Improve Tendon Healing Research Articles

Leveraging in vivo animal models of tendon loading to inform tissue engineering approaches.

Tendon injuries disrupt successful transmission of force between muscle and bone, resulting in reduced mobility, increased pain, and significantly reduced quality of life for affected patients. There are currently no targeted treatments to improve tendon healing beyond conservative methods such as rest and physical therapy. Tissue engineering approaches hold great promise for designing instructive biomaterials that could improve tendon healing or for generating replacement graft tissue. More recently, engineered microphysiological systems to model tendon injuries have been used to identify therapeutic targets. Despite these advances, current tissue engineering efforts that aim to regenerate, replace, or model injured tendons have largely failed due in large part to a lack of understanding of how the mechanical environment of the tendon influences tissue homeostasis and how altered mechanical loading can promote or prevent disease progression. This review article draws inspiration from what is known about tendon loading from in vivo animal models and identifies key metrics that can be used to benchmark success in tissue engineering applications. Finally, we highlight important challenges and opportunities for the field of tendon tissue engineering that should be taken into consideration in designing engineered platforms to understand or improve tendon healing.

Early intervention of extracorporeal shockwave therapy sustained positive long-term effect on rotator cuff healing: A randomized controlled trial with 3-year follow-up

BackgroundThe long-term effects of extracorporeal shockwave therapy (ESWT) on rotator cuff repair are unknown. ObjectivesTo investigate the functional outcomes and structural changes of ESWT at 3-year follow-up after rotator cuff repair. MethodsA randomized clinical trial was conducted, including patients who underwent rotator cuff repair. The patients were assigned to two groups based on whether they underwent radial ESWT 3 months postoperatively. The ESWT Group received 5 weeks of rehabilitation and ESWT weekly, whereas the CONTROL Group received only rehabilitation. Visual analog scale (VAS) pain score and functional scores were analyzed at 3 months (baseline), 6 months, and 3 years follow-up. In addition, MRI and ultrasonography were used to assess tendon maturation, integrity, tendon quality, acromiohumeral distance (AHD), and muscle fatty infiltration. ResultsFinally, 32 participants completed all the assessments. At the final follow-up, 2 patients in the ESWT Group (16.5 %) versus one patient in the CONTROL Group (6.25 %) had rotator cuff failure (P = 0.176). The ESWT treatment showed similar clinical outcomes in VAS-pain score, functional scores, tendon quality, AHD, and muscle fatty infiltration versus the CONTROL Group (Ps > 0.05). MRI analysis indicated improved tendon healing after ESWT treatment at both 6-month (P = 0.036) and 3-year follow-up (P = 0.028). ConclusionEarly intervention with radial ESWT sustained long-term effects on the healing of the repaired rotator cuff and similar functional outcomes at long-term follow-up compared with standard rehabilitation.

Effect of polydeoxyribonucleotide and polynucleotide on rotator cuff healing and fatty infiltration in a diabetic rat model

Failure rate after chronic rotator cuff repair is considerably high. Moreover, diabetes mellitus is known as a compromising factor of rotator cuff tear. The effect of Polydeoxyribonucleotide (PDRN) and polynucleotide (PN) on tendon healing and fatty infiltration is unclear as tissue regeneration activator in diabetic state. Therefore, a diabetic rat model with chronic rotator cuff tear was made for mechanical, histologic and blood tests. In the animal study using a diabetic rat cuff repair model, the administration of PDRN and PN increased the load to failure of repaired cuffs and improved tendon healing and decreased fatty infiltration. Also, the plasma levels of vascular endothelial growth factor and fibroblast growth factor were elevated in PDRN and PN administrated groups. We concluded that PDRN and PN appear to boost tendon recovery and reduce the presence of fatty infiltration following cuff repair in diabetic state. Also, PN showed a later onset and a longer duration than PDRN associated with the mean plasma growth factors.

