3-Dimensional Bioprinting of a Tendon Stem Cell-Derived Exosomes Loaded Scaffold to Bridge the Unrepairable Massive Rotator Cuff Tear.

BACKGROUND: Unrepairable massive rotator cuff tears (UMRCTs) are challenging to surgeons owing to the severely retracted rotator cuff musculotendinous tissues and extreme defects in the rotator cuff tendinous tissues. PURPOSE: To fabricate a tendon stem cell-derived exosomes loaded scaffold (TSC-Exos-S) and investigate its effects on cellular bioactivity in vitro and repair in a rabbit UMRCT model in vivo. STUDY DESIGN: Controlled laboratory study. METHODS: TSC-Exos-S was fabricated by loading TSC-Exos and type 1 collagen (COL-I) into a 3-dimensional bioprinted and polycaprolactone (PCL)-based scaffold. The proliferation, migration, and tenogenic differentiation activities of rabbit bone marrow stem cells (BMSCs) were evaluated in vitro by culturing them in saline, PCL-based scaffold (S), COL-I loaded scaffold (COL-I-S), and TSC-Exos-S. In vivo studies were conducted on a rabbit UMRCT model, where bridging was repaired with S, COL-I-S, TSC-Exos-S, and autologous fascia lata (FL). Histological and biomechanical analyses were performed at 8 and 16 weeks postoperatively. RESULTS: TSC-Exos-S exhibited reliable mechanical strength and subcutaneous degradation, which did not occur before tissue regeneration. TSC-Exos-S significantly promoted the proliferation, migration, and tenogenic differentiation of rabbit BMSCs in vitro. In vivo studies showed that UMRCT repaired with TSC-Exos-S exhibited significant signs of tendinous tissue regeneration at the bridging site with regard to specific collagen staining. Moreover, no significant differences were observed in the histological and biomechanical properties compared with those repaired with autologous FL. CONCLUSION: TSC-Exos-S achieved tendinous tissue regeneration in UMRCT by providing mechanical support and promoting the trend toward tenogenic differentiation. CLINICAL RELEVANCE: The present study proposes a potential strategy for repairing UMRCT with severely retracted musculotendinous tissues and large tendinous tissue defects.

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.

Healing of a damaged tendon-to-bone enthesis occurs through the formation of fibrovascular scar tissue with greatly compromised histological and biomechanical properties instead of the regeneration of a new enthesis due to the lack of graded tissue-engineering zones in the interface during the healing process. In the present study, a structure-, composition-, and mechanics-graded biomimetic scaffold (GBS) coated with specific decellularized extracellular matrix (dECM) (GBS-E) aimed to enhance its cellular differentiation inducibilities was fabricated using a three-dimensional (3-D) bioprinting technique. In vitro cellular differentiation studies showed that from the tendon-engineering zone to the bone-engineering zone in the GBS, the tenogenic differentiation inducibility decreased in correspondence with an increase in the osteogenic differentiation inducibility. The chondrogenic differentiation inducibility peaked in the middle, which was in consistent with the graded cellular phenotypes observed in a native tendon-to-bone enthesis, while specific dECM coating from the tendon-engineering zone to the bone-engineering zone (tendon-, cartilage-, and bone-derived dECM, respectively) further enhanced its cellular differentiation inducibilities (GBS-E). In a rabbit rotator cuff tear model, histological analysis showed that the GBS-E group exhibited well-graded tendon-to-bone differentiated properties in the repaired interface that was similar to a native tendon-to-bone enthesis at 16 weeks. Moreover, the biomechanical properties in the GBS-E group were also significantly higher than those in other groups at 16 weeks. Therefore, our findings suggested a promising tissue-engineering strategy for the regeneration of a complex enthesis using a three-dimensional bioprinting technique.

Tendon-bone healing enhancement using injectable tricalcium phosphate in a dog anterior cruciate ligament reconstruction model.

PURPOSE: The purpose of this study was to evaluate the enhancement potential of injectable tricalcium phosphate (TCP) for tendon-bone healing in anterior cruciate ligament (ACL) reconstruction in a dog model. METHODS: In this experimental study ACL reconstruction was performed on both knees of 48 beagle dogs with the tendon of the flexor digitorum longus. A suspension fixation technique was used, and the tendon graft filled only the tunnel parts near the joint. On the experimental side, in addition to ACL reconstruction, injectable TCP was used to fill those tunnel parts that were not filled by the graft. On the other side, no additional treatment was applied (control). At 2, 4, 6, 8, 10, and 12 weeks postoperatively, 8 dogs were killed, respectively, with 3 for histologic observation at the proximal tendon-bone junction and 5 for mechanical examination. RESULTS: Histologic observation showed that on the experimental side, Sharpey fibers, fibrocartilage, and calcified cartilage appear earlier at the tendon-bone interface and tendon-bone healing proceeded more quickly than on the control side. Mechanical examination showed that within 4 weeks, the pullout strength was higher on the experimental side than on the control side, and there was a statistically significant difference between the results. CONCLUSIONS: Filling the bone tunnel with TCP after inserting the ACL graft results in faster incorporation of the graft to the tunnel, with better biomechanical properties and a more mature histologic pattern. CLINICAL RELEVANCE: If these results are clinically applicable, rapid tendon-bone healing may be expected in ACL reconstruction.

