Tendon-bone Interface Research Articles

Rotator cuff healing is regulated by the lymphatic vasculature.

BackgroundDespite great advances in surgical techniques for rotator cuff tear (RCT) over the past decades, the postoperative failure rate of RCT is still high due to the poor healing competence of bone-tendon interface (BTI). The lymphatic vasculature plays a regulatory role in inflammatory disease and affects tissue healing. However, whether lymphangiogenesis and the role of lymphatic vasculature in the physiopathological process of rotator cuff （RC）injury remains unknown.MethodsIn this study, we constructed a mouse RC injury model and the BTI samples were collected for measurement. Firstly, immunofluorescence was used to investigate the temporal and spatial distribution of lymphangiogenesis in BTI area at different post-injury time points. Subsequently, the mice of experimental group were gavaged with the lymphatic inhibitors (SAR131675) on the first postoperative day to inhibit lymphangiogenesis, while the control group was treated with the vehicle. At postoperative week 2 and 4, the samples were collected for immunofluorescence staining to evaluate lymphatic angiogenesis inhibition. At postoperative week 4 and 8, The supraspinatus (SS) tendon–humeral complexes were collected for bone morphometric, histological and biomechanical tests to assess the healing outcome of the BTI.ResultsImmunofluorescence results showed that the lymphatic proliferation in the BTI injury area and increased in consistence with the healing time, and the lymphatic hyperplasia area significantly diminished at postoperative week 4. The lymphatic hyperplasia area in the SAR group was significantly lower than that in the control group both at 2 and 4 weeks postoperatively. Moreover, the administration of SAR131675 significantly impeded RC healing, as evidenced by lower histological scores, lower bone morphometric parameters, and worse biomechanical properties in comparison with that in control group at postoperative weeks 4 and 8.ConclusionLymphangiogenesis plays a positive role in RC healing, and targeting the lymphatic drainage at healing site may be a new therapeutic approach to promote RC injury repair.The translational potential of this articleThis is the first study to assess the specific role of lymphatic vessels in RC healing, and improving lymphatic drainage may be a potential new therapeutic approach to facilitate repair of BTI. Further, our study provides a reference for possible future treatment of BTI by intervening the lymphatic system.

Role of low-intensity pulsed ultrasound in regulating macrophage polarization to accelerate tendon-bone interface repair.

Low-intensity pulsed ultrasound (LIPUS) has been proven to accelerate the healing of the tendon-bone interface (TBI), and macrophages are considered to play an important regulatory role. This study was designed to explore the polarization of macrophages during treatment of TBI injury with LIPUS. In a rat model of rotator cuff tear, LIPUS or mock sonication (controls) was administered from 1 week postoperatively. The supraspinatus-supraspinatus tendon-humerus complexes were harvested for further evaluation at different time points for measures such as new bone formation, TBI maturity, ultimate failure load and stiffness, and types of macrophages. In vitro, bone marrow-derived macrophageswere cultured, and polarization was identified after stimulation with or without LIPUS (the LIPUS or control groups, respectively). Two weeks posttreatment, the LIPUS group showed higher bone volume/total volume ratios and better TBI maturity scores. Six weeks posttreatment, the failure load of the LIPUS group was significantly higher than that of the control group. LIPUS also accelerated initial inflammatory macrophage accumulation and facilitated anti-inflammatory macrophage polarization (M2) in the late period. In the in vitro macrophage polarization model, the LIPUS group showed a higher proportion of M2 macrophages and mRNA expression of anti-inflammatory genes than the control group, while there was no significant difference in the proinflammatory macrophages between the two groups. Our observations revealed that macrophage polarization may be a potential mechanism of LIPUS treatment for TBI repair.