Effect of a single versus serial platelet-rich plasma injection on the healing of acute patellar tendon defect: an experimental study

BackgroundThere is no consensus on the frequency and timing of platelet-rich plasma (PRP) injection in tendon healing. We aimed to evaluate the effectiveness of single versus multiple PRP injections in the healing of patellar tendon defects in the experimental model, through histological and biomechanical investigation.MethodsForty-four male skeletally mature Dutch rabbits were randomly divided into the five study groups ( A, B,C, D,E). After creating a longitudinal acute patellar tendon defect on both knees (One-third the width of the patella tendon), the right legs of the rabbits were used as the intervention group and the left legs as the control groups. Animals in groups A, B, and C were euthanized on days 7, 14, and 28, respectively, after the first PRP injection. Animals in group D received the second PRP injection on day 10 and was euthanized on day 14. Animals in group D received the second and third PRP injections on days 10 and 20, respectively, and were euthanized on day 28. The outcomes were evaluated histologically (modification of Movin’s Grading) and biomechanically.ResultsThe inflammatory condition was exaggerated in groups D and E. Load at failure was higher in the non-injected side of groups D and E, while there was no significant difference between the right and left legs of the three groups A, B and C. In other word, groups with a single PRP injection were more resistant to the increasing load compared to the groups with multiple PRP injections.ConclusionsPRP improves tendon healing if injected early after injury, while its injection after the initial phase of injury hampers tendon healing. In addition, a single PRP injection seems to be more effective than multiple PRP injection. Therefore, in cases where PRP injection is indicated for tendon repair, such as acute tendon injury, we recommend using a single PRP injection during tendon repair surgery.

A conserved transcription factor regulatory program promotes tendon fate.

Tendons, which transmit force from muscles to bones, are highly prone to injury. Understanding the mechanisms driving tendon fate would impact efforts to improve tendon healing, yet this knowledge is limited. To find direct regulators of tendon progenitor emergence, we performed a zebrafish high-throughput chemical screen. We established forskolin as a tenogenic inducer across vertebrates, functioning through Creb1a, which is required and sufficient for tendon fate. Putative enhancers containing cyclic AMP (cAMP) response elements (CREs) in humans, mice, and fish drove specific expression in zebrafish cranial and fin tendons. Analysis of these genomic regions identified motifs for early B cell factor (Ebf/EBF) transcription factors. Mutation of CRE or Ebf/EBF motifs significantly disrupted enhancer activity and specificity in tendons. Zebrafish ebf1a/ebf3a mutants displayed defects in tendon formation. Notably, Creb1a/CREB1 and Ebf1a/Ebf3a/EBF1 overexpression facilitated tenogenic induction in zebrafish and human pluripotent stem cells. Together, our work identifies the functional conservation of two transcription factors in promoting tendon fate.

Exploring Ascorbic Acid's Role in Orthopedic Practices: Present Theories, Innovative Approaches, and Prospects.

In the human body, ascorbic acid (AA) is known for its potent antioxidant and reducing properties and also plays a vital role in supporting the growth of bones and cartilage. It has been used extensively in orthopedicsurgery. Ongoing studies under the umbrella of ascorbic acidresearch investigate its impact on bone and tendon physiology, as well as its influence on joint replacement and postoperative pain. The majority of both laboratory and human studies link the usage of ascorbic acidto enhanced bone health and improved tendon healing. Recent literature suggest that ascorbic acidadministration may have a positive impact on the outcome of orthopedic procedures. On the other hand, controversy exists regarding the efficacy of ascorbic acidin reducing the incidence of complex regional pain syndrome. In brief, the effectiveness of ascorbic acidin enhancing orthopedic procedure outcomes remains a subject of ongoing investigation. Although certain studies have hinted at the potential positive influence of ascorbic acidon these outcomes, further research is required to validate its effectiveness and ascertain the ideal dosage and method of administration for maximizing its anticipated advantages. To establish the efficacy of ascorbic acidin improving orthopedic procedure outcomes, rigorous human trials of high quality are imperative. The aim of this review was to provide an overview of ascorbic acid's utilization in orthopedic practices and to pinpoint prospective areas for future research.

Current research trends on the effect of diabetes mellitus on rotator cuff tendon healing/tendinopathy.

