Functional tissue engineering of tendon: Establishing biological success criteria for improving tendon repair

Abstract

Improving tendon repair using Functional Tissue Engineering (FTE) principles has been the focus of our laboratory over the last decade. Although our primary goals were initially focused only on mechanical outcomes, we are now carefully assessing the biological properties of our tissue-engineered tendon repairs so as to link biological influences with mechanics. However, given the complexities of tendon development and healing, it remains challenging to determine which aspects of tendon biology are the most important to focus on in the context of tissue engineering. To address this problem, we have formalized a strategy to identify, prioritize, and evaluate potential biological success criteria for tendon repair. We have defined numerous biological properties of normal tendon relative to cellular phenotype, extracellular matrix and tissue ultra-structure that we would like to reproduce in our tissue-engineered repairs and prioritized these biological criteria by examining their relative importance during both normal development and natural tendon healing. Here, we propose three specific biological criteria which we believe are essential for normal tendon function: 1) scleraxis-expressing cells; 2) well-organized and axially-aligned collagen fibrils having bimodal diameter distribution; and 3) a specialized tendon-to-bone insertion site. Moving forward, these biological success criteria will be used in conjunction with our already established mechanical success criteria to evaluate the effectiveness of our tissue-engineered tendon repairs.

The influence of pore size and stiffness on tenocyte bioactivity and transcriptomic stability in collagen-GAG scaffolds

“…The cellular component of tendon is primarily composed of tendon fibroblasts, or tenocytes, distributed throughout a hierarchical organization of aligned type I collagen fibers (James et al, 2008; Liu et al, 2008). Tendon and ligament injuries plague individuals from all walks of life, from elite athletes to the elderly, with more than 32 million occurrences every year in the US alone (Breidenbach et al, 2013; James et al, 2008; Liu et al, 2008; Xu and Murrell, 2008). While small tendon injuries heal spontaneously via regeneration, larger defects undergo a repair-mediated process generating fibrocartilagenous scar tissue with inferior structural and biomechanical properties.…”

Production of Highly Aligned Collagen Scaffolds by Freeze-drying of Self-assembled, Fibrillar Collagen Gels

“…Structural alignment imparts necessary mechanical strength to load bearing tissues such as skeletal muscle, cardiac muscle, the smooth muscle lining of blood vessels and intestines, ligaments, and tendons. 1–8 Cell and matrix alignment also provide a guidance field for migrating cells or cell processes, which plays an important role in tissue morphogenesis, wound healing, and tissue regeneration. 9,10 Matrix alignment can also guide tissue regeneration in neural tissues such as the spinal cord and peripheral nerves.…”

Advances in Tendon and Ligament Tissue Engineering: Materials Perspective

“…Notably, these injuries are estimated to affect 110 million people in the United States [1], and incomplete repair is associated with variable disabilities and chronic sequelae [2,3].…”

“…In these composite materials, specialised cells have been combined with biomaterials to produce complex, heterogeneous scaffolds with controlled mechanical properties [1,9]. This review will present an overview of the different approaches described to address the use of composite scaffolds for tendon and ligament tissue engineering.…”