Topographical and Compositional Gradient Tubular Scaffold for Bone to Tendon Interface Regeneration

The enthesis is an extremely specific region, localized at the tendon–bone interface (TBI) and made of a hybrid connection of fibrocartilage with minerals. The direct type of enthesis tissue is commonly subjected to full laceration, due to the stiffness gradient between the soft tissues and hard bone, and this often reoccurs after surgical reconstruction. For this purpose, the present work aimed to design and develop a tubular scaffold based on pullulan (PU) and chitosan (CH) and intended to enhance enthesis repair. The scaffold was designed with a topographical gradient of nanofibers, from random to aligned, and hydroxyapatite (HAP) nanoparticles along the tubular length. In particular, one part of the tubular scaffold was characterized by a structure similar to bone hard tissue, with a random mineralized fiber arrangement; while the other part was characterized by aligned fibers, without HAP doping. The tubular shape of the scaffold was also designed to be extemporarily loaded with chondroitin sulfate (CS), a glycosaminoglycan effective in wound healing, before the surgery. Micro CT analysis revealed that the scaffold was characterized by a continuous gradient, without interruptions from one end to the other. The gradient of the fiber arrangement was observed using SEM analysis, and it was still possible to observe the gradient when the scaffold had been hydrated for 6 days. In vitro studies demonstrated that human adipose stem cells (hASC) were able to grow and differentiate onto the scaffold, expressing the typical ECM production for tendon in the aligned zone, or bone tissue in the random mineralized part. CS resulted in a synergistic effect, favoring cell adhesion/proliferation on the scaffold surface. These results suggest that this tubular scaffold loaded with CS could be a powerful tool to support enthesis repair upon surgery.

Mechanical consequences at the tendon-bone interface of different medial row knotless configurations and lateral row tension in a simulated rotator cuff repair

PurposeLittle is known about the direct influence of different technical options at the rotator cuff tendon-bone interface (TBI) and, more specifically, at the medial bearing row (MBR), regarding local contact force, area and pressure. We evaluated the mechanical repercussions of different medial row anchor configurations for that setting using different values of tension in the lateral row anchors.MethodsKnotless transosseous equivalent (TOE) rotator cuff repairs with locked versus nonlocked medial anchors and single versus double-hole suture passage were tested in a synthetic rotator cuff mechanical model, using 2 different values of lateral row tension. Contact force, area, pressure, peak force and MBR force were compared at the simulated TBI using a pressure mapping sensor.ResultsWhen compared to locked anchors, medial row sliding configurations generate lower values for all the above-mentioned parameters.The use of double-hole suture passage in the medial cuff generated slightly higher values contact area regardless of lateral row tension. At higher lateral row tension values, lower values of the remaining parameters, including MBR force, were found when compared to single-hole suture passage.Lateral row anchor tension increase induced an increase of all parameters regardless of the medial row configuration and TBI contact force and MBR force were the most susceptible parameters, regardless of the medial row pattern.ConclusionMedial row mechanism, suture configuration and lateral row tension interfere with the mechanical force, area and pressure at by TBI. Lateral row tension increase is a major influencer in those parameters.These results can help surgeons choose the right technique considering its mechanical effect at the TBI.

Comparison of Healing Effect Between Fibrin Gel Complex Bone Morphological Protein and Reconstituted Bone Xenograft After Reconstruction of Sports Ligament Injury

To study the effect of fibrin gel complex bone morphological protein (FG-BMP) and RBX on the healing of tendon-bone interface. 51 live rabbits were selected, and 51 rabbits were randomly divided into 3 groups: FG-BMP, RBX and control groups. Bilateral ACL reconstruction was performed in 51 rabbits, with different biomaterials injected at the tendon-bone interface, and none applied in the FG-BMP, RBX, and control groups. Material extraction, imaging examination, histological analysis, and biomechanical tests were conducted at 2 weeks after surgery, 6 weeks later, and 12 weeks after surgery, respectively. The tendon-interbone growth rate of rabbits using FG-BMP biomaterials and RBX biomaterials was significantly improved in the FG-BMP and RBX groups compared with the control group (P < 0.05). Histological results showed that all rabbits in the RBX group were surrounded by newborn bone tissue around the tendon-bone transplantation tendon and had a significantly greater number of newborn bone tissue than in the FG-BMP group (P < 0.05). The biomechanical test results showed that the two groups of FG-BMP biomaterials improved the maximum tension compared with the control group (P < 0.05), where the RBX tension, the difference was significant (P < 0.05), and the FG-BMP group although higher than the control group (P > 0.05). Conclusion: In the comparison of promoting tendon-bone interface healing, FG-BMP biomaterials and RBX biomaterials have significant results, especially RBX materials have obvious advantages in accelerating tendon-bone interface healing.

