Tendon/Ligament-to-Bone Tissue Engineering— Current and Emerging Strategies

Lester Smith, Stavros Thomopoulos
US Musculoskeletal Review, 2011;6(1):11-5
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Abstract

Connective tissue injuries are a common cause of pain and disability and lead to significant medical costs. These injuries often require reattachment of a soft tissue to bone. The tendon/ligament-to-bone insertion is a functionally graded material that exhibits a gradual transition from soft (i.e. tendon or ligament) to mineralized (i.e. bone) tissue, with no clear borders between tissue regions. The fibrocartilaginous transition region between tendon and bone permits force transmission between two tissues with disparate mechanical properties while mitigating potentially damaging stress concentrations. This transitional region is lost on tendon/ligament injury and is not recreated following surgical repair or natural healing, putting the repair tissue at risk for re-injury and/or chronic pain. The need to recreate a robust transition tissue has led to investigations of tissue-engineered repair strategies. Here, we review current approaches and discuss emerging strategies for tendon/ligament-to-bone tissue engineering.
Keywords
Tendon-to-bone, ligament-to-bone, insertion, fibrocartilage, enthesis, gradient, stratified
Disclosure The authors have no conflicts of interest to declare.
Received: April 18, 2011 Accepted May 20, 2011
Correspondence: Stavros Thomopoulos, PhD, Washington University, Department of Orthopaedic Surgery, 660 South Euclid, Campus Box 8233, St Louis, MO 63110. E: ThomopoulosS@wudosis.wustl.edu

Tendon/Ligament-to-bone Insertion Structure and Function
The tendon/ligament-to-bone insertion is a functionally graded material that exhibits a gradual transition from unmineralized (i.e. tendon or ligament) to mineralized (i.e. bone) tissue, with no clear borders between tissue regions.1–14 Tendon/ligament transitions into fibrocartilage, which transitions into mineralized fibrocartilage, which transitions into bone (see Figure 1). Tendons and ligaments are composed of collagen type I aligned in highly ordered arrays oriented in the direction of force. Fibrocartilage is primarily composed of collagen type II (typically seen in articular cartilage) with significant amounts of collagen type III and small amounts of collagen types I and X, decorin, and aggrecan.2,15 The mineralized fibrocartilage is primarily composed of collagen type II with large amounts of collagen type X16 and appreciable levels of aggrecan. Mineralized fibrocartilage exhibits less fibril alignment than do fibrocartilage and tendon proper.2 Finally, bone is composed of highly mineralized collagen type I matrix. The insertion site therefore exhibits a graded increase in mineralization and a graded decrease in tissue organization from tendon/ligament to bone.2 Instead of the potentially damaging stress concentrations that would arise at an abrupt interface between a soft tissue and a bone, compositional and organizational gradations through the transitional region mitigate stress concentrations and enable the safe transmission of forces.2

Current Surgical Approaches
Rotator Cuff
The rotator cuff provides stability and motion at the glenohumeral joint.17Injuries to the rotator cuff can involve one or more tendon tears from the humeral head. The incidence of tears is high; approximately 30% of the population over 60 years of age has a rotator cuff tear.18,19 It is the most common shoulder condition, with more than 17 million individuals in the US affected.18 Rotator cuff repair to recover shoulder function is one of the most common orthopaedic surgical procedures, with over 75,000 repairs performed each year in the US.20 Healing after rotator cuff repair is a well-known clinical challenge. Tears occur at or near the tendon-to-bone insertion site, and the goal of rotator cuff repair is anatomic restoration of the tendon attachment.

However, clinical studies have shown failure rates ranging from 30 to 94%.4,21 Surgical repair typically involves securing the tendon to the humeral head with sutures and suture anchors. Although the tendons are effectively re-apposed to their anatomic footprints, the functionally graded transitional tissue found at the uninjured interface is not regenerated. Further complicating the outcome is the common presentation of chronic injuries; this delay often results in tendon retraction22 and osteolysis3 at the insertion site, effectively shortening the tendon and leaving poor quality bone tissue available for fixation. A recent review of the scaffolds currently used clinically for rotator cuff repair revealed that further work is necessary to optimize scaffold properties.22 Particularly lacking in the currently available scaffolds is an appropriate recreation of the gradation properties of the native tissue.

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