Rotator cuff tendon tears are a leading cause of shoulder pain. They are challenging to treat, and tendon-bone healing has a high failure rate despite successful surgery. Tendons connect the muscles and bones, which make them important for the body's overall mobility and stability. Metabolic diseases, including diabetes or high blood pressure, can affect the healing process after repair of a damaged tendon. With a global incidence of 9.3%, diabetes is considered as a significant risk factor for rotator cuff tendon healing because it causes structural, inflammatory, and vascular changes in the tendon. However, the mechanisms of how diabetes affects tendon healing remain unknown. Several factors have been suggested, including glycation product accumulation, adipokine dysregulation, increased levels of reactive oxygen species, apoptosis, inflammatory cytokines, imbalanced matrix-metalloproteinase-to-tissue-inhibitor ratio, and impaired angiogenesis and differentiation of the tendon sheath. Despite the effects of diabetes on tendon function and healing, few treatments are available to improve recovery in these patients. This review summarizes the current literature on the pathophysiological changes of the tendon in diabetes and hyperlipidemia. Preclinical and clinical evidence regarding the association between diabetes and tendon healing is presented. Moreover, current approaches to improve tendon healing in patients with diabetes are reviewed.

Leukocyte-Poor Platelet-Rich Plasma as an Adjuvant to Arthroscopic Rotator Cuff Repair Reduces the Retear Rate But Does Not Improve Functional Outcomes: A Double-Blind Randomized Controlled Trial

Background: Whether the use of PRP as an adjuvant of rotator cuff repairs leads to improved tendon healing and better functional outcomes remains unclear in clinical evidence. Purpose: The main purpose of this study was to assess whether the use of leukocyte-poor platelet-rich plasma (LP-PRP) as an adjuvant to arthroscopic rotator cuff repair (ARCR) decreases the rate of retears compared with a control group. The secondary objective was to analyze whether LP-PRP improves patient-reported outcomes. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: This was a double-blind randomized controlled trial at a single center. A consecutive series of 96 patients with rotator cuff tears <3 cm were enrolled and randomly allocated to the control group (double-row suture-bridge ARCR alone [n = 48]) and the PRP group (double-row suture-bridge repair, followed by 1 LP-PRP injection during surgery [n = 48]). The visual analog scale (VAS) for pain, the American Shoulder and Elbow Surgeons (ASES) score, the Single Assessment Numeric Evaluation (SANE), and the Pittsburgh Sleep Quality Index (PSQI) were administered preoperatively and at 6- and 12-month follow-up. Magnetic resonance imaging (MRI) was performed to evaluate tendon integrity at 6-month follow-up. Both patients and assessors were blinded to the intervention received during surgery. Results: The mean patient age was 56.1 ± 2.98 years. Of the 96 patients, 90 had MRI performed at 6 months after surgery (94% radiological follow-up). The retear rate in the PRP group was 15.2% (7/46 [95% CI, 6%-28%]), which was lower than that in the control group of 34.1% (15/44 [95% CI, 20%-49%]) (P = .037). Therefore, the risk ratio of ruptures in patients exposed to LP-PRP was 0.44 (95% CI, 0.2-0.9; P = .037). Overall, the ASES, VAS, SANE, and PSQI scores showed a statistical improvement after surgery (P < .001). There were no significant differences in functional scores between the groups. Most of the patients exceeded the minimal clinically important difference for the ASES, SANE, and VAS without significant differences between the groups. Conclusion: In patients with rotator cuff tears <3 cm undergoing double-row suture-bridge repair, a 5-mL dose of LP-PRP injected at the tendon-bone interface significantly reduced the retear rate. However, the use of LP-PRP in terms of postoperative pain and patient-reported outcomes failed to show clinically meaningful effects. Registration: NCT04703998 (ClinicalTrials.gov identifier).

Early Postoperative Stiffness After Arthroscopic Rotator Cuff Repair Correlates With Improved Tendon Healing

