Background: Exosomes derived from mesenchymal stromal cells (MSCs) reportedly enhance the healing process. However, no studies have investigated the effect of exosomes from infrapatellar fat pad (IPFP) MSCs on tendon-bone healing and intra-articular graft remodeling after anterior cruciate ligament reconstruction (ACLR). Purpose: To evaluate the in vivo effect of exosomes from IPFP MSCs on tendon-bone healing and intra-articular graft remodeling in a rat model of ACLR. Study Design: Controlled laboratory study. Methods: A total of 90 skeletally mature male Sprague Dawley rats underwent unilateral ACLR using an autograft. All rats were randomly divided into 3 groups: sham injection (SI) group (n = 30), control injection (CI) group (n = 30), and IPFP MSC–derived exosome injection (IMEI) group (n = 30). At 2, 4, and 8 weeks postoperatively, tendon-bone healing and intra-articular graft remodeling were evaluated via biomechanical testing, micro–computed tomography, and histological analysis; macrophage polarization was evaluated using immunohistochemical staining. Results: Biomechanical testing demonstrated a significantly higher failure load and stiffness in the IMEI group than in the SI and CI groups at 4 and 8 weeks postoperatively. Moreover, a thinner graft-to-bone healing interface with more fibrocartilage was observed in the IMEI group at both time points. Micro–computed tomography revealed greater new bone ingrowth in the IMEI group than in the other groups, as demonstrated by smaller mean bone tunnel areas and a larger bone volume/total volume ratio. Additionally, more cellular infiltration was observed in the intra-articular graft in the IMEI group than in the other groups at 4 weeks, followed by more regularly organized fibers with mature collagen at 8 weeks. Notably, similar trends of macrophage polarization were found at both the graft-to-bone interface and the intra-articular graft in the IMEI group, with significantly fewer proinflammatory M1 macrophages and larger numbers of reparative M2 macrophages than in the SI and CI groups. Conclusion: IPFP MSC–derived exosomes accelerated tendon-bone healing and intra-articular graft remodeling after ACLR, which may have resulted from the immunomodulation of macrophage polarization. Clinical Relevance: The IPFP can be easily harvested by most orthopaedic surgeons. Exosomes from IPFP MSCs, constituting a newly emerging cell-free approach, may represent a treatment option for improving tendon-bone healing and intra-articular graft remodeling after ACLR.

Glucocorticoid (GC) injections are commonly used in clinical practice to relieve pain and improve function in patients with multiple shoulder disabilities but cause detrimental effects on rotator cuff tendons. Adipose stem cell-derived exosomes (ASC-Exos) reportedly recover impaired tendon matrix metabolism by maintaining tissue homeostasis. However, it is unclear whether additional treatment with ASC-Exos overrides the detrimental effects of GCs without interfering with their anti-inflammatory effects. Thus, we aimed to investigate the anti-inflammatory effect of ASC-Exos with GCs and protective effect of ASC-Exos against GC-induced detriments. The present study comprised in vitro and in vivo studies. In vitro inflammatory analysis revealed that ASC-Exos exerted a synergic anti-inflammatory effect with GCs by significantly decreasing secretion of proinflammatory cytokines by RAW cells and increasing secretion of anti-inflammatory cytokines. In vitro cytoprotective analysis showed that ASC-Exos overrode GC-induced detrimental effects on tenocytes by significantly improving GC-suppressed cellular proliferation, migration, and transcription of tenocytic matrix molecules and degradative enzyme inhibitors and significantly decreasing GC-induced cell senescence, apoptosis, and transcription of ROS and tenocytic degradative enzymes. In vivo studies revealed that additional ASC-Exo injection restored impairments in histological and biomechanical properties owing to GC administration. Collectively, these results suggest that ASC-Exos exert a stronger anti-inflammatory effect in combination with GCs, overriding their detrimental effects on rotator cuff tendons.

