Wang, Zhanwen

Background: Rotator cuff repair augmentation using biological materials has become popular in clinical practice to reduce the high retear rates associated with traditional repair techniques. Tissue engineering approaches, such as engineered tendon-fibrocartilage-bone composite (TFBC), have shown promise in enhancing the biological healing of rotator cuff tears in animals. However, previous studies have provided limited long-term data on TFBC repair outcomes. The effect of mechanical stimulation on TFBC has not been explored extensively. Purpose: To evaluate functional outcomes after rotator cuff repair with engineered TFBC subjected to mechanical stimulation in a 6-month follow-up using a canine in vivo model. Study Design: Controlled laboratory study. Methods: A total of 40 canines with an acute infraspinatus (ISP) tendon transection model were randomly allocated to 4 groups (n =10): (1) unilateral ISP tendon undergoing suture repair only (control surgery); (2) augmentation with engineered TFBC alone (TFBC); (3) augmentation with engineered TFBC and bone marrow-derived stem cells (BMSCs) (TFBC+C); and (4) augmentation with engineered TFBC and BMSCs, as well as mechanical stimulation (TFBC+C+M). Outcome measures—including biomechanical evaluations such as failure strength, stiffness, failure mode, gross appearance, ISP tendon and muscle morphological assessment, and histological analysis—were performed 6 months after surgery. Results: As shown in the mechanical test, the TFBC+C+M group exhibited higher failure strength compared with other repair techniques. The most common failure mode was avulsion fracture in the TFBC+C+M group, but tendon-bone junction rupture was observed predominantly in different groups. Engineered TFBC with mechanical stimulation showed over 70% relative failure strength compared with normal ISP, and the other groups showed about 50% relative failure strength. Histological analysis revealed less fat infiltration and closer-to-normal muscle fiber structure in the mechanical stimulation group. Conclusion: This study provides evidence that mechanical stimulation of engineered TFBC promotes rotator cuff regeneration, thus supporting its potential for rotator cuff repair augmentation. Clinical Relevance: This study provides valuable evidence supporting the use of a novel tissue-engineered material (TFBC) in rotator cuff repair and paves the way for advancements in the field of rotator cuff regeneration.

AbstractThis study aimed to compare the clinically established autologous extrasynovial tendon graft to a newly developed tissue‐engineered allograft (Eng‐allograft) in terms of functional outcomes following flexor tendon reconstruction in a canine model. The second and fifth flexor digitorum profundus (FDP) tendons from 16 dogs were transected and repaired in Zone II. After 6 weeks of cage activity, the repaired tendons were intentionally ruptured, creating a clinically relevant model for reconstruction. The re‐ruptured FDP tendons were then reconstructed using either the clinically standard autologous extrasynovial tendon graft or the Eng‐allograft, which had been revitalized with autologous bone marrow‐derived mesenchymal stem cells (BMSCs) and synovialized using carbodiimide derivatized synovial fluid (cd‐SYN). Following 12 weeks of postoperative rehabilitation, the functional outcomes of the surgical digits were evaluated. The Eng‐allograft group exhibited improved digital function, including lower digit work of flexion and reduced adhesion status, while maintaining similar tendon gliding resistance compared to the autograft group. However, the failure load of both the distal and proximal host/graft conjunctions in the Eng‐allograft group was significantly lower than that of the autograft group with higher graft rupture at the host−graft junction. In conclusion, the decellularized allogenic intrasynovial tendon, when revitalized BMSCs and synovialized with cd‐SYN, demonstrates positive effects on digital function improvement and adhesion reduction. However, the healing at both proximal and distal graft/host junctions is far lower than the autograft. Further research is needed to enhance the healing capacity of allograft conjunctions, aiming to achieve a comparable level of healing seen with autografts.

Abstract Rotator cuff injuries increase with age. The enthesis is the most frequent site of rotator cuff injury and degeneration. Understanding age‐related changes of the enthesis are essential to determine the mechanism of rotator cuff injuries, degeneration, and to guide mechanistically driven therapies. In this study, we explored age‐related cellular changes of the rotator cuff enthesis in young, mature, and aged rats. Here we found that the aged enthesis is typified by an increased mineralized zone and decreased nonmineralized zone. Proliferation, migration, and colony‐forming potential of rotator cuff derived cells (RCECs) was attenuated with aging. The tenogenic and chondrogenic potential were significantly reduced, while the osteogenic potential increased in aged RCECs. The adipogenic potential increased in RCECs with age. This study explores the cellular differences found between young, mature, and aged rotator cuff enthesis cells and highlights the importance of using age‐appropriate models, as well as provides a basis for further delineation of mechanisms and potential therapeutics for rotator cuff injuries.