PurposeThis study assessed if early postoperative stiffness predicts long-term stiffness and its relationship with repair integrity in arthroscopic rotator cuff repair (ARCR) patients. MethodsSingle-center retrospective study. 427 patients undergoing primary ARCR by a board-certified orthopaedic surgeon over four years were considered. Patients with at least one year of follow-up were categorized into stiff and non-stiff groups based on their range of motion (ROM) at three months postoperatively. Stiffness was defined as passive forward flexion <120°, external rotation <30°, or internal rotation below L3. We evaluated clinical outcomes using demographics, ROM, Constant Shoulder (CS) score, University of California, Los Angeles (UCLA) score, and visual analog scale (VAS) for pain preoperatively and at 3, 6, and 12 months postoperatively. Stiffness, retear rates, and tendon integrity were assessed via MRI at 12 months. ResultsOf 155 patients meeting the inclusion criteria, 68 (43.9%) were stiff, and 87 (56.1%) were non-stiff. The stiff group had significantly lower preoperative CS and UCLA scores (P=.013/.014) and higher VAS score (P=.034). At 3 months, this group showed lower ROM and functional scores (P<.001), persisting at 6 and 12 months (except internal rotation) (P<.001). Their 12-month VAS score was higher (P=.024). Postoperative stiffness occurred in 10.3% of the stiff group and 2.3% of the non-stiff group (P=.035). The 12-month retear rate was 5.9% in the stiff group and 17.2% in the non-stiff group (P=.032). Minimal clinically important difference (MCID) analysis indicated ROM changes but limited functional score changes in the two groups. ConclusionThis study showed that early postoperative shoulder stiffness correlates with lower preoperative functional scores and higher pain levels. Shoulder stiffness at three months post-ARCR predicts 12-month shoulder stiffness but indicates better tendon integrity. While early stiffness is linked to lower functional scores and more pain, its long-term clinical impact seems limited.

Clinical Outcomes and Tendon Healing After Arthroscopic Isolated Subscapularis Tendon Repair: Results at Midterm Follow-up.

Few studies have reported clinical outcomes and tendon healing rates after arthroscopic isolated subscapularis (SSC) repair (AISR). The primary purpose of this study was to evaluate clinical outcomes and tendon healing after AISR. It was hypothesized that AISR would result in satisfactory clinical outcomes along with a high rate of tendon healing at the midterm follow-up. The secondary purpose was to assess the influence of tear size and muscle atrophy on SSC tendon healing and patient-reported outcomes. It was hypothesized that both would be negatively correlated with healing but would have no effect on clinical outcomes . Case series; Level of evidence, 4. A retrospective analysis was conducted on prospectively collected data for 77 patients who underwent primary AISR between 2011 and 2021 at a single institution, with a minimum 2-year postoperative follow-up for all patients. Functional outcomes were assessed using the American Shoulder and Elbow Surgeons (ASES) score, the Subjective Shoulder Value (SSV), and the visual analog scale for pain. Repair techniques and concomitant procedures were also collected. SSC tendon healing was evaluated via ultrasound at the final follow-up. Linear regression analysis was performed to determine factors affecting SSC healing. The mean follow-up was 58.1 ± 3.3 months. ASES scores significantly improved from 41.5 to 81.6, and the SSV improved from 38.2 to 80.5 (P < .01 for both). Among the 40 patients (51.9%) who underwent postoperative ultrasound, 87.5% showed complete tendon healing. There were no significant differences in outcome scores between healed and unhealed tendons. Increased muscle atrophy and larger tears were correlated with failure of SSC healing (β = -0.285 [P = .015] and β = -0.157 [P = .045], respectively). Improved clinical outcomes and an overall high rate of tendon healing were seen at the midterm follow-up after AISR. Smaller tear sizes with less muscle atrophy were correlated with improved tendon healing. However, even when the tendon incompletely healed, the procedure improved functional outcomes.

TENDON BIOENGINEERING: CHALLENGES FOR CLINICAL APPLICATION

Tendons mainly consist of collagen in order to withstand high tensile forces. Compared to other, high turnover tissues, cellularity and vascularity in tendons are low. Thus, the natural healing process of tendons takes long and can be problematic. In case of injury to the enthesis, the special transition from tendon over cartilage to bone is replaced by a fibrous scar tissue, which remains an unsolved problem in rotator cuff repair.To improve tendon healing, many different approaches have been described using scaffolds, stem cells, cytokines, blood products, gene therapy and others. Despite promising in vitro and in vivo results, translation to patient care is challenging. In clinics however, tendon auto- or allografts remain still first choice to augment tendon healing if needed.Therefore, it is important to understand natural tendon properties and natural tendon healing first. Like in other tissues, senescence of tenocytes seems to play an important role for tendon degeneration which is interestingly not age depended. Our in vivo healing studies have shown improved and accelerated healing by adding collagen type I, which is now used in clinics, for example for augmentation of rotator cuff repair. Certain cytokines, cells and scaffolds may further improve tendon healing but are not yet used routinely, mainly due to missing clinical data, regulatory issues and costs.In conclusion, the correct diagnosis and correct first line treatment of tendon injuries are important to avoid the necessity to biologically augment tendon healing. However, strategies to improve and accelerate tendon healing are still desirable. New treatment opportunities may arise with further advances in tendon engineering in the future.

