Tendon-bone Healing Research Articles

External stimulation: A potential therapeutic strategy for tendon-bone healing.

Injuries at the tendon-bone interface are very common in the field of sports medicine, and healing at the tendon-bone interface is complex. Injuries to the tendon-bone interface can seriously affect a patient's quality of life, so it is essential to restore stability and promote healing of the tendon-bone interface. In addition to surgical treatment, the healing of tendons and bones can also be properly combined with extracorporeal stimulation therapy during the recovery process. In this review, we discuss the effects of extracorporeal shock waves (ESWs), low-intensity pulsed ultrasound (LIPUS), and mechanical stress on tendon-bone healing, focusing on the possible mechanisms of action of mechanical stress on tendon-bone healing in terms of transcription factors and biomolecules. The aim is to provide possible therapeutic approaches for subsequent clinical treatment.

Outcome of intraoperative injection of collagen in arthroscopic repair of full-thickness rotator cuff tear: a retrospective cohort study

Rotator cuff (RC) pathologies are considered the most common cause of shoulder disability and pain. Arthroscopic repair of RC tears has proven to be an effective operation. Nonhealing and retear remain significant clinical problems and a challenge to surgeons. In addition, the essential biological augment to enhance RC tendon-bone healing is still under research. The purpose of the study was to assess the safety and efficacy of injection of atelocollagen and acellular dermal matrix (ADM) allograft in arthroscopic repair of full-thickness RC tears. From January 2018 to March 2020, a total of 129 patients with full-thickness RC tear were treated by arthroscopic repair only (group 1, n=36, with a mean age=63.2 years), arthroscopic repair together with atelocollagen 1-mL injection (group 2, n=44, with a mean age=63 years), or RC tears together with ADM allograft 1-mL injection (group 3, n=49, with a mean age=64.6 years). They were prospectively studied. This study included patients with a repairable full-thickness tear of the supraspinatus tendon size <5 cm. We excluded patients with isolated tears of the subscapularis tendon, those with a previous shoulder surgery, and those who had any type of injection for less than 6 weeks. American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form score, Constant Shoulder score, visual analog scale pain score, and range of motion were evaluated preoperatively, at 3, 6, and 12 months of the postoperative period and the final follow-up. In addition, magnetic resonance imaging was performed at 2 months and 12 months postoperatively. The mean follow-up period was 20 months. All groups showed improvement in functional and pain score at the final follow-up; however, there is no superior outcome among the 3 groups (P>.05). After 2 months, the nonhealing rate was 11% (4 of 36) for group 1, 4% (2 of 44) for group 2, and 2% (1 of 49) for group 3 (P>.05). The retear rates after 12 months was 19.4% (7 of 36) for group 1, 13.6% (6 of 44) for group 2, and 20.4% (10 of 49) for group 3 (P>.05). Adverse events were not detected in any groups. Our study did not show superior clinical or radiologic outcomes of atelocollagen and ADM allograft injections in arthroscopic RC repair over 12 months of follow-up in comparison to the control group. However, adverse events related to atelocollagen and ADM allograft injection were not observed.

Postoperative Tunnel Widening, Elliptical Aperture Shape, and No Preservation of the Remnant Are Related to the Tendon Graft–Bone Tunnel Gap Formation at the Intra-Articular Aperture After Double-Bundle Anterior Cruciate Ligament Reconstruction