BMSC-derived exosomes promote tendon-bone healing after anterior cruciate ligament reconstruction by regulating M1/M2 macrophage polarization in rats

BackgroundRecent studies have shown that bone marrow stromal cell-derived exosomes (BMSC-Exos) can be used for tissue repair. However, whether the BMSC-Exos can promote tendon-bone healing after anterior cruciate ligament reconstruction (ACLR) is still unclear. In this study, we observed in vivo and in vitro the effect of rat BMSC-Exos on tendon-bone healing after ACLR and its possible mechanism.MethodsHighly expressed miRNAs in rat BMSC-Exos were selected by bioinformatics and verified in vitro. The effect of overexpressed miRNA in BMSC-Exos on M2 macrophage polarization was observed. A rat model of ACLR was established. The experimental components were divided into three groups: the control group, the BMSC-Exos group, and the BMSC-Exos with miR-23a-3p overexpression (BMSC-Exos mimic) group. Biomechanical tests, micro-CT, and histological staining were performed for analysis.ResultsBioinformatics analysis showed that miR-23a-3p was highly expressed in rat BMSC-Exos and could target interferon regulatory factor 1 (IRF1, a crucial regulator in M1 macrophage polarization). In vitro, compared with the control group or the BMSC-Exos group, the BMSC-Exos mimic more significantly promoted the polarization of macrophages from M1 to M2. In vivo, at 2 weeks, the number of M2 macrophages in the early local stage of ACLR was significantly increased in the BMSC-Exos mimic group; at 4 and 8 weeks, compared with the control group or the BMSC-Exos group, the bone tunnels of the tibia and femur sides of the rats in the BMSC-Exos mimic group were significantly smaller, the interface between the graft and the bone was narrowed, the bone volume/total volume ratio (BV/TV) increased, the collagen type II alpha 1 level increased, and the mechanical strength increased.ConclusionsBMSC-Exos promoted M1 macrophage to M2 macrophage polarization via miR-23a-3p, reduced the early inflammatory reaction at the tendon-bone interface, and promoted early healing after ACLR.

3-in-1 Hybrid Suture Bridge Technique in Posterosuperior Rotator Cuff Tear

Our technique repaired the posterosuperior rotator cuff tear in the full-thickness type. The key successful of the arthroscopic full-thickness rotator cuff repair has several suture techniques. First, it will distribute a tensile force throughout the entire tendon. Second, it will improve tendon healing by getting it closer to the medial anatomical footprint. Third, the suture bridge compression technique has been used to compress all layers of the repaired tendon against the bone with the total contact area. Fourth, it reduces the risk of cut through the rotator cuff and the rate of rotator cuff retear with a tension free repair. We used three suture limbs in one hole to reduce rotator cuff damage and the rate of retear and also only tie three medial row knots. The reasons are to compress anatomically the medial footprint. The configuration suture pattern consists of suture bridges that distribute pressure-tension over a larger contact surface area on the tendon-bone interface, allowing for robust tendon-bone stabilization, better tendon-bone healing, and less retear after repair.