TENOCYTES THROUGH SPACE AND TIME: DETERMINING THE FATE OF TENDON HEALING

Tendon injuries present a major clinical challenge, as they necessitate surgical intervention and are prone to fibrotic progression. Despite advances in physical therapy and surgical technique, tendons fail to return to full native functioning, underlining the need for a biological therapeutic to improve tendon healing. Myofibroblasts are activated fibroblasts that participate in the proliferative and remodeling phases of wound healing, and while these matrix-producing cells are essential for proper healing, they are also linked to fibrotic initiation. A subset of tenocytes has been shown to give rise to the myofibroblast fate, and potentially contribute to fibrotic tendon healing. A viable anti-fibrotic therapy in other tissues has been reprogramming the fibroblast-myofibroblast differentiation route, avoiding a more pro-fibrotic myofibroblast phenotype. Thus, defining the molecular programs that underlie both physiological and pathological tendon healing is critical for the development of potential pharmacologic treatments. Towards that end, we have taken advantage of spatial transcriptomics, using the tenocyte marker Scleraxis as a tool, and have outlined three major spatiotemporally distinct tenocyte differentiation trajectories (synthetic, proliferative, and reactive) following acute tendon injury in mouse FDL. We have further outlined key transcriptional controls that may be manipulated to alter the differentiation process and influence the resulting myofibroblast phenotype, thereby promoting regenerative tendon healing.

3D BIOMIMETIC CONSTRUCTS STEER STEM CELL COMMITMENT BY SYNERGISTIC MODULATION OF BIOPHYSICAL CUES AND GROWTH FACTOR SIGNALLING

Tendon diseases are prevalent health concerns for which current therapies present limited success, in part due to the intrinsically low regenerative ability of tendons. Therefore, tissue engineering presents a potential to improve this outcome. Here, we hypothesize that a concurrent control over both biophysical and biochemical stimuli will boost the tenogenic commitment of stem cells, thus promoting regeneration. To achieve this, we combine molecularly imprinted nanoparticles (MINPs), which act as artificial amplifiers for endogenous growth factor (GF) activity, with bioinspired anisotropic hydrogels2 to manufacture 3D tenogenic constructs. MINPs were solid phase-imprinted using a TGF-β3 epitope as template and their affinity for the target was assessed by SPR and dot blot. Magnetically-responsive microfibers were produced by cryosectioning electrospun meshes containing iron oxide nanoparticles. The constructs were prepared by encapsulating adipose tissue-derived stem cells (ASCs), microfibers, and MINPs within gelatin hydrogels, while aligning the microfibers with an external magnetostatic field during gelation. This allows an effective modulation of hydrogel fibrillar topography, mimicking the native tissue's anisotropic architecture. Cell responses were analyzed by multiplex immunoassay, quantitative polymerase chain reaction, and immunocytochemistry. MINPs showed an affinity for the template comparable to monoclonal antibodies. Encapsulated ASCs acquired an elongated shape and predominant orientation along the alignment direction. Cellular studies revealed that combining MINPs with aligned microfibers increased TGF-β signaling via non-canonical Akt/ERK pathways and upregulated tendon-associated gene expression, contrasting with randomly oriented gels. Immunostaining of tendon-related proteins presented analogous outcomes, corroborating our hypothesis.Our results thus demonstrate that microstructural cues and biological signals synergistically direct stem cell fate commitment, suggesting that this strategy holds potential for improving tendon healing and might be adaptable for other biological tissues. The proposed concept highlights the GF-sequestering ability of MINPs which allows a cost-effective alternative to recombinant GF supplementation, potentially decreasing the translational costs of tissue engineering strategies.Acknowledgements: The authors acknowledge the funding from the European Union's Horizon 2020 under grant No. 772817; from FCT/MCTES for scholarships PD/BD/143039/2018 &amp; COVID/BD/153025/2022 (S.P.B.T.), and PD/BD/129403/2017 (S.M.B.), co-financed by POCH and NORTE 2020, under the Portugal 2020 partnership agreement through the European Social Fund, for contract 2020.03410.CEECIND (R.M.A.D.) and project 2022.05526.PTDC; and from Xunta de Galicia for grant ED481B2019/025 (A.P.).

