Evaluation of a Novel Degradable Synthetic Biomaterial Patch for Augmentation of Tendon Healing in a Large Animal Model

2018 ◽  
Vol 32 (05) ◽  
pp. 434-440 ◽  
Author(s):  
Wayne Gersoff ◽  
Chantelle Bozynski ◽  
Cristi Cook ◽  
Ferris Pfeiffer ◽  
Keiichi Kuroki ◽  
...  
Keyword(s):  
Biomechanical Testing ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Standard Of Care ◽  
Tendon Injury ◽  
Large Animal Model ◽  
Large Animal ◽  
Range Of Movement ◽  
Limb Function ◽  
Group Outcomes

AbstractTendon injury is common in sports. The standard of care (SOC) for tendon repair is surgical treatment. However, restored tendons often lack complete strength and functionality, and surgical repair is often unsuccessful. This controlled laboratory study investigates the healing of an Artelon patch (AP)-augmented tendon versus tendon repair alone in a preclinical canine patellar tendon defect model. Full-thickness proximal and distal flap defects were created in the patella tendons of eight purpose-bred research mongrel dogs. Dogs were randomly allocated into either the AP-augmented repair group or the SOC group (N = 8; four knees per group). Outcomes measures included limb function and pain; range of motion (ROM) and ultrasound assessment at 2, 4, and 8 weeks; and measurements of elongation, biomechanical testing, and histology at 8 weeks. Data were compared for statistically significant differences to preoperative measures and between groups (p < 0.05). The AP group had higher limb function scores compared with the SOC group at 2, 4, and 8 weeks, with statistically significant differences observed at 2 weeks (AP: 7.1 ± 1.4, SOC: 5.5 ± 0.4, p < 0.05) and 8 weeks (AP: 9.5 ± 0.7, SOC: 7.0 ± 0.9, p < 0.05). The ROM was significantly higher for the AP group at 4 weeks (AP: 105 degrees ± 4, SOC: 89 degrees ± 5, p < 0.05). Pain scores were statistically significantly lower in the AP group at 4 (AP: 0.6 ± 0.5, SOC: 2.2 ± 0.5) and 8 weeks (p < 0.05 for both comparisons). All animals in the AP group displayed full bridging tissue at week 4, while most animals of the SOC group displayed full bridging by week 8. Minimal tendon elongation was observed in both groups. Significantly more force was required to elongate tendons in the AP group compared with the SOC group (p < 0.05). Animals with AP-augmented tendon repair show an earlier regain of function, earlier regain of range of movement, less postoperative pain, and improved tendon strength when compared with animals treated with tendon repair alone.

scholarly journals Molecular Mechanisms of Fetal Tendon Regeneration Versus Adult Fibrous Repair

2021 ◽  
Vol 22 (11) ◽  
pp. 5619
Author(s):  
Iris Ribitsch ◽  
Andrea Bileck ◽  
Alexander D. Aldoshin ◽  
Maciej M. Kańduła ◽  
Rupert L. Mayer ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Molecular Mechanisms ◽  
Unmet Need ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Inflammatory Factors ◽  
Large Animal ◽  
Post Injury ◽  
Tendon Regeneration ◽  
Large Animal Models

Tendinopathies are painful, disabling conditions that afflict 25% of the adult human population. Filling an unmet need for realistic large-animal models, we here present an ovine model of tendon injury for the comparative study of adult scarring repair and fetal regeneration. Complete regeneration of the fetal tendon within 28 days is demonstrated, while adult tendon defects remained macroscopically and histologically evident five months post-injury. In addition to a comprehensive histological assessment, proteome analyses of secretomes were performed. Confirming histological data, a specific and pronounced inflammation accompanied by activation of neutrophils in adult tendon defects was observed, corroborated by the significant up-regulation of pro-inflammatory factors, neutrophil attracting chemokines, the release of potentially tissue-damaging antimicrobial and extracellular matrix-degrading enzymes, and a response to oxidative stress. In contrast, secreted proteins of injured fetal tendons included proteins initiating the resolution of inflammation or promoting functional extracellular matrix production. These results demonstrate the power and relevance of our novel ovine fetal tendon regeneration model, which thus promises to accelerate research in the field. First insights from the model already support our molecular understanding of successful fetal tendon healing processes and may guide improved therapeutic strategies.