Biological augmentation of rotator cuff repair using bFGF-loaded electrospun poly(lactide-co-glycolide) fibrous membranes.

Clinically, rotator cuff tear (RCT) is among the most common shoulder pathologies. Despite significant advances in surgical techniques, the re-tear rate after rotator cuff (RC) repair remains high. Insufficient healing capacity is likely the main factor for reconstruction failure. This study reports on a basic fibroblast growth factor (bFGF)-loaded electrospun poly(lactide-co-glycolide) (PLGA) fibrous membrane for repairing RCT. Implantable biodegradable bFGF-PLGA fibrous membranes were successfully fabricated using emulsion electrospinning technology and then characterized and evaluated with in vitro and in vivo cell proliferation assays and repairs of rat chronic RCTs. Emulsion electrospinning fabricated ultrafine fibers with a core-sheath structure which secured the bioactivity of bFGF in a sustained manner for 3 weeks. Histological observations showed that electrospun fibrous membranes have excellent biocompatibility and biodegradability. At 2, 4, and 8 weeks after in vivo RCT repair surgery, electrospun fibrous membranes significantly increased the area of glycosaminoglycan staining at the tendon-bone interface compared with the control group, and bFGF-PLGA significantly improved collagen organization, as measured by birefringence under polarized light at the healing enthesis compared with the control and PLGA groups. Biomechanical testing showed that the electrospun fibrous membrane groups had a greater ultimate load-to-failure and stiffness than the control group at 4 and 8 weeks. The bFGF-PLGA membranes had the highest ultimate load-to-failure, stiffness, and stress of the healing enthesis, and their superiority compared to PLGA alone was significant. These results demonstrated that electrospun fibrous membranes aid in cell attachment and proliferation, as well as accelerating tendon-bone remodeling, and bFGF-loaded PLGA fibrous membranes have a more pronounced effect on tendon-bone healing. Therefore, augmentation using bFGF-PLGA electrospun fibrous membranes is a promising treatment for RCT.

Medial patellofemoral ligament reconstruction using semitendinosus tendons: polyester suture augmentation versus nonaugmentation.

BACKGROUND: The comparative clinical outcome of medial patellofemoral ligament reconstruction (MPFLR) using semitendinosus tendons with and without polyester suture augmentation for recurrent patellar instability is unknown. HYPOTHESIS: Medial patellofemoral ligament reconstruction with polyester suture augmentation will yield better results than MPFLR without augmentation for recurrent patellar instability in adults. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: One hundred patients with recurrent patellar instability receiving MPFLR using semitendinosus tendons were randomly divided into 2 groups either with or without polyester suture augmentation. Tibial tubercle transfer was performed in most cases. Follow-ups were performed at 12, 24, and 60 months postoperatively, and computed tomography (CT) was performed immediately after the operation and at follow-up. The passive patellar glide test was performed before surgery, immediately after MPFLR during the operation, and at each follow-up point. The degree of knee function was evaluated preoperatively and at 2 and 5 years postoperatively using the International Knee Documentation Committee, Lysholm, and Kujala rating scales. Redislocation or multiple episodes of patellar instability were considered failures. RESULTS: Forty-two patients in the augmentation group and 43 patients in the nonaugmentation group were followed for 5 years and received complete serial CT examinations and functional evaluations. The correction of the static patellar position deteriorated over time in the nonaugmentation group but not in the augmentation group. The results of the passive patellar glide test indicated stable patellae in all patients immediately after MPFLR and more stable patellae in the augmentation group at each follow-up point. Functional evaluations at 2 and 5 years revealed statistically significant superior results in the augmentation group. Finally, no patient in the augmentation group and 2 (4.7%) in the nonaugmentation group experienced episodes of redislocation, and 1 patient (2.4%) in the augmentation group and 8 (18.6%) in the nonaugmentation group experienced multiple episodes of patellar instability, resulting in failure rates of 2.4% and 23.3% in the augmentation group and nonaugmentation group, respectively (P = .004). CONCLUSION: Medial patellofemoral ligament reconstruction with polyester suture augmentation results in better static patellar position, dynamic stability, and functional outcome than without augmentation in the treatment of recurrent patellar dislocation in adults.