Engineering an extracellular matrix-functionalized,load-bearing tendon substitute for effective repair of large-to-massive tendon defects

A significant clinical challenge in large-to-massive rotator cuff tendon injuries is the need for sustaining high mechanical demands despite limited tissue regeneration,which often results in clinical repair failure with high retear rates and long-term functional deficiencies.To address this,an innovative tendon substitute named“BioTenoForce”is engineered,which uses(i)tendon extracellular matrix(tECM)’s rich biocomplexity for tendon-specific regeneration and(ii)a mechanically robust,slow degradation polyurethane elastomer to mimic native tendon’s physical attributes for sustaining long-term shoulder movement.Comprehensive assessments revealed outstanding performance of BioTenoForce,characterized by robust core-shell interfacial bonding,human rotator cuff tendon-like mechanical properties,excellent suture retention,biocompatibility,and tendon differentiation of human adipose-derived stem cells.Importantly,BioTenoForce,when used as an interpositional tendon substitute,demonstrated successful integration with regenerative tissue,exhibiting remarkable efficacy in repairing large-to-massive tendon injuries in two animal models.Noteworthy outcomes include durable repair and sustained functionality with no observed breakage/rupture,accelerated recovery of rat gait performance,and>1 cm rabbit tendon regeneration with native tendon-like biomechanical attributes.The regenerated tissues showed tendon-like,wavy,aligned matrix structure,which starkly contrasts with the typical disorganized scar tissue observed after tendon injury,and was strongly correlated with tissue stiffness.Our simple yet versatile approach offers a dual-pronged,broadly applicable strategy that overcomes the limitations of poor regeneration and stringent biomechanical requirements,particularly essential for substantial defects in tendon and other load-bearing tissues.