Extracellular Matrix Hydrogels Promote Expression of Muscle-Tendon Junction Proteins.

Muscle and tendon injuries are prevalent and range from minor sprains and strains to traumatic, debilitating injuries. However, the interactions between these tissues during injury and recovery remain unclear. Three-dimensional tissue models that incorporate both tissues and a physiologically relevant junction between muscle and tendon may help understand how the two tissues interact. Here, we use tissue specific extracellular matrix (ECM) derived from muscle and tendon to determine how cells of each tissue interact with the microenvironment of the opposite tissue, resulting in junction-specific features. The ECM materials were derived from the Achilles tendon and gastrocnemius muscle, decellularized, and processed to form tissue-specific pre-hydrogel digests. The ECM materials were unique in respect to protein composition and included many types of ECM proteins, not just collagens. After digestion and gelation, ECM hydrogels had similar complex viscosities that were less than type I collagen hydrogels at the same concentration. C2C12 myoblasts and tendon fibroblasts were cultured in tissue-specific ECM conditioned media or encapsulated in tissue-specific ECM hydrogels to determine cell-matrix interactions and the effects on a muscle-tendon junction marker, paxillin. The ECM conditioned media had only a minor effect on the upregulation of paxillin in cells cultured in monolayer. However, cells cultured within ECM hydrogels had 50-70% higher paxillin expression than cells cultured in type I collagen hydrogels. Contraction of the ECM hydrogels varied by the type of ECM used. Subsequent experiments with a varying density of type I collagen (and thus contraction) showed no correlation between paxillin expression and the amount of gel contraction, suggesting that a constituent of the ECM was the driver of paxillin expression in the ECM hydrogels. In addition, another junction marker, type XXII collagen, had similar expression patterns as paxillin, with smaller effect sizes. Using tissue-specific ECM allowed for the de-construction of the cell-matrix interactions similar to muscle-tendon junctions to study the expression of myotendinous junction-specific proteins. Impact statement The muscle-tendon junction is an important feature of muscle-tendon units; however, despite crosstalk between the two tissue types, the junction is often overlooked in current research. Deconstructing the cell-matrix interactions will provide the opportunity to study significant junction-specific features and markers that should be included in tissue models of the muscle-tendon unit, while gaining a deeper understanding of the natural junction. This research aims at informing future methods to engineer a more relevant multi-tissue platform to study the muscle-tendon unit.

Effect of bite depth of an epitendinous suture on the biomechanical strength of repaired canine flexor tendons.

OBJECTIVE: To determine effects of bite depth for placement of an epitendinous suture on the biomechanical strength and gap formation of repaired canine tendons. SAMPLE: 48 superficial digital flexor tendons (SDFTs) obtained from 24 canine cadavers. PROCEDURES: Tendons were assigned to 3 groups (16 tendons/group). Each SDFT was transected and then repaired with a continuous epitendinous suture placed with a bite depth of 1, 2, or 3 mm for groups 1, 2, and 3, respectively. Specimens were loaded to failure. Failure mode, gap formation, yield force, peak force, and failure force were analyzed. RESULTS: Yield, peak, and failure forces differed significantly between groups 1 and 3 and groups 2 and 3 but not between groups 1 and 2. Comparison of the force resisted at 1 and 3 mm of gapping revealed a significant difference between groups 1 and 3 and groups 2 and 3 but not between groups 1 and 2. Failure mode did not differ among groups; suture pull-through occurred in 43 of 48 (89.6%) specimens. CONCLUSIONS AND CLINICAL RELEVANCE: Increasing bite depth of an epitendinous suture toward the center of the tendon substance increased repair site strength and decreased the incidence of gap formation. Repair of tendon injuries in dogs by use of an epitendinous suture with bites made deep into the tendon should result in a stronger repair, which potentially would allow loading and rehabilitation to begin sooner after surgery. Suture techniques should be investigated in vivo to determine effects on tendinous healing and blood supply before clinical implementation.