AbstractReducing tendon failure after repair remains a challenge due to its poor intrinsic healing ability. The purpose of this study is to investigate the effect of a novel tissue‐engineered purified exosome product (PEP) patch on tendon healing in a canine ex vivo model. Lacerated flexor digitorum profundus (FDP) tendons from three canines' paws underwent simulated repair with Tisseel patch alone or biopotentiated with PEP. For the ex vivo model, FDP tendons were randomly divided into three groups: FDP tendon repair alone group (Control), Tisseel patch alone group, and the Tisseel plus PEP (TEPEP) patch group. Following 4 weeks of tissue culture, the failure load, stiffness, histology, and gene expression of the healing tendon were evaluated. Transmission electron microscopy revealed that in exosomes of PEP the diameters ranged from 93.70 to 124.65 nm, and the patch release test showed this TEPEP patch could stably release the extracellular vesicle over 2 weeks. The failure strength of the tendon in the TEPEP patch group was significantly higher than that of the Control group and Tisseel alone group. The results of histology showed that the TEPEP patch group had the smallest healing gap and the largest number of fibroblasts on the surface of the injured tendon. Quantitative reverse transcription polymerase chain reaction showed that TEPEP patch increased the expression of collagen type III, matrix metallopeptidase 2 (MMP2), MMP3, MMP14, and reduced the expression of transforming growth factor β1, interleukin 6. This study shows that the TEPEP patch could promote tendon repair by reducing gap formation and inflammatory response, increasing the activity of endogenous cells, and formation of type III collagen.

Background: The retear rate after rotator cuff repair remains unacceptably high. Various biological engineered scaffolds have been proposed to reduce the retear rate. We have developed a double rip-stop repair with medial row knot (DRSK) technique to enhance suture-tendon strength and a novel engineered tendon-fibrocartilage-bone composite (TFBC) for rotator cuff repair. Hypothesis: DRSK rotator cuff repair augmented with TFBC will have better biomechanical properties than that of DRSK repair with an acellular dermal graft (DG). Study Design: Controlled laboratory study. Methods: Fresh-frozen canine shoulders (n = 30) and knees (n = 10) were used. TFBCs were harvested from the patellar tendon–tibia complex and prepared for rotator cuff repair. The infraspinatus tendon was sharply detached from its bony attachment and randomly assigned to the (1) control group: DRSK repair alone, (2) TFBC group: DRSK repair with TFBC, and (3) DG group: DRSK repair with DG. All specimens were tested to failure, and videos were recorded. The footprint area, tendon thickness, load to create 3-mm gap formation, failure load, failure modes, and stiffness were recorded and compared. Data were recorded as mean ± SD. Results: The mean load to create a 3-mm gap in both the control group (206.8 ± 55.7 N) and TFBC group (208.9 ± 39.1 N) was significantly higher than that in the DG group (157.7 ± 52.3 N) ( P < .05 for all). The failure load of the control group (275.7 ± 75.0 N) and TFBC group (275.2 ± 52.5 N) was significantly higher compared with the DG group (201.5 ± 49.7 N) ( P < .05 for both comparisons). The stiffness of the control group (26.4 ± 4.7 N/mm) was significantly higher than of the TFBC group (20.4 ± 4.4 N/mm) and the DG group (21.1 ± 4.8 N/mm) ( P < .05 for both comparisons). Conclusion: TFBC augmentation showed superior biomechanical performance to DG augmentation in rotator cuff tears repaired using the DRSK technique, while there was no difference between the TFBC and control groups. Clinical Relevance: TFBC may help to reduce retear or gap formation after rotator cuff repair using the DRSK technique.

AimsMany biomechanical studies have shown that the weakest biomechanical point of a rotator cuff repair is the suture-tendon interface at the medial row. We developed a novel double rip-stop (DRS) technique to enhance the strength at the medial row for rotator cuff repair. The objective of this study was to evaluate the biomechanical properties of the DRS technique with the conventional suture-bridge (SB) technique and to evaluate the biomechanical performance of the DRS technique with medial row knots.MethodsA total of 24 fresh-frozen porcine shoulders were used. The infraspinatus tendons were sharply dissected and randomly repaired by one of three techniques: SB repair (SB group), DRS repair (DRS group), and DRS with medial row knots repair (DRSK group). Specimens were tested to failure. In addition, 3 mm gap formation was measured and ultimate failure load, stiffness, and failure modes were recorded.ResultsThe mean load to create a 3 mm gap formation in the DRSK and DRS groups was significantly higher than in the SB group. The DRSK group had the highest load to failure with a mean ultimate failure load of 395.0 N (SD 56.8) compared to the SB and DRS groups, which recorded 147.1 N (SD 34.3) and 285.9 N (SD 89.8), respectively (p < 0.001 for both). The DRS group showed a significantly higher mean failure load than the SB group (p = 0.006). Both the DRS and DRSK groups showed significantly higher mean stiffness than the SB group.ConclusionThe biomechanical properties of the DRS technique were significantly improved compared to the SB technique. The DRS technique with medial row knots showed superior biomechanical performance than the DRS technique alone.