To examine the bone-tendon healing at the posterolateral (PL) femoral tunnel aperture by second-look arthroscopy after double-bundle anterior cruciate ligament reconstruction (ACLR), and assess the risk factors for impaired healing at the tendon-bone interface. A consecutive series of knees undergoing primary double-bundle ACLR using hamstring tendon autografts were enrolled in the study. The exclusion criteria were as follows: previous knee surgeries, concomitant ligamentous and osseous procedures, and a lack of second-look arthroscopy or postoperative computed tomography data for the analysis. Cases in which a gap was identified between the graft and tunnel aperture during the second-look arthroscopic examination were classified as the gap formation (GF) group. A multivariate logistic regression analysis was performed to assess the relationship between the GF and variables that may determine prognosis. A total of 54 knees that met the inclusion/exclusion criteria were included in the study. Second-look arthroscopy revealed the GF at the PL aperture in 22 of the 54 knees (40%). The time period from surgery to arthroscopy averaged 16 months. In the multivariate logistic regression analysis, the percentage tunnel widening at 1 year on computed tomography (odds ratio, 10.4; 95% confidence interval [CI] 1.56-69.2), ellipticity of the tunnel aperture (odds ratio, 3.57; 95% CI, 0.79-16.11), and no ACL remnant preservation (odds ratio, 5.99; 95% CI, 1.23-29.06) were identified as prognostic factors significantly related to graft-bone tunnel GF. Second-look arthroscopy revealed GF at the PL graft-bone tunnel interface in 40% of the knees after double-bundle ACLR. Incomplete healing of the interface, as evidenced by a graft-bone gap at the tunnel aperture, was associated with tunnel widening 1-year postsurgery, an elliptical aperture shape, and no preservation of the ACL remnant. Ⅲ, retrospective case-control study.

Caveolin-1 is involved in fatty infiltration and bone-tendon healing of rotator cuff tear

BackgroundCaveolin-1 has been predicted, based on RNA transcriptome sequencing, as a key gene in rotator cuff tear (RCT) and it is related to fatty infiltration. This study aims to elucidate the upstream and downstream mechanism of Caveolin-1 in fatty infiltration and bone-tendon healing after RCT in rat models.MethodsDifferentially expressed genes related to RCT were screened, followed by functional enrichment analysis and protein-protein interaction analysis. GATA6 was overexpressed and Caveolin-1 was knocked down in tendon stem cells (TSCs) to evaluate their effects on the adipogenic differentiation of TSCs. In addition, a RCT rat model was constructed and injected with lentivirus carrying oe-GATA6, oe-Caveolin-1 alone or in combination to assess their roles in fatty infiltration and bone-tendon healing.Results and conclusionCaveolin-1 was identified as a key gene involved in the RCT process. In vitro results demonstrated that Caveolin-1 knockdown inhibited adipogenic differentiation of TSCs by activating the cAMP/PKA pathway. GATA6 inhibited the transcription of Caveolin-1 and inhibited its expression, thus suppressing the adipogenic differentiation of TSCs. In vivo data confirmed that GATA6 overexpression activated the cAMP/PKA pathway by downregulating Caveolin-1 and consequently repressed fatty infiltration, promoted bone-tendon healing, improved biomechanical properties and reduced the rupture risk of injured tendon in rats after RCT. Overall, this study provides novel insights into the mechanistic action of Caveolin-1 in the fatty infiltration and bone-tendon healing after RCT.

Strategies to promote tendon-bone healing after anterior cruciate ligament reconstruction: Present and future.

At present, anterior cruciate ligament (ACL) reconstruction still has a high failure rate. Tendon graft and bone tunnel surface angiogenesis and bony ingrowth are the main physiological processes of tendon-bone healing, and also the main reasons for the postoperative efficacy of ACL reconstruction. Poor tendon-bone healing has been also identified as one of the main causes of unsatisfactory treatment outcomes. The physiological process of tendon-bone healing is complicated because the tendon-bone junction requires the organic fusion of the tendon graft with the bone tissue. The failure of the operation is often caused by tendon dislocation or scar healing. Therefore, it is important to study the possible risk factors for tendon-bone healing and strategies to promote it. This review comprehensively analyzed the risk factors contributing to tendon-bone healing failure after ACL reconstruction. Additionally, we discuss the current strategies used to promote tendon-bone healing following ACL reconstruction.