FGF-2 enriched nanofiber scaffold for advancing achilles tendon healing: a comparative experimental investigation.

Achilles tendon rupture is a common and debilitating injury that significantly impacts mobility and quality of life. Effective treatment options that promote faster and more complete healing are needed. Fibroblast growth factor-2 (FGF-2) has shown potential in enhancing tendon repair. This study aims to investigate the efficacy of FGF-2 in promoting tendon healing in a rat model of Achilles tendon rupture, providing insights into its potential as a therapeutic option. Forty-eight rat hind legs with complete Achilles tendon ruptures were divided into four equal groups: the Sham (S) group (tendon repair only), the Polymer (P) group (tendon repair with scaffold wrapping), the Produced FGF-2 (PF) group (scaffold coated with lab-produced FGF-2), and the Commercial FGF-2 (CF) group (scaffold coated with commercially sourced FGF-2). Histological analyses at two and four weeks post-surgery evaluated healing based on nuclear morphology, vascularity, fibril organization, inflammation, and adipogenesis. At the end of the second week, no macroscopic healing was observed in one rat each from the S and P groups. By the end of the fourth week, macroscopic healing was observed in all groups. The S and P groups exhibited similarly severe fibril disorganization, pathological adipogenesis, and sustained inflammation, particularly at the fourth week. In contrast, the CF group demonstrated improved tendon healing with increased vascularity and extracellular matrix, lower inflammatory cell infiltration, and better fibril organization. Pathological adipogenesis was absent in the CF group, especially at the fourth week. The PF group showed comparable improvements at the second week but experienced a relapse by the 4th week, with increased inflammation and adipogenesis. FGF-2 coated scaffolds significantly enhanced tendon healing in a rat Achilles tendon rupture model by improving fibril organization, increasing vascularity, and reducing inflammation and pathological adipogenesis. These findings suggest that FGF-2 could be a promising therapeutic option for accelerating tendon repair. Future perspectives on tendon repair will focus on enhancing FGF-2 delivery using innovative scaffolds, paving the way for more effective therapies and improved patient outcomes.

Preclinical assessment of IL-1β primed human umbilical cord mesenchymal stem cells for tendon functional repair through TGF-β/IL-10 signaling

BackgroundInadequate repair capacity and disturbed immune compartments are the main pathological causes of tendinopathy. Transplantation of mesenchymal stem cells (MSCs) become an effective clinic option to alleviate tendinopathy. Interleukin-1β (IL-1β) could confer on MSCs enhanced immunoregulatory capability to remodel the repair microenvironment favoring tissue repair. Therefore, IL-1β activated UC-MSCs (1βUC-MSCs) may exert favorable efficacy in promoting tendon repair in a preclinical tendinopathy rat model. MethodsTendon-derived stem cells (TDSCs) were isolated and characterized. In vitro, the levels of immunoregulatory-related cytokines such as IL-1β, IL-6, IL-10, and TGF-β secreted by 1βUC-MSCs and unprimed UC-MSCs was measured. And tendon-specific markers expressed by TDSCs cultured with primed cultured medium (CM) or unprimed CM were detected. In vivo, Achilles tendinopathy was induced by 30 μL collagenase I injection in Sprague Dawley rats. One week later, the rats were randomly injected with UC-MSCs primed with IL-1β (106 cells per tendon), UC-MSCs, or PBS. After rats were sacrificed, histological evaluation, electron microscopy, biomechanical tests, gait performance were conducted to evaluate the structural and functional recovery of Achilles tendons. The inflammation and metabolic state of the extracellular matrix, and the potential mechanism were assessed by immunohistochemical staining and Western blot. ResultsUC-MSCs were activated by IL-1β to secrete higher levels of IL-10 and TGF-β while the secretion levels of IL-6 and IL-1β were not changed significantly, promoting a higher expression level of COL I and TNMD in TDSCs under proinflammatory environment. In vivo, the transplanted 1βUC-MSCs could survive up to 5 weeks after injection with tenogenic differentiation and improved tendon healing histologically semi-quantified by modified Bonar scores. This structural regeneration was further confirmed by observation of ultrastructural morphology, and led to good functional recovery including improved biomechanical properties and gait performance. During this process, the inflammatory response and metabolism of the extracellular matrix was improved through TGF-β/IL-10 pathway. ConclusionThis study demonstrated that the transplantation of UC-MSCs activated by IL-1β exhibited satisfactory ability for promoting tendon functional repair in a tendinopathy rat model. During this process, the balance of inflammatory response and extracellular matrix metabolism was remodeled, and the TGF-β/Smad2/3 and IL-10 signaling pathways were activated simultaneously. We cautiously conclude that the IL-1β primed UC-MSCs could be a promising strategy for enhancing the ability of MSCs to treat tendinopathy.

