Tissue-Engineered Intrasynovial Tendons: Optimization of Acellularization and Seeding

By Zhang, Andrew Y.; Bates, Steven J. et al. | Journal of Rehabilitation Research & Development, July-August 2009 | Go to article overview

Tissue-Engineered Intrasynovial Tendons: Optimization of Acellularization and Seeding


Zhang, Andrew Y., Bates, Steven J., Morrow, Ellen, Pham, Hung, Pham, Bryant, Chang, James, Journal of Rehabilitation Research & Development


INTRODUCTION

Zone II flexor tendon injuries represent a significant challenge for hand surgeons. The superficial and deep flexor tendons in the hand travel though five zones to reach their target insertion site on the distal joints of the fingers. Zone II is located between the palmar crease and the distal portion of the middle phalanx. The flexor tendons travel within a tight fibroosseous sheath and pulley system in Zone II. Injuries in Zone II lead to scarring within this tunnel and significantly limit the range of motion of the affected finger. While techniques for Zone II repair have been refined over the last century, clinical outcomes remain poor for a substantial number of patients. In particular, two main problems exist for Zone II flexor tendon repair: (1) postoperative adhesion, or scarring, and (2) lack of appropriate tendon material for reconstruction. Although not yet used in clinical settings, a number of strategies have been sought to reduce postoperative adhesion formation [1-7]. However, the development of new materials for tendon reconstruction has not been extensively studied.

Many have attempted to use synthetic materials to bridge flexor tendon defects. A number of materials have been studied, including Dacron grafts [8], carbon fibers [9], and silastic sheets [10]. However, results for these materials have been poor with regard to healing and mechanical stability [8-10]. It has become evident that synthetic materials are so far unsuitable for tendon reconstruction.

The need for suitable "tendon-like" material has led many to advocate the use of autologous tendon grafts. Currently, autologous donor tendons include the palmaris longus, plantaris, extensor indicis proprius, extensor digiti minimi, flexor digitorum superficialis, and extensor digitorum longus tendons [11-12]. However, use of these tendons may result in significant donor site morbidity as well as limited excursion and poor digital function postoperatively [13]. Poor results have been hypothesized to occur because extrasynovial tendons are used to replace intrasynovial tendon losses. The intrasynovial tendons are lined with only a single layer of epitenon cells. Studies have suggested that intrasynovial tendons with epitenon cells employ an intrinsic mechanism of incorporation into the repair. In contrast, extrasynovial tendons act as a conduit for ingrowth of vessels and cells, primarily through adhesion formation. These differences in healing may account for the superior function of intrasynovial grafts observed in canine studies [14-15]. Recently, intrasynovial donor tendons have been harvested from the flexor digitorum longus tendons of the foot in humans [16]. While results have been favorable, with extensive tendon loss there may not be enough tendon material for reconstruction. Furthermore, donor site morbidity must be considered when harvesting autologous tendons.

Human allografts have also been used to replace tendon losses in Zone II flexor tendon injuries. While initial results were poor, a recent report of two patients receiving allograft reconstruction showed promising outcomes [17]. However, the potential for disease transmission, the need for possible immunosuppression, and bioethical concerns have made the use of allograft tendons less attractive.

Tissue engineering of flexor tendons is the next logical step in providing material for reconstruction. To date, significant research has been conducted in the engineering of bone and cartilage. However, tendon engineering has not been extensively studied. For the engineering of any tissue, two components are required: (1) an extracellular scaffold and (2) viable cells for seeding of the scaffold. The resulting engineered construct should be mechanically durable, nonimmunogenic, and able to retain in vivo sustainability. Experience with heart valve engineering has shown that an allogenic acellularized scaffold repopulated with autologous cells may produce the most reliable construct to meet the above requirements [18]. …

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