Abstract
The insufficient load-bearing capacity of today's tissue-engineered (TE) cartilage limits its clinical application. Focus has been on engineering cartilage with enhanced mechanical stiffness by reproducing native biochemical compositions. More recently, depth dependency of the biochemical content and the collagen network architecture has gained interest. However, it is unknown whether the mechanical performance of TE cartilage would benefit more from higher content of biochemical compositions or from achieving an appropriate collagen organization. Furthermore, the relative synthesis rate of collagen and proteoglycans during the TE process may affect implant performance. Such insights would assist tissue engineers to focus on those aspects that are most important. The aim of the present study is therefore to elucidate the relative importance of implant ground substance stiffness, collagen content, and collagen architecture of the implant, as well as the synthesis rate of the biochemical constituents for the post-implantation mechanical behavior of the implant. We approach this by computing the post-implantation mechanical conditions using a composition-based fibril-reinforced poro-viscoelastic swelling model of the medial tibia plateau. Results show that adverse implant composition and ultrastructure may lead to post-implantation excessive mechanical loads, with collagen orientation being the most critical variable. In addition, we predict that a faster synthesis rate of proteoglycans compared to that of collagen during TE culture may result in excessive loads on collagen fibers post-implantation. This indicates that even with similar final contents, constructs may behave differently depending on their development. Considering these aspects may help to engineer TE cartilage implants with improved survival rates.
Highlights
Among the main limitations of therapies such as chondroplasty for treatment for local cartilage damage is the lack of donor tissue as well as the lack of grafts that contain biologically and mechanically functional tissue (Schek et al 2004)
We investigated the role of ground substance stiffness, collagen content, and collagen architecture of Tissue engineering (TE) implants on the post-implantation mechanical condition of the implant when the implant was attached to the native tissue and mechanically loaded
In the implant with horizontally oriented primary fibers and randomly oriented secondary fibers, 1/4 native collagen content and 1/2 of the ground substance stiffness of the native tissue, primary fibers experienced an inhomogeneous strain with peak tensile strains of 9% concentrated at the superficial and middle zone, ameliorating to 4% in the deep zone (Fig. 4a top)
Summary
Among the main limitations of therapies such as chondroplasty for treatment for local cartilage damage is the lack of donor tissue as well as the lack of grafts that contain biologically and mechanically functional tissue (Schek et al 2004). Experimental and numerical studies have demonstrated that the removal of the superficial zone from normal cartilage reduces the ability of the tissue to support axial loads and retain fluids (Glaser and Putz 2002; Torzilli et al 1983; Torzilli 1993; Owen and Wayne 2006). Given these important roles of ultrastructure in load-bearing capabilities of native tissue, one of the main challenges for tissue engineering of mechanically stable cartilage is to find the cues to create an engineered tissue with the ultrastructure components and organizations similar to those of native tissue
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