Rotator Cuff Repair With a Bioinductive Patch

Background: As a degenerative condition, symptomatic rotator cuff disease is frequently seen in the aging population, often requiring arthroscopic repair to eliminate pain and restore function. Repair integrity remains a concern in both short- and long-term postoperative periods due to high rates of primary repair failures, leading to increased interest in biologic patch augmentation to improve healing. Indications: Patch augmentation during rotator cuff repair is indicated in patients at high risk for repair failure or incomplete healing, including patients with poor quality, degenerative tendon tissue, those undergoing revision repair, and patients with large or massive rotator cuff tears. Technique Description: Standard arthroscopic portals are established and following diagnostic arthroscopy, the rotator cuff tear is identified, mobilized, and the humeral head gently debrided to a bleeding surface. Medial row suture anchors are placed, and following suture passage through the rotator cuff, the medial row sutures are tied. A bioinductive augmentation patch is introduced and provisionally secured medial to the enthesis utilizing spinal needles. Sutures are shuttled over the patch and incorporated into the lateral row repair utilizing 2 knotless suture anchors, effectively securing the patch over the bone-tendon interface. Results: Utilization of the described patch augmentation technique may improve repair healing by stimulating collagen formation and tissue vascularity, while providing structural support during the immediate postoperative period, effectively facilitating new tissue formation. Discussion/Conclusion: Incorporation of the bioinductive patch into the lateral row suture repair, directly over the tendon-bone interface, may assist in repair healing and decrease issues related to patch migration, while minimizing operative time and materials cost.

Poster 110: Depth of Tissue Necrosis Following Footprint Preparation with Arthroscopic Radiofrequency Ablation

Objectives:Successful rotator cuff repair depends upon both secure fixation and biologic integration at the bone-tendon interface. Viable osteocytes and sound bony architecture contribute to the mechanical stability of suture anchor repair constructs. Furthermore, because tendons are hypovascular, preserving the microvasculature of the underlying bone bed is important. To create the bone-tendon interface, shoulder surgeons typically employ three different techniques to clear soft tissue from the footprint prior to rotator cuff repair: mechanical debridement, radiofrequency coagulation, and radiofrequency ablation. Conventional radiofrequency devices use radiofrequency energy to vaporize tissue, often in the setting of tumor resection to kill cancerous tissue. In arthroscopy, bipolar radiofrequency wands capitalize on the saline environment, passing radiofrequency waves through the conductive saline medium creating high energy ions. The result is a plasma field that can gently dissolve tissue with limited heat penetration to the surrounding environment, which is referred to as “coblation.” However, the extent to which this energy penetrates the adjacent tissue, potentially damaging nearby vasculature and osteocytes, is unknown. This study aims to explore the histological depth of tissue necrosis caused by arthroscopic radiofrequency ablation wands in comparison to a mechanical shaver.Methods:6 bovine metacarpal bones were collected one hour after devascularization and submerged in normal saline. Footprints were created by a radiofrequency ablation wand, at both the coagulation and ablation settings, and a mechanical shaver. Preparation was performed at 5 and 15 seconds. After the specimens were processed and prepared as hematoxylin and eosin-stained microscopic slides, each footprint was evaluated microscopically by a fellowship-trained pathologist. Depth of tissue destruction, preservation of periosteum, and osteocyte necrosis were evaluated histologically compared to the control sections for each treatment method.Results:Both the coagulation and ablation settings on the radiofrequency ablation wand were compared to the sections debrided with the mechanical shaver and the control sections. The ablation setting removed significantly more tissue than the coagulation setting at 5 seconds and 15 seconds of energy exposure (0.67 mm vs. 2.3 mm; P = .001 and 1.5 mm vs. 3.58 mm; P = .012) (table 1). While the depth of soft tissue destruction increased with time, the difference between 5 and 15 seconds for either treatment was not significant (0.67 mm vs. 1.5 mm; P = ,088, 2.3 mm vs. 3.58 mm; P = .051). The periosteum was rarely breached by any treatment and was seen to be well preserved in most sections. Osteocytes remained viable in the central area of treatment, and the normal cortical bone architecture was maintained. Compared to the control bone sections (figure 1) there was one section treated with ablation for 15 seconds that showed complete loss of overlying soft tissue in the treatment area and necrotic osteocytes at a depth of 0.5 mm from the treatment area (figure 2, 3).Conclusions:When used appropriately, arthroscopic radiofrequency ablation techniques effectively debride soft tissue from the rotator cuff footprint while preserving the underlying periosteal vasculature and cortical osteocytes. However, our results do show that local tissue destruction increases with degree of radiofrequency energy and exposure time which can lead to necrosis of the underlying tissues including the periosteum, osteocytes, and microvasculature. This has the potential to impair the biologic tendon-to-bone healing as well as the integrity of the mechanical repair construct, which would ultimately lead to failure of the repair. Thus, it is important for surgeons to be cautious while using arthroscopic radiofrequency techniques while preparing tendon footprints.TABLE 1.Depth of Soft Tissue Destruction by Treatment in millimeters (mm)Figure 1.Control, 20X. Histologic section demonstrating normal- periosteum, bony architecture, and viable osteocytes. White arrow: intact periosteum. Black arrow: Viable osteocyte.Figure 2.Ablation 15 seconds, 10X. White arrow: intact periosteum. Black arrow: treatment area with complete loss of periosteumFigure 3.Ablation 15 seconds, 20X. Histologic section demonstrating necrotic osieocytes at a depth of 0.5 mm below the treatment area.j White arrow: zone of necrotic osteocytes. Black arrow: viable osteocyie