TGF-β1 derived from macrophages contributes to load-induced tendon-bone healing in the murine rotator cuff repair model by promoting chondrogenesis

It has been established that mechanical stimulation benefits tendon-bone (T-B) healing, and macrophage phenotype can be regulated by mechanical cues; moreover, the interaction between macrophages and mesenchymal stem cells (MSCs) plays a fundamental role in tissue repair. This study aimed to investigate the role of macrophage-mediated MSC chondrogenesis in load-induced T-B healing in depth. C57BL/6 mice rotator cuff (RC) repair model was established to explore the effects of mechanical stimulation on macrophage polarization, transforming growth factor (TGF)-β1 generation, and MSC chondrogenesis within T-B enthesis by immunofluorescence and enzyme-linked immunosorbent assay (ELISA). Macrophage depletion was performed by clodronate liposomes, and T-B healing quality was evaluated by histology and biomechanics. In vitro, bone marrow-derived macrophages (BMDMs) were stretched with CELLOAD-300 load system and macrophage polarization was identified by flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). MSC chondrogenic differentiation was measured by histochemical analysis and qRT-PCR. ELISA and qRT-PCR were performed to screen the candidate molecules that mediated the pro-chondrogenic function of mechanical stimulated BMDMs. Mechanical stimulation promoted macrophage M2 polarization in vivo and in vitro. The conditioned media from mechanically stimulated BMDMs (MS-CM) enhanced MSC chondrogenic differentiation, and mechanically stimulated BMDMs generated more TGF-β1. Further, neutralizing TGF-β1 in MS-CM can attenuate its pro-chondrogenic effect. In vivo, mechanical stimulation promoted TGF-β1 generation, MSC chondrogenesis, and T-B healing, which were abolished following macrophage depletion. Macrophages subjected to appropriate mechanical stimulation could polarize toward the M2 phenotype and secrete TGF-β1 to promote MSC chondrogenesis, which subsequently augments T-B healing.

Human Trials on the Prevention of Tunnel Widening by the Emdogain in Anterior Cruciate Ligament Reconstruction.

Background Although anterior cruciate ligament reconstruction (ACLR) is an established procedure, some problems remain, such as bone tunnel widening after ACLR. In animal studies, Emdogain (EMD) prevented tunnel widening by promoting tendon-bone healing. This study aimed to evaluate the effects of EMD on the prevention of tunnel widening after anterior cruciate ligament (ACL) injury in humans. Methods Nineteen patients who underwent ACLR were included. Seven patients in the EMD group were administered EMDs into the femoral tunnel during ACLR, while 12 patients in the control group were not administered EMDs. After surgery, at two and four weeks and three, six, and 12 months, femoral and tibial tunnel widening were evaluated on computed tomography images. Anteroposterior laxity and clinical scores such as the Lysholm score, the International Knee Documentation Committee (IKDC) subjective form, and the Knee Injury and Osteoarthritis Outcome Score (KOOS) were assessed beforesurgery and 12 months postoperatively. Results Tunnel widening on the femoral side was significantly smaller in the EMD group than in the control group at two weeks. However, there was no significant difference between the two groups at 12 months. There were no significant differences in anteroposterior laxity and clinical scores between the groups before and 12 months after surgery. Conclusion EMD administration into the bone tunnel did not prevent tunnel widening at 12 months after ACLR, although tunnel widening of the femoral tunnel was reduced by EMD administration in the early phase.

Mesenchymal stem cells and macrophages and their interactions in tendon-bone healing

Mesenchymal stem cells and macrophages and their interactions in tendon-bone healing

The hydroxyapatite modified 3D printed poly L-lactic acid porous screw in reconstruction of anterior cruciate ligament of rabbit knee joint: a histological and biomechanical study

