSDCC gels was 1070 ± 150 kPa. Most notably, the stress strain profile of the 20% MeSDCC gels fell within the 95% confidence interval range of native porcine cartilage. Additionally, MeSDCC gels significantly upregulated chondrogenic genes compared to GelMA as early as day 1 and supported extensive matrix synthesis as observed histologically. Given that these gels approached the mechanics of native cartilage tissue, supported matrix synthesis, and induced chondrogenic gene expression, MeSDCC hydrogels may be promising materials for cartilage tissue engineering applications. Future efforts will focus on improving fracture mechanics as well to benefit overall biomechanical performance.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Approaching the compressive modulus of articular cartilage with a decellularized cartilage-based hydrogel

et al. 2016

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“…Nonetheless, it may not be necessary to match all of the material properties of native tissue a priori in view of the remodeling potential of the implanted tissue in vivo (Schmidt et al, 2010). Priority has often been placed on a single parameter such as the compressive or tensile modulus of a tissue (Butler et al, 2008; Xiao et al, 2013), yet the relative importance of all of the different properties of a tissue or its constituents is unknown. To better understand and refine these design criteria, it will be necessary to understand the trade-offs and interactions of different functional characteristics and the overall success criteria of the implant.…”

Section: Principles Of Functional Tissue Engineeringmentioning

confidence: 99%

Biomechanics and mechanobiology in functional tissue engineering

Guilak

Butler

Goldstein

et al. 2014

Journal of Biomechanics

198

127

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The field of tissue engineering continues to expand and mature, and several products are now in clinical use, with numerous other preclinical and clinical studies underway. However, specific challenges still remain in the repair or regeneration of tissues that serve a predominantly biomechanical function. Furthermore, it is now clear that mechanobiological interactions between cells and scaffolds can critically influence cell behavior, even in tissues and organs that do not serve an overt biomechanical role. Over the past decade, the field of “functional tissue engineering” has grown as a subfield of tissue engineering to address the challenges and questions on the role of biomechanics and mechanobiology in tissue engineering. Originally posed as a set of principles and guidelines for engineering of load-bearing tissues, functional tissue engineering has grown to encompass several related areas that have proven to have important implications for tissue repair and regeneration. These topics include measurement and modeling of the in vivo biomechanical environment; quantitative analysis of the mechanical properties of native tissues, scaffolds, and repair tissues; development of rationale criteria for the design and assessment of engineered tissues; investigation of the effects biomechanical factors on native and repair tissues, in vivo and in vitro; and development and application of computational models of tissue growth and remodeling. Here we further expand this paradigm and provide examples of the numerous advances in the field over the past decade. Consideration of these principles in the design process will hopefully improve the safety, efficacy, and overall success of engineered tissue replacements.

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“…46,[61][62][63][64][65][66] In this study, we report an extensive set of properties; nevertheless, an additional useful measure of mechanical integrity of constructs is their failure response. 67 Although we did not measure failure properties in the current study, we have thusly characterized chondrocyte-seeded agarose constructs in previous work. 34,68 As we further improve culture conditions in this model system, we expect to characterize failure properties systematically before in vivo implantation of constructs.…”

Section: Discussionmentioning

confidence: 99%

Nutrient Channels Aid the Growth of Articular Surface-Sized Engineered Cartilage Constructs

Cigáň

Durney

Nims

et al. 2016

Tissue Engineering Part A

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Mechanical Testing of Hydrogels in Cartilage Tissue Engineering: Beyond the Compressive Modulus

Cited by 59 publications

References 47 publications

Approaching the compressive modulus of articular cartilage with a decellularized cartilage-based hydrogel

Approaching the compressive modulus of articular cartilage with a decellularized cartilage-based hydrogel

Biomechanics and mechanobiology in functional tissue engineering

Nutrient Channels Aid the Growth of Articular Surface-Sized Engineered Cartilage Constructs

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