Background: Retraction and degenerative changes of chronic rotator cuff tears limit the healing capacity after routine surgical repair. Purpose: To fabricate a mesenchymal stem cell–derived exosome (MSC–Exos) loaded patch and evaluate the effect of this patch on the activity of rabbit tenocytes in vitro and on the repair of chronic rotator cuff tears associated with degenerative changes in vivo. Study Design: Controlled laboratory study. Methods: The MSC–Exos loaded patch was fabricated using a dynamic wet-spinning system. In the in vitro studies, the proliferation and migration activities of tenocytes were evaluated by culturing tenocytes with saline, a fiber-aligned patch, or an MSC–Exos loaded patch. In the in vivo studies, a rabbit model of chronic rotator cuff tear was established and directly repaired, repaired with fiber-aligned patch augmentation (RFPA group), and repaired with MSC–Exos loaded patch augmentation (REPA group). Histological and biomechanical analyses were performed at 4, 8, and 12 weeks after surgery. Results: An MSC–Exos loaded patch with inner aligned fibers, a loose microstructure, and reliable initial strength was fabricated using a dynamic wet-spinning system. The MSC–Exos loaded patch significantly promoted tenocyte proliferation and migration activities in vitro. In vivo, the REPA group exhibited significantly higher tendon maturing scores at 8 and 12 weeks after surgery compared with both the control and the RFPA groups. Fatty infiltration was significantly reduced in the REPA group at 4, 8, and 12 weeks compared with both the control and the RFPA groups. Biomechanical properties, including load to failure and stress, were also significantly improved at 12 weeks in the REPA group compared with both the control and the RFPA groups. Conclusion: Results in the present study suggested that an MSC–Exos loaded patch was able to enhance the repair of a chronic rotator cuff tear by providing mechanical support and minimizing degeneration. Clinical Relevance: This work supported the idea that loading bioactive MSC–Exos into a traditionally designed rotator cuff patch might exert a better effect on the repair of chronic rotator cuff tears than augmented patch repair alone.

Background: Medial patellofemoral ligament (MPFL) reconstruction is one of the main treatments for lateral patellar translation. Based on intraoperative true lateral radiographs, the accepted methods for femoral MPFL tunnel location are potentially inaccurate. Direct assessment of anatomic characteristics during surgery through palpation of the anatomic landmarks involving the saddle sulcus might help eliminate tunnel malposition. Hypothesis: The saddle sulcus is a reliable osseous landmark where the MPFL attaches for tunnel placement. Study Design: Descriptive laboratory study. Methods: A total of 9 fresh-frozen unpaired human cadaveric knees were dissected; MPFL insertion point and relative osseous structures were marked. Three-dimensional images and transformed true lateral radiographs were obtained for analysis; 3 previously reported radiographic reference points for MPFL femoral tunnel placement were determined on all images and compared with the anatomic insertion. Results: A saddle sulcus consistently existed where the MPFL was attached, located at 11.7 ± 5.9 mm from the apex of the adductor tubercle (AT) to the medial epicondyle (ME), 62.8% of the average distance between the apexes of the AT and ME, and 5.6 ± 2.8 mm perpendicular-posterior to the border connecting the AT and ME. The reported radiographic reference points were located at average distances of 6.2 ± 3.2 mm (Schöttle method), 5.9 ± 2.3 mm (Redfern method), and 7.3 ± 6.6 mm (Fujino method) from the saddle sulcus center on the true lateral radiographs. Conclusion: The saddle sulcus was a reliable landmark where the MPFL was anatomically attached, located approximately 12 mm from the AT to the ME (approximately 60% along a line from the AT to the ME) and 6 mm perpendicular-posterior to the border connecting the apexes of the AT and ME. Additionally, the saddle sulcus position presented variability on the femoral aspect of different knees. All of the average direct distances from the sulcus to the reference radiographic points exceeded 5 mm, and tunnel localizations on a true lateral radiograph were inaccurate. Clinical Relevance: This study demonstrates the potential precise position of the saddle sulcus, according to the ME and AT, as a reliable anatomic landmark for MPFL femoral tunnel location. Radiographic reference points were not accurate during MPFL reconstruction. Direct palpation of the landmarks might be effective for femoral MPFL tunnel placement.