Tissue-Engineering Strategies for the Tendon/Ligament-to-Bone Insertion

Abstract

Injuries to connective tissues are painful and disabling and result in costly medical expenses. These injuries often require re-attachment of an unmineralized connective tissue to bone. The uninjured tendon/ligament-to-bone insertion (enthesis) is a functionally graded material that exhibits a gradual transition from soft tissue (i.e., tendon or ligament) to hard tissue (i.e., mineralized bone) through a fibrocartilaginous transition region. This transition is believed to facilitate force transmission between the two dissimilar tissues by ameliorating potentially damaging interfacial stress concentrations. The transition region is impaired or lost upon tendon/ligament injury and is not regenerated following surgical repair or natural healing, exposing the tissue to risk of re-injury. The need to regenerate a robust tendon-to-bone insertion has led a number of tissue engineering repair strategies. This review treats the tendon-to-bone insertion site as a tissue structure whose primary role is mechanical and discusses current and emerging strategies for engineering the tendon/ligament-to-bone insertion in this context. The focus lies on strategies for producing mechanical structures that can guide and subsequently sustain a graded tissue structure and the associated cell populations.

Scaffold-mediated lentiviral transduction for functional tissue engineering of cartilage

“…To circumvent this, future studies may be directed toward the replacement of the constitutive EF-1α promoter with a drug-inducible promoter (61), which could confer engineered control of the duration and magnitude of transgene expression. Moreover, the technique of biomaterial-mediated gene delivery may be applied toward engineering complex tissues or tissue interfaces for regenerative medicine (62)(63)(64).…”

Stretchable heterogeneous composites with extreme mechanical gradients

“…Obtaining such level of 3D control in artificial heterogeneous composites would allow us to not only extend the lifetime of existing functional devices prone to interfacial failure but also to develop new materials for mechanically challenging demands. These include for example dental restorations for prosthetic dentistry that more closely resemble the mechanical properties of natural tooth 23 , elastomeric substrates for flexible electronics that are bendable and stretchable but yet locally stiff [24][25][26][27][28][29] and synthetic bioscaffolds for the replacement of intervertebral discs 30 and for the regeneration of graded tendon/ligament-to-bone insertions [31][32][33] . In addition to addressing such mechanical challenges, the deliberate local reinforcement of weak regions achievable with such heterogeneous composites also represents an economical and environmental-friendly approach to attain the required mechanical performance while minimizing the use of limited and costly resources.…”

Multiphase Biodegradable Scaffolds for Tissue Engineering a Tendon-Bone Junction

“…Tendon tears have a poor healing capacity, and the most common tendon bone junction injuries are at the Achilles tendon, the rotator cuff and the anterior cruciate ligament (ACL). Every year there are about 100,000 ACL reconstructive surgeries, 75,000 rotator cuff repairs and 230,000 Achilles tendon repairs performed in the United States [1,2].…”

“…Thus, one of the most immediate challenges facing the field of regenerative medicine is "Interfacial Tissue Engineering" (ITE), which addresses the question of how to generate a multiple tissue junction such as a tendon-bone interface which has integrity, continuity and consists of at least two different yet contiguous types of cells, including tenocytes and osteoblasts [1]. Research to date has taken the approach that it is necessary to use pluripotent stem cells or to co-culture the two dissimilar cell lines either sequentially or together in a single compromised media and under coculture conditions [1,[3][4][5]. This simplistic approach assumes that a tissue junction consists of only two types of cells that join at the interface.…”