Poster 203: Mechanical Loading Effects on OA Progression Following ACL Injury and Reconstruction in a Murine Model: Radiographic Assessment of Synovial Fibroblast Activity

Poster 203: Mechanical Loading Effects on OA Progression Following ACL Injury and Reconstruction in a Murine Model: Radiographic Assessment of Synovial Fibroblast Activity

Effect of secretory leucocyte protease inhibitor on early tendon-to-bone healing after anterior cruciate ligament reconstruction in a rat model

AimsTo verify whether secretory leucocyte protease inhibitor (SLPI) can promote early tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction.MethodsIn vitro: the mobility of the rat bone mesenchymal stem cells (BMSCs) treated with SLPI was evaluated by scratch assay. Then the expression levels of osteogenic differentiation-related genes were analyzed by real-time quantitative PCR (qPCR) to determine the osteogenic effect of SLPI on BMSCs. In vivo: a rat model of ACL reconstruction was used to verify the effect of SLPI on tendon-to-bone healing. All the animals of the SLPI group and the negative control (NC) group were euthanized for histological evaluation, micro-CT scanning, and biomechanical testing.ResultsSLPI improved the migration ability of BMSCs and upregulated the expression of genes related to osteogenic differentiation of BMSCs in vitro. In vivo, the SLPI group had higher histological scores at the tendon-bone interface by histological evaluation. Micro-CT showed more new bone formation and bone ingrowth around the grafted tendon in the SLPI group. Evaluation of the healing strength of the tendon-bone connection showed that the SLPI group had a higher maximum failure force and stiffness.ConclusionSLPI can effectively promote early tendon-to-bone healing after ACL reconstruction via enhancing the migration and osteogenic differentiation of BMSCs.Cite this article: Bone Joint Res 2022;11(7):503–512.

Poster 130: Tendon-to-bone Healing in a CCR2 Knockout Mouse Model of Delayed Rotator Cuff Repair

Poster 130: Tendon-to-bone Healing in a CCR2 Knockout Mouse Model of Delayed Rotator Cuff Repair

Degradable magnesium alloy suture promotes fibrocartilaginous interface regeneration in a rat rotator cuff transosseous repair model

Despite transosseous rotator cuff tear repair using sutures is widely accepted for tendon-bone fixation, the fibrocartilaginous enthesis regeneration is still hardly achieved with the traditional sutures. In the present work, degradable magnesium (Mg) alloy wire was applied to suture supraspinatus tendon in a rat acute rotator cuff tear model with Vicryl Plus 4–0 absorbable suture as control. The shoulder joint humerus-supraspinatus tendon complex specimens were retrieved at 4, 8, and 12 weeks after operation. The Mg alloy suture groups showed better biomechanical properties in terms of ultimate load to failure. Gross observation showed that hyperplastic response of the scar tissue at the tendon-bone interface is progressively alleviated over time in the both Mg alloy suture and Vicryl suture groups. In the histological analysis, for Mg alloy suture groups, chondrocytes appear to proliferate at 4 weeks postoperatively, and the tendon-bone interface showed an orderly structural transition zone at 8 weeks postoperatively. The collagenous fiber tended to be aligned and the tendon-bone interlocking structures apparently formed, where transitional structure from unmineralized fibrocartilage to mineralized fibrocartilage was closer to the native fibrocartilaginous enthesis. In vivo degradation of the magnesium alloy wire was completed within 12 weeks. The results indicated that Mg alloy wire was promising as degradable suture with the potential to promotes fibrocartilaginous interface regeneration in rotator cuff repair.