Background3D printing technology has become a research hotspot in the field of scientific research because of its personalized customization, maneuverability and the ability to achieve multiple material fabrications. The focus of this study is to use 3D printing technology to customize personalized poly L-lactic acid (PLLA) porous screws in orthopedic plants and to explore its effect on tendon-bone healing after anterior cruciate ligament (ACL) reconstruction.MethodsPreparation of PLLA porous screws with good orthogonal pore structure by 3D printer. The hydroxyapatite (HA) was adsorbed on porous screws by electrostatic layer-by-layer self-assembly (ELSA) technology, and PLLA-HA porous screws were prepared. The surface and spatial morphology of the modified screws were observed by scanning electron microscopy (SEM). The porosity of porous screw was measured by liquid displacement method. Thirty New Zealand male white rabbits were divided into two groups according to simple randomization. Autologous tendon was used for right ACL reconstruction, and porous screws were inserted into the femoral tunnel to fix the transplanted tendon. PLLA group was fixed with porous screws, PLLA-HA group was fixed with HA modified porous screws. At 6 weeks and 12 weeks after surgery, 5 animals in each group were sacrificed randomly for histological examination. The remaining 5 animals in each group underwent Micro-CT and biomechanical tests.ResultsThe pores of PLLA porous screws prepared by 3D printer were uniformly distributed and connected with each other, which meet the experimental requirements. HA was evenly distributed in the porous screw by ELSA technique. Histology showed that compared with PLLA group, mature bone trabeculae were integrated with grafted tendons in PLLA-HA group. Micro-CT showed that the bone formation index of PLLA-HA group was better than that of PLLA group. The new bone was uniformly distributed in the bone tunnel along the screw channel. Biomechanical experiments showed that the failure load and stiffness of PLLA-HA group were significantly higher than those of PLLA group.ConclusionsThe 3D printed PLLA porous screw modified by HA can not only fix the grafted tendons, but also increase the inductivity of bone, promote bone growth in the bone tunnel and promote bone integration at the tendon-bone interface. The PLLA-HA porous screw is likely to be used in clinic in the future.

A retrospective case series of the treatment of spontaneous quadriceps tendon rupture in patients with uremia and secondary hyperparathyroidism.

Spontaneous quadriceps tendon rupture (QTR) is a rare complication of uremia. Secondary hyperparathyroidism (SHPT) is considered the leading cause of QTR in uremia patients. QTR in patients with uremia and SHPT are treated with active surgical repair along with the treatment of SHPT using medication or parathyroidectomy (PTX). The impact of PTX for SHPT on tendon healing remains unclear. The purpose of this study was to introduce surgical procedures for QTR and to determine the functional recovery of the repaired quadriceps tendon (QT) after PTX. Between Jan 2014 and Dec 2018, eight uremia patients underwent PTX after a ruptured QT was repaired by figure-of-eight trans-osseous sutures with an overlapping tightening suture technique. Biochemical indices were measured before and one year after PTX to evaluate the control of SHPT. The changes in bone mineral density (BMD) were determined by comparing x-ray images at pre-PTX and during follow-up. The assessment of the functional recovery of the repaired QT was conducted at the last follow-up using multiple functional parameters. Eight patients (fourteen tendons) were retrospectively evaluated at an average follow-up of 3.46 ± 1.37 years after PTX. ALP and iPTH levels one year after PTX were significantly lower than at pre-PTX (P = 0.017, P < 0.001, respectively). Although there was no statistical differences compared to pre-PTX, serum phosphorus levels decreased and returned to normal one year after PTX (P = 0.101). BMD significantly increased at the last follow-up compared to pre-PTX. The average Lysholm score was 73.5 ± 11.07 and the average Tegner activity score was 2.63 ± 1.06. The active knee ROM after repair averaged an extension of 2.85 ± 3.78° to a flexion angle of 113.21 ± 10.12°. The quadriceps muscle strength was grade IV and the mean Insall-Salvati index was 0.93 ± 0.10 in all of the knees with tendon ruptures. All patients were able to walk without external help. Figure-of-eight trans-osseous sutures with an overlapping tightening suture technique is an economical and effective treatment for spontaneous QTR in patients with uremia and SHPT. PTX may promote tendon-bone healing in patients with uremia and SHPT.

Injectable FHE+BP composites hydrogel with enhanced regenerative capacity of tendon-bone interface for anterior cruciate ligament reconstruction.