scholarly journals Visually guided tube thoracostomy insertion comparison to standard of care in a large animal model

Injury ◽  
2017 ◽  
Vol 48 (4) ◽  
pp. 849-853 ◽  
Author(s):  
Matthew C. Hernandez ◽  
David Vogelsang ◽  
Jeff R. Anderson ◽  
Cornelius A. Thiels ◽  
Gregory Beilman ◽  
...  
Keyword(s):  
Animal Model ◽  
Standard Of Care ◽  
Tube Thoracostomy ◽  
Large Animal Model ◽  
Large Animal ◽  
Visually Guided

Effect of rhPDGF-BB-Coated Sutures on Tendon Healing in a Rat Model: A Histological and Biomechanical Study

2011 ◽  
Author(s):  
S. Cummings ◽  
J. Dines ◽  
C. K. Hee ◽  
H. K. Kestler ◽  
C. M. Roden ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tissue Repair ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Biomechanical Study ◽  
Growth Factor Delivery ◽  
Delivery Method

Delivering growth factors to the site of injury using a coated suture delivery method has been investigated recently as a means to augment tissue repair [1]. This is a practical approach for growth factor delivery, as sutures are the method of choice for most orthopaedic surgeons for soft tissue repairs. One advantage of growth factor-coated sutures in tendon repair is the potential to accelerate healing in vivo, thereby improving the outcome of the repair. In particular, platelet-derived growth factor-BB (PDGF-BB) is a well characterized wound healing protein known to be chemotactic and mitogenic for cells of mesenchymal origin, including tenocytes, and has been shown to improve healing when applied to animal models of tendon injury [2,3]. The aim of this study was to compare the quality of the tendon repair at four weeks post treatment with sutures coated with varying concentrations of rhPDGF-BB, relative to buffer-coated suture repairs.

Pifithrin-α, an inhibitor of p53 transactivation, alters the inflammatory process and delays tendon healing following acute injury

2007 ◽  
Vol 292 (1) ◽  
pp. R321-R327 ◽  
Author(s):  
David Marsolais ◽  
Claude H. Côté ◽  
Jérôme Frenette
Keyword(s):  
Extracellular Matrix ◽  
Inflammatory Process ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Acute Injury ◽  
Inflammatory Phase ◽  
Load To Failure ◽  
Transcription Factor P53

Transcription factor p53, which was initially associated with cancer, has now emerged as an important regulator of inflammation and extracellular matrix homeostasis, two processes highly relevant to tendon repair. The goal of this study was to evaluate the effect of a p53 transactivation inhibitor, namely, pifithrin-α, on the pathophysiological sequence following collagenase-induced tendon injury. Administration of pifithrin-α during the inflammatory phase reduced the accumulation of neutrophils and macrophages by 30 and 40%, respectively, on day 3 postinjury. Pifithrin-α failed to reduce the percentage of apoptotic cells following collagenase injection but delayed functional recovery. In uninjured Achilles tendons, pifithrin-α increased metalloprotease activity 2.4-fold. Accordingly, pifithrin-α reduced the collagen content in intact tendons as well as in injured tendons 7 days posttrauma compared with placebo. The effect of pifithrin-α on load to failure and stiffness was also evaluated. The administration of pifithrin-α during the inflammatory phase did not significantly decrease the functional deficit 3 days posttrauma. More importantly, load to failure and stiffness were significantly decreased in the pifithrin-α group from day 7 to day 28 compared with placebo. Overall, our results suggest that administration of pifithrin-α alters the inflammatory process and delays tendon healing. The present findings also support the concept that p53 can regulate extracellular matrix homeostasis in vivo.

scholarly journals A porcine bimicrobial abscess model for testing interventional treatments