Exosomes derived from magnetically actuated bone mesenchymal stem cells promote tendon-bone healing through the miR-21-5p/SMAD7 pathway.

Graft healing after anterior cruciate ligament reconstruction (ACLR) involves slow biological processes, and various types of biological modulations have been explored to promote tendon-to-bone integration. Exosomes have been extensively studied as a promising new cell-free strategy for tissue regeneration, but few studies have reported their potential in tendon-to-bone healing. In this study, a novel type of exosome derived from magnetically actuated (iron oxide nanoparticles (IONPs) combined with a magnetic field) bone mesenchymal stem cells (BMSCs) (IONP-Exos) was developed, and the primary purpose of this study was to determine whether IONP-Exos exert more significant effects on tendon-to-bone healing than normal BMSC-derived exosomes (BMSC-Exos). Here, we isolated and characterized the two types of exosomes, conducted in vitro experiments to measure their effects on fibroblasts (NIH3T3), and performed in vivo experiments to compare the effects on tendon-to-bone integration. Moreover, functional exploration of exosomal miRNAs was further performed by utilizing a series of gain- and loss-of-function experiments. Experimental results showed that both BMSC-Exos and IONP-Exos could be shuttled intercellularly into NIH3T3 fibroblasts and enhanced fibroblast activity, including proliferation, migration, and fibrogenesis. In vivo, we found that IONP-Exos significantly prevented peri-tunnel bone loss, promoted more osseous ingrowth into the tendon graft, increased fibrocartilage formation at the tendon-bone tunnel interface, and induced a higher maximum load to failure than BMSC-Exos. Furthermore, overexpression of miR-21-5p remarkably enhanced fibrogenesis in vitro, and SMAD7 was shown to be involved in the promotive effect of IONP-Exos on tendon-to-bone healing. Our findings may provide new insights into the regulatory roles of IONPs in IONP-Exos communication via stimulating exosomal miR-21-5p secretion and the SMAD7 signaling pathway in the fibrogenic process of tendon-to-bone integration. This work could provide a new strategy to promote tendon-to-bone healing for tissue engineering in the future.

Local Administration of Metformin Improves Bone Microarchitecture and Biomechanical Properties During Ruptured Canine Achilles Tendon–Calcaneus Interface Healing

Background: Tendon-bone interface (TBI) healing is a clinical dilemma that is closely relevant to new bone formation and remodeling at the repair site. Previous studies showed that metformin is an osteogenic inducer for stem cells in vitro and capable of stimulating bone regeneration in vivo. Hypothesis: Metformin would be effective for promoting TBI healing by enhancing new bone formation and remodeling. Study Design: Controlled laboratory study. Methods: Canine bone marrow stem cells (BMSCs) were cultured with various concentrations of metformin (0, 10, 50, 100, 200 μM). The effect of metformin on the osteogenic differentiation of canine BMSCs was evaluated via alizarin red staining and osteogenic gene expression. Eighteen mature beagles were included in a bilateral Achilles tendon–calcaneus (ATC) interface injury model. The right interface was reattached via surgical repair only, while the left was surgically reattached after implanting a fibrin glue containing metformin. At postoperative week 4 or 8, the healing quality of the wounded ATC interfaces was evaluated. Results: In vitro experiments determined that metformin was an osteogenic inducer for canine BMSCs. In vivo experiments showed that the metformin-treated ATC interfaces were repaired with significantly greater failure load and stiffness than was the no-metformin control site (P < .05 for all). Micro–computed tomography analysis showed that the metformin-treated specimens presented significantly higher bone volume/total volume and trabecular thickness than did the no-metformin control specimens (P < .05 for all), as confirmed via hematoxylin and eosin staining. Immunohistochemical staining showed that significantly more osteocalcin-positive cells were located at the newly formed bones treated with metformin than at the no-metformin control site at week 4 (P < .05). Masson trichrome staining showed that significantly more oriented collagen fibers anchored into the newly formed bone of the metformin-treated site than the no-metformin control site (P < .05). Conclusion: Metformin induced the osteogenesis of canine BMSCs in vitro, and local administration of metformin provided an improvement of bone microarchitecture at the calcaneus as well as an increase in the tensile properties of the repaired ATC interfaces in canines. Clinical Relevance: Findings of the study indicate that local administration of metformin may be an effective strategy for TBI healing in clinic.

