Facile and rapid fabrication of a novel 3D-printable,visible light-crosslinkable and bioactive polythiourethane for large-to-massive rotator cuff tendon repair

Facile and rapid 3D fabrication of strong,bioactive materials can address challenges that impede repair of large-to-massive rotator cuff tears including personalized grafts,limited mechanical support,and inadequate tissue regeneration.Herein,we developed a facile and rapid methodology that generates visible light-crosslinkable polythiourethane(PHT)pre-polymer resin(~30 min at room temperature),yielding 3D-printable scaffolds with tendon-like mechanical attributes capable of delivering tenogenic bioactive factors.Ex vivo characterization confirmed successful fabrication,robust human supraspinatus tendon(SST)-like tensile properties(strength:23 MPa,modulus:459 MPa,at least 10,000 physiological loading cycles without failure),excellent suture retention(8.62-fold lower than acellular dermal matrix(ADM)-based clinical graft),slow degradation,and controlled release of fibroblast growth factor-2(FGF-2)and transforming growth factor-β3(TGF-β3).In vitro studies showed cytocompatibility and growth factor-mediated tenogenic-like differentiation of mesenchymal stem cells.In vivo studies demonstrated biocompatibility(3-week mouse subcutaneous implantation)and ability of growth factor-containing scaffolds to notably regenerate at least 1-cm of tendon with native-like biomechanical attributes as uninjured shoulder(8-week,large-to-massive 1-cm gap rabbit rotator cuff injury).This study demonstrates use of a 3D-printable,strong,and bioactive material to provide mechanical support and pro-regenerative cues for challenging injuries such as large-to-massive rotator cuff tears.

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.