Evolving Strategies in Mechanobiology to More Effectively Treat Damaged Musculoskeletal Tissues

Abstract

In this paper, we had four primary objectives. (1) We reviewed a brief history of the Lissner award and the individual for whom it is named, H.R. Lissner. We examined the type (musculoskeletal, cardiovascular, and other) and scale (organism to molecular) of research performed by prior Lissner awardees using a hierarchical paradigm adopted at the 2007 Biomechanics Summit of the US National Committee on Biomechanics. (2) We compared the research conducted by the Lissner award winners working in the musculoskeletal (MS) field with the evolution of our MS research and showed similar trends in scale over the past 35 years. (3) We discussed our evolving mechanobiology strategies for treating musculoskeletal injuries by accounting for clinical, biomechanical, and biological considerations. These strategies included studies to determine the function of the anterior cruciate ligament and its graft replacements as well as novel methods to enhance soft tissue healing using tissue engineering, functional tissue engineering, and, more recently, fundamental tissue engineering approaches. (4) We concluded with thoughts about future directions, suggesting grand challenges still facing bioengineers as well as the immense opportunities for young investigators working in musculoskeletal research. Hopefully, these retrospective and prospective analyses will be useful as the ASME Bioengineering Division charts future research directions.

Scaffolds for Tendon and Ligament Repair and Regeneration

“…For example, goat patellar tendon forces increase with level of activity, achieving almost 40% of failure force for vigorous ADLs 10,43 , while the anterior cruciate ligament in the same animal never exceeds 7-10% of failure force 32 . Thus, the safety factor for this tendon is only 2.5, while that of the ligament is approximately tenfold 8,10 .…”

“…Knowing these peak IVFs and the normal tendon stiffness also permits research to be conducted using novel functional tissue engineering strategies, including autologous mesenchymal stem cells, collagen scaffolds and mechanical preconditioning of the implant prior to surgery (Figures 3a and 3b) 8,10 .…”

“…Two mechanical design targets for these repairs (Figures 3a and 3b) include the need to meet and even exceed peak IVFs and to match the shape of the normal loading curve up to these peak values and beyond 8,10 . Partially-injured ligaments and tendons may tolerate the much lower peak IVFs that they routinely experience, however repeated loading can compromise the stiffness of these repairs, risking further tissue deformation.…”

“…At the same time, the device should not stretch more than within the toe region of a load-displacement curve rather than experiencing loads in the linear stiffness region (Figure 2). Tendon and ligament have normal function between 7% to 40% of failure loads depending on ligament or tendon type 8,10,32,43 . Several products used for reinforcement have strength and stiffness that are substantially less than human tendon values (Figure 5), and require being stretched substantially (30 - >100%) before developing a measurable load 18 , although a synthetic device has been designed with a short toe region and stiffness and strength that closely match human tendon properties (Figure 5) 19,51 .…”

Updates in biological therapies for knee injuries: anterior cruciate ligament

“…In phase 3, between 1995 and 2003, research moved to the tissue/cell level; nonetheless, in vivo tissue forces continued to be studied, and the first studies identifying novel therapies in tissue engineering and functional tissue engineering emerged. In phase 4, between 2004 and 2012, a progression to the tissue/cell/molecular levels has occurred in search of developing not only design criteria for tissueengineered tendon and ligament repairs, as compared with normal tissues, but also new research directions in fundamental tissue engineering at the interface of functional tissue engineering and developmental biology [8].…”