Features of black phosphorous (BP) nano sheets such as enhancing mineralization and reducing cytotoxicity in bone regeneration field have been reported. Thermo-responsive FHE hydrogel (mainly composed of oxidized hyaluronic acid (OHA), poly-ε-L-lysine (ε-EPL) and F127) also showed a desired outcome in skin regeneration due to its stability and antibacterial benefits. This study investigated the application of BP-FHE hydrogel in anterior cruciate ligament reconstruction (ACLR) both in in vitro and in vivo, and addressed its effects on tendon and bone healing. This BP-FHE hydrogel is expected to bring the benefits of both components (thermo-sensitivity, induced osteogenesis and easy delivery) to optimize the clinical application of ACLR and enhance the recovery. Our in vitro results confirmed the potential role of BP-FHE via significantly increased rBMSC attachment, proliferation and osteogenic differentiation with ARS and PCR analysis. Moreover, In vivo results indicated that BP-FHE hydrogels can successfully optimize the recovery of ACLR through enhancing osteogenesis and improving the integration of tendon and bone interface. Further results of Biomechanical testing and Micro-CT analysis [bone tunnel area (mm2) and bone volume/total volume (%)] demonstrated that BP can indeed accelerate bone ingrowth. Additionally, histological staining (H&E, Masson and Safranin O/fast green) and immunohistochemical analysis (COL I, COL III and BMP-2) strongly supported the ability of BP to promote tendon-bone healing after ACLR in murine animal models.

BMP-2/TGF-β1 gene insertion into ligament-derived stem cells sheet promotes tendon-bone healing in a mouse.

Bone morphogenetic protein-2 (BMP-2) and transforming growth factor-β1 (TGF-β1) reportedly induce the osteogenic and tenogenic differentiation of anterior cruciate ligament (ACL)-derived stem cells (LDSCs), respectively. However, few studies have investigated the effect of BMP-2/TGF-β1 on the differentiation of LDSC. We developed a BMP-2/TGF-β1 gene insertion into an LDSC cell sheet that promotes tendon-bone healing in a mouse ACL reconstruction (ACLR) model. CD34+ LDSCs were isolated from human ACL stump tissues, virally transduced to express BMP-2 or TGF-β1, and then embedded within cell sheets. All mice underwent ACLR using an autograft wrapped with a cell sheet and were randomly divided into three groups: BMP-2-, TGF-β1-, and BMP-2/TGF-β1-transduced. At 4 and 8weeks, tendon-bone healing was evaluated by micro-CT, biomechanical test, and histological analysis. BMP-2 and TGF-β1 promoted the osteogenic and tenogenic differentiation of LDSC in vitro. BMP-2/TGF-β1-transduced LDSC sheet application contributed to early improvement in mean failure load and graft stiffness, accelerated maturation of the tendon-bone junction, and inhibited bone tunnel widening. Furthermore, reduced M1 macrophage infiltration and a higher M2 macrophage percentage were observed in the BMP-2/TGF-β1-transduced LDSC group. This work demonstrated that BMP-2 and TGF-β1 promoted CD34+ LDSCs osteogenic and tenogenic differentiation in vitro and in vivo, which accelerated the tendon-bone healing after ACLR using autografts wrapped with cell sheets in a mouse model.

GLI1 Deficiency Impairs the Tendon-Bone Healing after Anterior Cruciate Ligament Reconstruction: In Vivo Study Using Gli1-Transgenic Mice.

