Evaluation of animal models and methods for assessing shoulder function after rotator cuff tear: A systematic review.

BACKGROUND AND OBJECTIVE: Restoring the shoulder function is a crucial demand of patients with rotator cuff (RC) tears. Most preclinical studies only focused on biological and mechanical measurements. Functional assessment was less investigated in the preclinical studies. This study aims to review the literature of shoulder function in animal models for RC tears and evaluate the strengths and weaknesses of different shoulder functional assessments and animal models. METHOD: A literature search for studies used RC tear animal models to evaluate changes in shoulder function was performed. We searched databases of PubMed, Embase, Web of Science, and Scopus from inception to September 2019. Animal species, functional parameters, injury and repair types, and study durations were summarised. Cluster analyses were then used to separate animal models with different levels of injury and timings of repair. The reliability and clinical relevance of the included assessments and animal models were then discussed. RESULTS: Fourteen animal studies that related to shoulder function in animal models of RC tears were reviewed. Five methods (gait analysis, passive range of motion test, open field test, staircase test, and running endurance test) to assess shoulder function were identified. Single or massive RC tendon tears and immediate or delayed RC repair models were found. We reported and discussed factors to be considered when researchers would select assessments and animal models for different study purposes. CONCLUSION: Based on current evidences, gait analysis is the most appropriate method to assess changes in shoulder function of animal models of RC tears. More studies are required to further elucidate the reliability of passive range of motion measurement, open field test, staircase test, and running endurance test. Models that use massive tears and delayed repair better represent the clinical condition found in humans. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Using more clinically relevant animal models and assessments for shoulder function identified in this review may help to investigate the value of preclinical researches and promote translation of preclinical interventions into clinical practices.

The effect of thermosensitive hydrogel platelet-rich-plasma complex in the treatment of partial tear of anterior cruciate ligament in rat model.

BACKGROUND/OBJECTIVE: The treatment of anterior cruciate ligament (ACL) partial tear is controversial. The reconstructive surgery is invasive while the prevalence of subsequent insufficiency after conservative treatment has been reported to range from 11% to 62%. Therefore, a new method that promotes tissue regeneration is needed. The aim of this study was to observe the healing of ACL partial tear biomechanically and histologically after the administration of a thermosensitive hydrogel platelet-rich-plasma (PRP) complex. METHODS: The complex was prepared according to a previously published protocol. One hundred and fifty 12-week-old male Sprague-Dawley rats were included and they were allocated into 4 groups. Lesion control group (Group 1), treatment group (Group 2), gel-only group (Group 3) and intact group (Group 4). Biomechanical testing, histological analysis (H&E and immunohistochemical staining) and scoring was performed. RESULTS: On gross observation, the treatment group showed a continuous ACL with slightly thickened synovium or a partially healed ACL at 6-week follow up. In the biomechanical testing at 6 weeks after surgery, the failure load of the treatment group was significantly superior when compared with the lesion control group (52.7±10.8N vs. 41.6±7.8N, p<0.01), but the failure load was not restored to level of the intact group (52.7±10.8N vs. 61.5±9.1N, p=0.037). The maturity index of wound sites showed no significant inter-group differences at any timepoints. However, an increased expression of vascular endothelial growth factor (VEGF) and pro-collagen I was detected. CONCLUSION: The thermosensitive hydrogel-PRP was shown to be effective in enhancing the healing of ACL partial tear in the rat model, and potentially this complex can be used as a treatment for patients with ACL partial tear. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The thermosensitive hydrogel-PRP is potentially translated to clinical use to treat patients with ACL partial tear by injection under arthroscopy or ultrasound guiding.