Biomechanical Evaluation of 2 Common Approaches for Total Elbow Arthroplasty: Triceps Tongue Compared With Triceps Reflecting

We hypothesize that the triceps tongue approach will be equivalent in strength to the triceps reflecting approach in load to failure following a cyclic preload. Seven paired fresh-frozen cadaveric arms were dissected using the triceps reflecting approach or triceps tongue approach to the posterior elbow. The triceps was then repaired in each specimen, and the elbows were placed in a testing jig. Elbows were preloaded in a cyclic fashion at 5 lbs (2.3 kgf) for 200 cycles in flexion/extension, followed by load to failure. The stiffness and ultimate failure strength for each specimen were determined. We defined ultimate failure as gapping in the suture construct of 4 mm or suture breakage. One of the triceps tongue specimens was excluded due to a testing error, resulting in 6 elbows in this group. There were no tendon repair failures during the cyclic preload. The median ultimate failure of the reflecting group occurred at 65 pounds, compared to 115 pounds in the tongue group. This was significantly different. The reflecting approach consistently failed along the entire bone-tendon interface. The tongue approach failed at the proximal repair site in 4 of 6 specimens, while the longitudinal aspect of the tendon repair remained intact. Following a cyclic preload of 5 lbs for 200 cycles, the triceps tongue repair is stronger than triceps reflecting in ultimate failure. The mode of failure of triceps tongue repair may be superior to that of triceps reflecting. This study may help guide surgeons when choosing a "triceps off" approach to total elbow arthroplasty.

Nano-calcium silicate mineralized fish scale scaffolds for enhancing tendon-bone healing.

Tendon-bone healing is essential for an effective rotator cuff tendon repair surgery, however, this remains a significant challenge due to the lack of biomaterials with high strength and bioactivity. Inspired by the high-performance exoskeleton of natural organisms, we set out to apply natural fish scale (FS) modified by calcium silicate nanoparticles (CS NPs) as a new biomaterial (CS-FS) to overcome the challenge. Benefit from its “Bouligand” microstructure, such FS-based scaffold maintained excellent tensile strength (125.05 MPa) and toughness (14.16 MJ/m3), which are 1.93 and 2.72 times that of natural tendon respectively, allowing it to well meet the requirements for rotator cuff tendon repair. Additionally, CS-FS showed diverse bioactivities by stimulating the differentiation and phenotypic maintenance of multiple types of cells participated into the composition of tendon-bone junction, (e.g. bone marrow mesenchymal stem cells (BMSCs), chondrocyte, and tendon stem/progenitor cells (TSPCs)). In both rat and rabbit rotator cuff tear (RCT) models, CS-FS played a key role in the tendon-bone interface regeneration and biomechanical function, which may be achieved by activating BMP-2/Smad/Runx2 pathway in BMSCs. Therefore, natural fish scale -based biomaterials are the promising candidate for clinical tendon repair due to their outstanding strength and bioactivity.

Canine ACL reconstruction with an injectable hydroxyapatite/collagen paste for accelerated healing of tendon-bone interface.