Hedgehog (Hh) signaling plays a fundamental role in the enthesis formation process and GLI-Kruppel family member GLI1 (Gli1) is a key downstream mediator. However, the role of Gli1 in tendon-bone healing after anterior cruciate ligament reconstruction (ACLR) is unknown. To evaluate the tendon-bone healing after ACLR in Gli1LacZ/LacZ (GLI1-NULL) mice, and compare Gli1LacZ/WT (GLI1-HET) and Gli1WT/WT wild type (WT) mice, a total of 45 mice, 15 mice each of GLI1-NULL, GLI1-HET and WT were used in this study. All mice underwent microsurgical ACLR at 12 weeks of age. Mice were euthanized at 4 weeks after surgery and were used for biomechanical testing, histological evaluation, and micro-CT analysis. The GLI1-NULL group had significantly lower biomechanical failure force, poorer histological healing, and lower BV/TV when compared with the WT and GLI1-HET groups. These significant differences were only observed at the femoral tunnel. Immunohistology staining showed positive expression of Indian hedgehog (IHH) and Patched 1(PTCH1) in all three groups, which indicated the activation of the Hh signal pathway. The GLI1 was negative in the GLI1-NULL group, validating the absence of GLI1 protein in these mice. These results proved that activation of the Hh signaling pathway occurs during ACL graft healing, and the function of Gli1 was necessary for tendon-bone healing. Healing in the femoral tunnel is more obviously impaired by Gli1 deficiency. Our findings provide further insight into the molecular mechanism of tendon-bone healing and suggest that Gli1 might represent a novel therapeutic target to improve tendon-bone healing after ACLR.

Strategies for promoting tendon-bone healing: Current status and prospects.

Tendon-bone insertion (TBI) injuries are common, primarily involving the rotator cuff (RC) and anterior cruciate ligament (ACL). At present, repair surgery and reconstructive surgery are the main treatments, and the main factor determining the curative effect of surgery is postoperative tendon-bone healing, which requires the stable combination of the transplanted tendon and the bone tunnel to ensure the stability of the joint. Fibrocartilage and bone formation are the main physiological processes in the bone marrow tract. Therefore, therapeutic measures conducive to these processes are likely to be applied clinically to promote tendon-bone healing. In recent years, biomaterials and compounds, stem cells, cell factors, platelet-rich plasma, exosomes, physical therapy, and other technologies have been widely used in the study of promoting tendon-bone healing. This review provides a comprehensive summary of strategies used to promote tendon-bone healing and analyses relevant preclinical and clinical studies. The potential application value of these strategies in promoting tendon-bone healing was also discussed.

Comparison of cortical versus cancellous bone fixation in tendon-to-bone healing with a rat trans-calcaneal suture model for Achilles tendon sleeve avulsion

BackgroundTrans-calcaneal suture technique is an economical and effective method for repairing Achilles tendon sleeve avulsion. Whether cancellous bone fixation upon this technique could accelerate tendon-to-bone healing is unknown. The purpose of this study is to compare the effect of cortical versus cancellous bone fixation on tendon–bone healing with a novel rat trans-calcaneal suture model.MethodsTrans-calcaneal suture treatment was carried out on the right hindlimb in male Sprague–Dawley rats (N = 80). They were randomly divided into the cortical group (Achilles fixed to the calcaneal cortical bone, n = 40) and the cancellous group (Achilles fixed to the calcaneal cancellous bone, n = 40). Gait analysis and immunohistochemistry were performed 1, 4, 7, and 14 days after the operation. Gross observation, biomechanical analysis, micro-CT, and histological analysis were performed 4 and 8 weeks after surgery. Independent-samples t tests were used for comparison between groups.ResultsAt 1, 4, and 7 days, the swing time of the affected limb in the cancellous group decreased, while the duty cycle, the maximum contact area, the print area, and the mean intensity increased significantly. The cross-sectional area of the tendon–bone junction in the cancellous group was smaller, and the failure load and stiffness were higher 4 weeks after the operation. The cancellous group showed more proportion of new bone and a relatively well-organized and dense connective tissue interface with better fibrocartilage-like tissue at 4 weeks after the operation. The ratio of ED2 + macrophages in the cancellous group was significantly higher than in the cortical group on 1, 4, 7, and 14 days. There were no significant differences in gait at 2 weeks, in appearance, biomechanics, new bone formation, and histology at 8 weeks after surgery between the two groups.ConclusionIn the new rat trans-calcaneal suture model, cancellous fixation can accelerate tendon-to-bone healing in the early stage, which perhaps is related to the abundant bone marrow tissue in the cancellous bone that modulates the inflammatory processes.

