Abstract
There is a need for materials that are well suited for cartilage tissue engineering. Hydrogels have emerged as promising biomaterials for cartilage repair, since, like cartilage, they have high water content, and they allow cells to be encapsulated within the material in a genuinely three-dimensional microenvironment. In this study, we investigated the mechanical properties of tissue-engineered cartilage constructs using in vitro culture models incorporating human chondrocytes from osteoarthritis patients. We evaluated hydrogels formed from mixtures of photocrosslinkable gelatin-methacrylamide (Gel-MA) and varying concentrations (0–2%) of hyaluronic acid methacrylate (HA-MA). Initially, only small differences in the stiffness of each hydrogel existed. After 4 weeks of culture, and to a greater extent 8 weeks of culture, HA-MA had striking and concentration dependent impact on the changes in mechanical properties. For example, the initial compressive moduli of cell-laden constructs with 0 and 1% HA-MA were 29 and 41 kPa, respectively. After 8 weeks of culture, the moduli of these constructs had increased to 66 and 147 kPa respectively, representing a net improvement of 69 kPa for gels with 1% HA-MA. Similarly the equilibrium modulus, dynamic modulus, failure strength and failure strain were all improved in constructs containing HA-MA. Differences in mechanical properties did not correlate with glycosaminoglycan content, which did not vary greatly between groups, yet there were clear differences in aggrecan intensity and distribution as assessed using immunostaining. Based on the functional development with time in culture using human chondrocytes, mixtures of Gel-MA and HA-MA are promising candidates for cartilage tissue-engineering applications.
Highlights
Articular cartilage is a load bearing tissue
Studies to identify materials for cartilage tissue engineering commonly characterise the mechanical properties of cell-free scaffolds or hydrogels, but frequently do not examine how the mechanical properties change with time [3]
We evaluated hydrogels formed from mixtures of photocrosslinkable derivatives of gelatin and Hyaluronic acid (HA) (gelatin-methacrylamide (Gel-MA) and HA-methacrylate (HA-MA), respectively)
Summary
Articular cartilage is a load bearing tissue. In articulating joints, cartilage provides low friction surfaces for efficient movement, and effective impact absorption and load dissipation. Cartilage is susceptible to damage, and has a very limited capacity to heal. To address this clinical need, researchers and clinicians have developed methods to potentially regenerate or tissue-engineer new cartilage, but currently there remains a shortage of materials that are well suited for guiding effective regeneration of high quality, hyaline cartilage [1]. The mechanical properties of cartilage are crucial to its ability to withstand the compressive and shear loads to which it is routinely subjected in the joint environment. While the optimal mechanical properties for a cartilage scaffold or tissue engineered cartilage are not known, healthy cartilage is a common reference, which has an equilibrium compressive modulus in the order of 0.1–2 MPa, varying significantly with depth from the articular surface [4]. Implanting a construct that has matured for four weeks in vitro showed better integration with the surrounding cartilage compared to implanting a freshly crosslinked construct [5], which may be partially a result of the mechanical properties developed over four weeks culture protecting the construct from damage once implanted
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