Three-Dimensional Bioprinting of a Structure-, Composition-, and Mechanics-Graded Biomimetic Scaffold Coated with Specific Decellularized Extracellular Matrix to Improve the Tendon-to-Bone Healing

Healingof a damaged tendon-to-bone enthesis occurs through theformation of fibrovascular scar tissue with greatly compromised histologicaland biomechanical properties instead of the regeneration of a newenthesis due to the lack of graded tissue-engineering zones in theinterface during the healing process. In the present study, a structure-,composition-, and mechanics-graded biomimetic scaffold (GBS) coatedwith specific decellularized extracellular matrix (dECM) (GBS-E) aimedto enhance its cellular differentiation inducibilities was fabricatedusing a three-dimensional (3-D) bioprinting technique. In vitro cellulardifferentiation studies showed that from the tendon-engineering zoneto the bone-engineering zone in the GBS, the tenogenic differentiationinducibility decreased in correspondence with an increase in the osteogenicdifferentiation inducibility. The chondrogenic differentiation inducibilitypeaked in the middle, which was in consistent with the graded cellularphenotypes observed in a native tendon-to-bone enthesis, while specificdECM coating from the tendon-engineering zone to the bone-engineeringzone (tendon-, cartilage-, and bone-derived dECM, respectively) furtherenhanced its cellular differentiation inducibilities (GBS-E). In arabbit rotator cuff tear model, histological analysis showed thatthe GBS-E group exhibited well-graded tendon-to-bone differentiatedproperties in the repaired interface that was similar to a nativetendon-to-bone enthesis at 16 weeks. Moreover, the biomechanical propertiesin the GBS-E group were also significantly higher than those in othergroups at 16 weeks. Therefore, our findings suggested a promisingtissue-engineering strategy for the regeneration of a complex enthesisusing a three-dimensional bioprinting technique.

Automated summary

A graded biomimetic scaffold coated with decellularized extracellular matrix was fabricated using 3-D bioprinting to enhance cellular differentiation and promote the regeneration of damaged tendon-to-bone enthesis. In a rabbit rotator cuff tear model, the GBS-E group exhibited superior tendon-to-bone differentiated properties and higher biomechanical properties compared to other groups at 16 weeks. This study offers a promising tissue-engineering strategy for the regeneration of complex enthesis using a 3-D bioprinting technique.