Investigation of the medium-term effect of osteoprotegerin/bone morphogenetic protein 2 combining with collagen sponges on tendon-bone healing in a rabbit.

Osteoprotegerin (OPG) and bone morphogenetic protein-2 (BMP-2) could be administered sequentially to promote tendon-bone healing. There remain several unresolved issues in our previously published study: a) the release kinetics of OPG/BMP-2 from the OPG/BMP-2/collagen sponge (CS) combination in vitro remained unclear; b) the medium-term effect of the OPG/BMP-2/CS combination was not analyzed. Hence, we design this study to address the issues mentioned above. 30 rabbits undergoing anterior cruciate ligament reconstruction (ACLR) with an Achilles tendon autograft randomly received one of the 3 delivery at the femoral and tibial tunnels: OPG/BMP-2, OPG/BMP-2/CS combination, and nothing (blank control). At 8 and 24 weeks post-surgery, the biomechanical tests and histologic analysis were used to evaluate the tendon-bone healing. In mechanical tests, the OPG/BMP-2/CS group showed a higher final failure load and stiffness than the other groups at 8 and 24 weeks. Additionally, the maximum stretching distance showed a decreasing trend. The mechanical failure pattern of samples shifted from a tunnel pull-away to a graft midsubstance rupture after OPG/BMP-2/CS-treated. From histological analysis, the OPG/BMP-2/CS treatment increased the amount of collagen fibers (collagen I and II) and promoted fibrocartilage attachment. CS as a carrier promotes the medium-term effect of OPG and BMP-2 on tendon-bone healing at the tendon-bone interface in a rabbit ACLR model. OPG, BMP-2 and CS were already applied in several clinical practice, but a further study of clinic use of OPG/BMP-2/CS is still needed.

Simvastatin promotes rat Achilles tendon-bone interface healing by promoting osteogenesis and chondrogenic differentiation of stem cells

To investigate the effect and mechanism of simvastatin on cell components of tendon-bone healing interface. The tendon-bone healing model was established by inserting the end of the Achilles tendon into the tibial tunnel on 24 rats, and simvastatin was used locally at the tendon-bone interface. Healing was evaluated at 8weeks by mechanical testing, micro-CT, and qualitative histology including H&E, Toluidine blue, and immunohistochemical staining. In vitro, bone marrow stromal cells (BMSCs) and tendon-derived mesenchymal stem cells (TDSCs) underwent osteogenic and chondrogenic differentiation respectively by plate co-culture. An analysis was performed on days 7 and 14 of cell differentiation. Biomechanical testing demonstrated a significant increase in maximum stiffness in the simvastatin-treated group. Micro-CT analysis showed that the bone tunnels in the simvastatin group were smaller in diameter and had higher bone density. H&E and Toluidine blue staining demonstrated that tendon-bone healing was significantly greater with better tissue arrangement and more extracellular matrix in the simvastatin-treated group than that in the control group, and immunohistochemical staining showed the expression of VEGF in simvastatin group was significantly higher. Histological staining and RT-PCR confirmed that simvastatin could promote the differentiation of co-cultured BMSCs and TDSCs into osteoblasts and chondroblasts, respectively. The effect of promoting osteogenic differentiation was more tremendous at 14days, while its effect on promoting chondroblast differentiation was more evident on the 7th day of differentiation. In conclusion, local administration of simvastatin can promote the tendon-bone healing by enhancing neovascularization, chondrogenesis, and osteogenesis in different stages of the tendon-bone healing process.

Combination of autologous osteochondral and periosteum transplantation effectively promotes fibrocartilage regeneration at the tendon-bone junction of the rotator cuff in rabbits.