2020 ◽  
Author(s):  
Yak-Nam Wang ◽  
Andrew A. Brayman ◽  
Keith T. Chan ◽  
Keith Richmond ◽  
Wayne L. Monsky ◽  
...  
Keyword(s):  
Animal Model ◽  
New Technologies ◽  
Defense Mechanism ◽  
Trauma Surgery ◽  
Standard Of Care ◽  
The Body ◽  
Large Animal Model ◽  
Histological Evaluation ◽  
Large Animal ◽  
Current Standard

AbstractBackgroundAbscess formation is a host defense mechanism to contain the spread of infection. Abscesses can affect any part of the body and are common sequelae to complications of trauma, surgery, systemic infections and other disease states. Most models for abscesses are in small animals. Pursuant to the goal of developing more advanced treatments for abscesses, we sought to develop a large animal model which would reasonably mimic a fluid-filled human abscess.MethodsDomestic swine were inoculated with a bimicrobial mixture of Bacteroides fragilis (B. fragilis) and Escherichia coli (E. coli) supplemented with an irritant (dextran). Inoculations were performed under ultrasound guidance in the muscle, subcutaneously or intradermally within the same animal. Fourteen days after inoculation, lesions were imaged with ultrasound, resected and prepared for histological evaluation.ResultsInjection of bimicrobial (aerobic and anaerobic) bacterial mixtures at multiple sites in a pig produced multiple lesions with histological features similar to encapsulated and multiloculated/multichamber abscesses often observed clinically in humans. Important salient features include the formation of a connective tissue capsule surrounding histologically nearly amorphous pus.ConclusionsThis paper provides the first description of a pig model for multiloculated abscesses. This animal model could potentially enable the evaluation of new technologies to replace or augment the current standard of care (image-guided percutaneous abscess drainage with antibiotics).

scholarly journals Transplant of Autologous Mesenchymal Stem Cells Halts Fatty Atrophy of Detached Rotator Cuff Muscle After Tendon Repair: Molecular, Microscopic, and Macroscopic Results From an Ovine Model

2021 ◽  
pp. 036354652110525
Author(s):  
Martin Flück ◽  
Stephanie Kasper ◽  
Mario C. Benn ◽  
Flurina Clement Frey ◽  
Brigitte von Rechenberg ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Muscle Fiber ◽  
Tendon Repair ◽  
Fat Free Mass ◽  
Large Animal Model ◽  
Ground Substance ◽  
Large Animal ◽  
Rotator Cuff Muscle ◽  
Fatty Atrophy ◽  
Fat Fraction

Background: The injection of mesenchymal stem cells (MSCs) mitigates fat accumulation in released rotator cuff muscle after tendon repair in rodents. Purpose: To investigate whether the injection of autologous MSCs halts muscle-to-fat conversion after tendon repair in a large animal model for rotator cuff tendon release via regional effects on extracellular fat tissue and muscle fiber regeneration. Study Design: Controlled laboratory study. Methods: Infraspinatus (ISP) muscles of the right shoulder of Swiss Alpine sheep (n = 14) were released by osteotomy and reattached 16 weeks later without (group T; n = 6) or with (group T-MSC; n = 8) electropulse-assisted injection of 0.9 Mio fluorescently labeled MSCs as microtissues with media in demarcated regions; animals were allowed 6 weeks of recovery. ISP volume and composition were documented with computed tomography and magnetic resonance imaging. Area percentages of muscle fiber types, fat, extracellular ground substance, and fluorescence-positive tissue; mean cross-sectional area (MCSA) of muscle fibers; and expression of myogenic (myogenin), regeneration (tenascin-C), and adipogenic markers (peroxisome proliferator-activated receptor gamma [PPARG2]) were quantified in injected and noninjected regions after recovery. Results: At 16 weeks after tendon release, the ISP volume was reduced and the fat fraction of ISP muscle was increased in group T (137 vs 185 mL; 49% vs 7%) and group T-MSC (130 vs 166 mL; 53% vs 10%). In group T-MSC versus group T, changes during recovery after tendon reattachment were abrogated for fat-free mass (–5% vs –29%, respectively; P = .018) and fat fraction (+1% vs +24%, respectively; P = .009%). The area percentage of fat was lower (9% vs 20%; P = .018) and the percentage of the extracellular ground substance was higher (26% vs 20%; P = .007) in the noninjected ISP region for group T-MSC versus group T, respectively. Regionally, MCS injection increased tenascin-C levels (+59%) and the water fraction, maintaining the reduced PPARG2 levels but not the 29% increased fiber MCSA, with media injection. Conclusion: In a sheep model, injection of autologous MSCs in degenerated rotator cuff muscle halted muscle-to-fat conversion during recovery from tendon repair by preserving fat-free mass in association with extracellular reactions and stopping adjuvant-induced muscle fiber hypertrophy. Clinical Relevance: A relatively small dose of MSCs is therapeutically effective to halt fatty atrophy in a large animal model.