Healing of an anterior cruciate ligament (ACL) autologous graft in a bone tunnel occurs through the formation of fibrovascular scar tissue, which is structurally and compositionally inferior to normal fibrocartilaginous insertion and thus may increase the reconstruction failure and the rate of failure recurrence. In this study, an injectable hydroxyapatite/type I collagen (HAp/Col Ⅰ) paste was developed to construct a suitable local microenvironment to accelerate the healing of bone-tendon interface. Physicochemical characterization demonstrated that the HAp/Col Ⅰ paste was injectable, uniform and stable. The in vitro cell culture illustrated that the paste could promote MC3T3-E1 cells proliferation and osteogenic expression. The results of a canine ACL reconstruction study showed that the reconstructive ACL had similar texture and color as the native ACL. The average width of the tunnel, total bone volume, bone volume/tissue volume and trabecular number acquired from micro-CT analysis suggested that the healing of tendon-bone interface in experimental group was better than that in control group. The biomechanical test showed the maximal loads in experimental group achieved approximately half of native ACL's maximal load at 24 weeks. According to histological examination, Sharpey fibers could be observed as early as 12 weeks postoperatively while a typical four-layer transitional structure of insertion site was regenerated at 48 weeks in the experimental group. The injectable HAp/Col Ⅰ paste provided a biomimetic scaffold and microenvironment for early cell attachment and proliferation, further osteogenic expression and extracellular matrix deposition, and in vivo structural and functional regeneration of the tendon-bone interface.

Upregulation of Runt related transcription factor 1 (RUNX1) contributes to tendon–bone healing after anterior cruciate ligament reconstruction using bone mesenchymal stem cells

BackgroundAnterior cruciate ligament (ACL) injury could lead to functional impairment along with disabilities. ACL reconstruction often fails owing to the regeneration failure of tendon–bone interface. Herein, we aimed to investigate the effects of Runt related transcription factor 1 (RUNX1) on tendon–bone healing after ACL reconstruction using bone mesenchymal stem cells (BMSCs).MethodsBMSCs were isolated from the marrow cavity of rat femur, followed by the modification of RUNX1 with lentiviral system. Then, an ACL reconstruction model of rats was established with autografts.ResultsResults of flow cytometry exhibited positive-antigen CD44 and CD90, as well as negative-antigen CD34 and CD45 of the BMSCs. Then, we found that RUNX1-upregulated BMSCs elevated the decreased biomechanical strength of the tendon grafts after ACL reconstruction. Moreover, based on the histological observation, upregulation of RUNX1 was linked with better recovery around the bone tunnel, a tighter tendon–bone interface, and more collagen fibers compared to the group of BMSCs infected with LV-NC. Next, RUNX1-upregulated BMSCs promoted osteogenesis after ACL reconstruction, as evidenced by the mitigation of severe loss and erosion of the cartilage and bone in the tibial and femur area, as well as the increased number of osteoblasts identified by the upregulation of alkaline phosphatase, osteocalcin, and osteopontin in the tendon–bone interface.ConclusionElevated expression of RUNX1 contributed to tendon–bone healing after ACL reconstruction using BMSCs.

3D cell-printing of gradient multi-tissue interfaces for rotator cuff regeneration.

Owing to the prevalence of rotator cuff (RC) injuries and suboptimal healing outcome, rapid and functional regeneration of the tendon–bone interface (TBI) after RC repair continues to be a major clinical challenge. Given the essential role of the RC in shoulder movement, the engineering of biomimetic multi-tissue constructs presents an opportunity for complex TBI reconstruction after RC repair. Here, we propose a gradient cell-laden multi-tissue construct combined with compositional gradient TBI-specific bioinks via 3D cell-printing technology. In vitro studies demonstrated the capability of a gradient scaffold system in zone-specific inducibility and multi-tissue formation mimicking TBI. The regenerative performance of the gradient scaffold on RC regeneration was determined using a rat RC repair model. In particular, we adopted nondestructive, consecutive, and tissue-targeted near-infrared fluorescence imaging to visualize the direct anatomical change and the intricate RC regeneration progression in real time in vivo. Furthermore, the 3D cell-printed implant promotes effective restoration of shoulder locomotion function and accelerates TBI healing in vivo. In summary, this study identifies the therapeutic contribution of cell-printed constructs towards functional RC regeneration, demonstrating the translational potential of biomimetic gradient constructs for the clinical repair of multi-tissue interfaces.