The superior healing capacity of MRL tendons is minimally influenced by the systemic environment of the MRL mouse

Murphy Roths Large mice (MRL) exhibit improved tendon healing and are often described as a “super-healer” strain. The underlying mechanisms that drive the superior healing response of MRL remain a controversial subject. We utilized a tendon transplantation model between MRL and “normal-healer” B6-mice to differentiate between the contribution of MRL’s innate tendon and systemic environment to its improved healing capacity. Patellar tendons with a midsubstance punch injury were transplanted back into the same animal (autograft) or into an animal of the other strain (allograft). Findings at 4 weeks showed that the innate MRL tendon environment drives its improved healing capacity as demonstrated by improved stiffness and maximum load in MRL-grafts-in-B6-host-allografts compared to B6-autografts, and higher modulus in MRL-autografts compared to B6-graft-in-MRL-host-allografts. Groups with an MRL component showed an increase in pro-inflammatory cytokines in the 3 days after injury, suggesting an early enhanced inflammatory profile in MRL that ultimately resolves. A preserved range of motion of the knee joint in all MRL animals suggests a systemic “shielding effect” of MRL in regard to joint adhesiveness. Our findings 4-weeks post injury are consistent with previous studies showing tissue-driven improved healing and suggest that the systemic environment contributes to the overall healing process.

Estrogen and testosterone supplementation improves tendon healing and functional recovery after rotator cuff repair.

Failure of healing after rotator cuff repair (RCR) is common. The purpose of the current study was to evaluate the effect of systemic estrogen or testosterone supplementation on tendon healing after RCR. Seventy-two adult male mice were utilized for all experiments. The supraspinatus tendon was transected and repaired with 6-0 Prolene suture on the left shoulder of 51 animals. Mice were segregated into three groups postoperative: (1) vehicle group (VG; n = 18), (2) estrogen group (EST; n = 17), and (3) testosterone group (TST; n = 16). An unrepaired control group (unrepaired, n = 21) did not have surgery. Utilizing these animals, histological analysis, activity testing, biomechanical testing and RNA sequencing (RNA-seq) was performed. At 8 weeks post-RCR, TST, and EST supplementation improved the overall histologic structure of the repaired enthesis site. No differences in ultimate failure loads or stiffness were detected between VG, EST, and TST groups after biomechanical testing. RCR caused a reduction in wheel activity compared to unrepaired controls and supplementation with TST restored wheel activity. RNA-seq analysis indicated that estrogen and testosterone regulated different pathways associated with enthesis healing, including a suppression of inflammatory signaling. Supplementation with sex hormones improved the structure of the repaired tendon enthesis and significantly regulated expression of diverse pathways regulating multiple biological processes. Testosterone administration following RCR restored wheel activity without having a detrimental impact on biomechanical strength. Future human studies of sex hormone supplementation after RCR are warranted as supplementation in an animal model may improve tendon enthesis healing.