scholarly journals Nonwoven-based gelatin/polycaprolactone membrane loaded with ERK inhibitor U0126 for treatment of tendon defects

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Yonghui Hou ◽  
Bingyu Zhou ◽  
Ming Ni ◽  
Min Wang ◽  
Lingli Ding ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Biomechanical Testing ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Rna Seq ◽  
Injury Model ◽  
New Treatment ◽  
Underlying Mechanisms ◽  
And Control

Abstract Background Tendon is a major component of musculoskeletal system connecting the muscles to the bone. Tendon injuries are very common orthopedics problems leading to impeded motion. Up to now, there still lacks effective treatments for tendon diseases. Methods Tendon stem/progenitor cells (TSPCs) were isolated from the patellar tendons of SD rats. The expression levels of genes were evaluated by quantitative RT-PCR. Immunohistochemistry staining was performed to confirm the presence of tendon markers in tendon tissues. Bioinformatics analysis of data acquired by RNA-seq was used to find out the differentially expressed genes. Rat patellar tendon injury model was used to evaluate the effect of U0126 on tendon injury healing. Biomechanical testing was applied to evaluate the mechanical properties of newly formed tendon tissues. Results In this study, we have shown that ERK inhibitor U0126 rather PD98059 could effectively increase the expression of tendon-related genes and promote the tenogenesis of TSPCs in vitro. To explore the underlying mechanisms, RNA sequencing was performed to identify the molecular difference between U0126-treated and control TSPCs. The result showed that GDF6 was significantly increased by U0126, which is an important factor of the TGFβ superfamily regulating tendon development and tenogenesis. In addition, NBM (nonwoven-based gelatin/polycaprolactone membrane) which mimics the native microenvironment of the tendon tissue was used as an acellular scaffold to carry U0126. The results demonstrated that when NBM was used in combination with U0126, tendon healing was significantly promoted with better histological staining outcomes and mechanical properties. Conclusion Taken together, we have found U0126 promoted tenogenesis in TSPCs through activating GDF6, and NBM loaded with U0126 significantly promoted tendon defect healing, which provides a new treatment for tendon injury.

scholarly journals CD146 Delineates an Interfascicular Cell Sub-Population in Tendon That Is Recruited during Injury through Its Ligand Laminin-α4

2021 ◽  
Vol 22 (18) ◽  
pp. 9729
Author(s):  
Neil Marr ◽  
Richard Meeson ◽  
Elizabeth F. Kelly ◽  
Yongxiang Fang ◽  
Mandy J. Peffers ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Focal Lesion ◽  
Post Injury ◽  
Surface Receptors ◽  
Basement Membrane Protein ◽  
Injury Model ◽  
Cell Niche