Bioactive Tape With BMP-2 Binding Peptides Captures Endogenous Growth Factors and Accelerates Healing After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: The anterior cruciate ligament (ACL) has poor regenerative capacity, and an injury leads to loss of function, limiting quality of life and increasing the incidence of osteoarthritis. Surgical interventions can stabilize the joint and improve functional recovery. The delivery of growth factors (GFs) enhances the healing process; however, this is complex in its regulation, is high in costs, has side effects, and can only be accomplished with supraphysiological concentrations and thus is currently not clinically feasible. However, the immobilization of a patient's endogenous GFs in biomaterials can overcome these problems. PURPOSE: To develop a method to capture endogenous bone morphogenetic protein-2 (BMP-2) and ultimately show enhanced ACL healing in vivo using this novel methodology. STUDY DESIGN: Controlled laboratory study. METHODS: BMP-2 binding peptides were synthetized, purified, and immobilized on polycaprolactone (PCL) films. The affinity between the peptide and human BMP-2 (hBMP-2) was confirmed with immunofluorescence and enzyme-linked immunosorbent assay. The C2C12 Luc reporter cell line was used to confirm the bioactivity of immobilized BMP-2. For in vivo experiments, the same functionalization technology was applied to the commercially available Polytape, and the functionalized tape was sutured together with the graft used for ACL reconstruction in rats. Each animal underwent reconstruction with either native Polytape (n = 3) or Polytape with BMP-2 binding peptides (n = 3). At 2 and 6 weeks after surgery, the graft was assessed by histology and micro-computed tomography. RESULTS: The covalent immobilization of the peptide in PCL was successful, allowing the peptide to capture hBMP-2, which remained bioactive and led to the osteogenic differentiation of C2C12. In vivo experiments confirmed the potential of the Polytape functionalized with the BMP-2 binding peptide to capture endogenous BMP-2, leading to enhanced bone formation inside the femoral and tibial tunnels and ultimately improving the graft's quality. CONCLUSION: The incorporation of BMP-2 binding peptides into materials used for ACL reconstruction can capture endogenous hBMP-2, which enhances the healing process inside the bone tunnels. CLINICAL RELEVANCE: These results demonstrate the potential of using synthetic peptides to endow biomaterials with novel biological functions, namely to capture and immobilize endogenous GFs.

Bone morphogenetic protein 13 stimulates cell proliferation and production of collagen in human patellar tendon fibroblasts.

BACKGROUND: Recombinant human (rh) bone morphogenetic protein 13 (BMP13) has been shown to induce the formation of tendon and ligament tissues in animal experiments. The role of BMP13 in tissue regeneration in human tendons remains unexplored, however. MATERIAL AND METHODS: We collected healthy human patellar tendon samples for histological examination and tendon fibroblast culture. The cultured cells were incubated in the presence and absence of rhBMP13 and the effect of the protein on cell proliferation was measured using 5-bromo-2'-deoxyuridine uptake. RESULTS: BMP13 was detectable by immunohistochemical staining in healthy patellar tendon samples, and was located exclusively in active tenoblasts and perivascular mesenchymal cells but not in interstitial tenocytes. The expression of proliferating cell nuclear antigen (PCNA) and pro-collagen type I showed a similar distribution. In vitro studies showed that rhBMP13 can increase proliferation of tendon fibroblasts and increase the gene expression of pro-collagen type I in tendon fibroblast culture. INTERPRETATION: Our findings indicate that BMP13 may be involved in the matrix remodeling process in adult tendon, and that it may play a role in tissue regeneration in tendons.

Increased expression of matrix metalloproteinase 1 (MMP1) in 11 patients with patellar tendinosis.

We studied the expression of procollagen type I, matrix metalloproteinase 1 (MMP1) and tissue inhibitor of metalloproteinase 1 (TIMP-1) by immunohistochemistry in human patellar tendinosis tissues and healthy patellar tendons. In situ gelatin zymography was used to detect collagenolytic activities. The productions of MMP1, TIMP1 and gelatinolytic activities were compared in cell cultures from tendinosis samples and controls. Tendinosis tissues and cultures showed an increase in the expression level of MMP1 and a decrease in that of TIMP1, a condition favoring collagen degradation. Gelatinolytic activities in tendinosis tissues and cultures were elevated. Collagenolysis is a striking feature in patellar tendinosis.