Combined Biologic Augmentation Strategies with Collagen Patch Graft, Microfractures, and Platelet Concentrate Injections Improve Functional and Structural Outcomes of Arthroscopic Revision Rotator Cuff Repair.

Arthroscopic revision rotator cuff repair (ARRCR) is challenging. Biologic strategies seem to be promising. The aim was to evaluate the effectiveness of the combination of microfractures of the greater tuberosity, augmentation with collagen patch graft, and platelet concentrate injections in ARRCR. A retrospective comparative study was conducted on patients that underwent ARRCR with a minimum follow-up of two years. Patients in the augmentation group underwent ARRCR combined with microfractures, collagen patch graft, and postoperative subacromial injections of platelet concentrate. A standard rotator cuff repair was performed in the control group. Constant-Murley score (CMS). disease-specific, health-related quality of life using the Disabilities of the Arm, Shoulder, and Hand (DASH) score; assessment of tendon integrity with magnetic resonance at least six months after surgery. Significance was set at p < 0.05. Forty patients were included. Mean follow-up was 36.2 ± 8.7 months. The mean CMS was greater in the augmentation group (p = 0.022). No differences could be found for DASH score. Healing failure rate was higher in the control group (p = 0.002). Biologic augmentation of ARRCR using a combination of microfractures, collagen patch graft, and subacromial injections of platelet concentrate is an effective strategy in improving tendon healing rate. retrospective cohort study, level III.

Equine tendon mechanical behaviour: Prospects for repair and regeneration applications.

Tendons are dense connective tissues that play an important role in the biomechanical function of the musculoskeletal system. The mechanical forces have been implicated in every aspect of tendon biology. Tendon injuries are frequently occurring and their response to treatments is often unsatisfactory. A better understanding of tendon biomechanics and mechanobiology can help develop treatment options to improve clinical outcomes. Recently, tendon tissue engineering has gained more attention as an alternative treatment due to its potential to overcome the limitations of current treatments. This review first provides a summary of tendon mechanical properties, focusing on recent findings of tendon mechanobiological responses. In the next step, we highlight the biomechanical parameters of equine energy-storing and positional tendons. The final section is devoted to how mechanical loading contributes to tenogenic differentiation using bioreactor systems. This study may help develop novel strategies for tendon injury prevention or accelerate and improve tendon healing.

Nutritional Supplements in the Clinical Management of Tendinopathy: A Scoping Review.

Tendinopathy has a high prevalence and incidence in the general population and among athletes, with a lack of consensus among medical practitioners on optimal management strategies. The objective of this scoping review was to evaluate current research on the use of nutritional supplements for treating tendinopathies, including what supplements have been used and what outcomes, outcome measures, and intervention parameters have been reported. Databases searched included Embase, SPORTDiscus, the Cochrane Library, MEDLINE, CINAHL, and AMED. This scoping review considered primary studies investigating nutritional supplements for tendinopathies and was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews. A total of 1527 articles were identified with 16 included in the review. Studies investigated a range of nutritional supplements in the clinical management of various tendinopathies, including several commercially available proprietary blends of several ingredients. TendoActive (mucopolysaccharides, type I collagen, and vitamin C) was used in 2 studies, TENDISULFUR (methylsulfonylmethane, hydrolyzed collagen, L-arginine, L-lysine, vitamin C, bromelain, chondroitin, glucosamine, Boswellia, and myrrh) was used in 3 studies, and Tenosan (arginine-L-alpha ketoglutarate, hydrolyzed collagen type I, methylsulfonylmethane, vitamin C, bromelain, and vinitrox) was used in 2 studies. Collagen peptides were used in 2 studies, with omega-3 fatty acids, combined fatty acids and antioxidants, turmeric rhizome combined with Boswellia, β-hydroxy β-methylbutyric, vitamin C in isolation and combined with gelatin, and creatine investigated in one study each. Despite a paucity of studies to date, findings from this review suggest that several nutritional compounds may be beneficial in the clinical management of tendinopathies, by exerting anti-inflammatory effects and improving tendon healing. Nutritional supplements may have potential as an adjunctive method to standard treatment methods such as exercise, where their pain-relieving, anti-inflammatory, and structural tendon effects may augment the positive functional outcomes gained from progressive exercise rehabilitation.