The interfascicular matrix (IFM) binds tendon fascicles and contains a population of morphologically distinct cells. However, the role of IFM-localised cell populations in tendon repair remains to be determined. The basement membrane protein laminin-α4 also localises to the IFM. Laminin-α4 is a ligand for several cell surface receptors, including CD146, a marker of pericyte and progenitor cells. We used a needle injury model in the rat Achilles tendon to test the hypothesis that the IFM is a niche for CD146+ cells that are mobilised in response to tendon damage. We also aimed to establish how expression patterns of circulating non-coding RNAs alter with tendon injury and identify potential RNA-based markers of tendon disease. The results demonstrate the formation of a focal lesion at the injury site, which increased in size and cellularity for up to 21 days post injury. In healthy tendon, CD146+ cells localised to the IFM, compared with injury, where CD146+ cells migrated towards the lesion at days 4 and 7, and populated the lesion 21 days post injury. This was accompanied by increased laminin-α4, suggesting that laminin-α4 facilitates CD146+ cell recruitment at injury sites. We also identified a panel of circulating microRNAs that are dysregulated with tendon injury. We propose that the IFM cell niche mediates the intrinsic response to injury, whereby an injury stimulus induces CD146+ cell migration. Further work is required to fully characterise CD146+ subpopulations within the IFM and establish their precise roles during tendon healing.

scholarly journals Basic Research on Tendon Repair: Strategies, Evaluation, and Development

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhi Jie Li ◽  
Qian Qian Yang ◽  
You Lang Zhou
Keyword(s):  
Wound Healing ◽  
Platelet Rich Plasma ◽  
Healing Process ◽  
Tendon Repair ◽  
Continuous Optimization ◽  
Tendon Healing ◽  
Basic Research ◽  
Clinical Problem ◽  
Tendon Injury ◽  
Wound Healing Process

Tendon is a fibro-elastic structure that links muscle and bone. Tendon injury can be divided into two types, chronic and acute. Each type of injury or degeneration can cause substantial pain and the loss of tendon function. The natural healing process of tendon injury is complex. According to the anatomical position of tendon tissue, the clinical results are different. The wound healing process includes three overlapping stages: wound healing, proliferation and tissue remodeling. Besides, the healing tendon also faces a high re-tear rate. Faced with the above difficulties, management of tendon injuries remains a clinical problem and needs to be solved urgently. In recent years, there are many new directions and advances in tendon healing. This review introduces tendon injury and sums up the development of tendon healing in recent years, including gene therapy, stem cell therapy, Platelet-rich plasma (PRP) therapy, growth factor and drug therapy and tissue engineering. Although most of these therapies have not yet developed to mature clinical application stage, with the repeated verification by researchers and continuous optimization of curative effect, that day will not be too far away.

SYNERGISTIC WRIST DYNAMIC SPLINT FOR FLEXOR TENDON REPAIR

2001 ◽  
Vol 13 (05) ◽  
pp. 231-241
Author(s):  
PEI-HSI CHOU ◽  
YOU-LI CHOU ◽  
KAI-NAN AN ◽  
GAU-TYAN LIN ◽  
FONG-CHIN SU ◽  
...  
Keyword(s):  
Flexor Tendon ◽  
Tendon Repair ◽  
Hand Surgery ◽  
Standard Of Care ◽  
Tendon Injury ◽  
Wrist Motion ◽  
Passive Motion ◽  
Dynamic Splint ◽  
Controlled Motion

Tendons are frequently injured by direct trauma. Tendon adhesions were a common sequel of tendon repair and are one of the most challenging problems in hand surgery. The concept of “controlled motion” gradually replaced “total immobilization” in the treatment of flexor tendon injuries and today represents a standard of care for all primary repaired flexor tendon injury. Use of controlled motion splints during the early stages of stages of tendon recovery in crease tendon gliding. However, how best to achieve passive motion and the effect of passive motion on tendon gliding have remained controversial subjects. Based on a series of recent experiments, the concept of “dynamic synergistic wrist motion splint” was established and evaluated. It was found that this synergistic wrist motion increases the tendon excursion due to eliminating the laxity and buckling of tendon in the regions between pulleys without introduce excessive amount of tension. The purpose of this study is to design and fabricate a dynamic splint based on this concept and define the nature coordinated motion between the wrist and finger joints due to the passive tension of the muscles in vivo. Parametric analysis will be conducted to achieve an optimum design with the consideration of anatomic constraints. Clinical trial of using such dynamic splint will be evaluated in the future.

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