Rotator cuff tendon-bone healing often leads to scarring and low biomechanical strength, resulting in a tendency to re-tear. This study examined whether combining autologous osteochondral transplantation and periosteum transplantation increases fibrocartilage transition zone regeneration and improves biomechanical fixation. A total of 48 New Zealand white rabbits were divided into the periosteum, autologous osteochondral, combination of autologous osteochondral and periosteum, and control groups. The supraspinatus tendon was cut from the greater tuberosity and repaired by different transplants. A total of 12 rabbits were used for histological examination (haematoxylin and eosin staining, Masson's staining and Safranin-O staining) at 4, 8 and 12weeks after the repair, and 36 rabbits were used for biomechanical tests (maximal failure load and stiffness). At 4weeks following the operation, each group had a large tendon-bone gap with a small number of disordered collagen fibres. At 8weeks, the tendon-bone gap was smaller than that before the operation, and the tendon-bone gap in each experimental group was smaller with neater and denser collagen fibres and chondrocytes than in the control group, with the osteochondral combined periosteum group having the best results. At 12weeks, the typical tendon-bone transitional structure was observed in the osteochondral combined periosteum group, and more collagen fibres and chondrocytes were generated in each group. The osteochondral combined periosteum group had the largest staining area and the largest amount of cartilage. The maximum tensile strength and stiffness of each group increased over time. There was no significant difference in each group's maximum tensile strength and stiffness at 4weeks after the operation. However, the maximum tensile strength and stiffness of the osteochondral combined periosteum group at 8 and 12weeks after operation were significantly higher than those of other groups (P < 0.05). Histological and biomechanical results show that autologous osteochondral transplantation combined with periosteum transplantation can effectively promote the regeneration of fibrous cartilage in the tendon-bone junction of the rotator cuff. It is concluded that this technique is a new treatment method to promote tendon-bone healing in the rotator cuff.

Anatomical and Interpositional Bursa Preservation Showed Similar Improved Tendon to Bone Healing Compared With the Bursa Removal in a Rat Rotator Cuff Tear Model

To compare the effects of anatomical preservation (AP) and interpositional preservation (IP) of subacromial bursa tissue on tendon-to-bone healing in a rat model of rotator cuff tear. In this study, 48 male Sprague-Dawley rats (average weight 283 g) underwent bilateral supraspinatus tendons severed by sharp incision and repaired immediately. The subacromial bursa tissues were completely removed in 16 rats, who served as the control (CON) group. The other 32 rats were randomly divided into 2 groups AP and IP between tendon and bone. Eight rats of each group were sacrificed for bilateral shoulders at 3 and 9 weeks after the operation, including 5 rats for biomechanical tests and 3 for histologic analysis. No significant differences in terms of biomechanical properties were observed among the groups 3 weeks after surgery. At 9 weeks, the maximum load and stiffness of the AP (32.95 ± 6.33 N, P= .029; 12.49 ± 3.17 N/mm, P < .001; respectively) and IP (33.58 ± 8.47 N, P= .015; 11.63 ± 2.84 N/mm, P= .010, respectively) groups were significantly superior to that of the CON group (26.59 ± 4.47 N; 8.42 ± 2.33 N/mm, respectively). More organized collagen and more mature tendon insertion were observed in AP and IP groups at the interface at 9 weeks, which means better tendon-to-bone healing compared with the CON group. The subacromial bursa plays a positive role in tendon-bone healing. Either anatomical preservation or interpositional preservation between tendon and bone can similarly facilitate the process of healing. Considering the additional surgical time and surgical manipulation, preserving the subacromial bursa at the anatomical position seems to be a better way to promote rotator cuff healing.

Tensionable Distal Biceps Tendon Repair With Intramedullary Knotless All-Suture Anchors and FiberLoop w/FiberTag Suture

Distal biceps tendon rupture is commonly repaired via bicortical drilling, extramedullary cortical button placement, and inlay tendon fixation. A retensionable technique with unicortical drilling, intramedullary knotless all-suture anchors placement, and onlay tendon fixation is presented, incorporating up-to-date advances in tendon-bone healing basic science, biceps tendon/radial tuberosity biomechanics, and knotless all-suture implant technology to facilitate radial tuberosity bone preservation, anatomic footprint restoration, improved suture-tendon connection security, and avoidance of drilling and implant-related injury to the posterior interosseous nerve.