Effects of patellar position and defect healing on in vitro stifle joint kinematics following removal of the central one-third of the patellar tendon in an ovine model

2010 ◽  
Vol 29 (4) ◽  
pp. 572-581 ◽  
Author(s):  
Nicky Bertollo ◽  
David James Bell ◽  
Yan Yu ◽  
William Robert Walsh
Keyword(s):  
Patellar Tendon ◽  
Joint Kinematics ◽  
Ovine Model ◽  
Defect Healing ◽  
Stifle Joint ◽  
Patellar Position

scholarly journals Combination of a Collagen Scaffold and an Adhesive Hyaluronan-Based Hydrogel for Cartilage Regeneration: A Proof of Concept in an Ovine Model

Cartilage ◽  
2021 ◽  
pp. 194760352198941
Author(s):  
Clara Levinson ◽  
Emma Cavalli ◽  
Brigitte von Rechenberg ◽  
Marcy Zenobi-Wong ◽  
Salim E. Darwiche
Keyword(s):  
Collagen Scaffold ◽  
Cartilage Regeneration ◽  
Repair Process ◽  
Single Step ◽  
Surrounding Tissue ◽  
Proof Of Concept ◽  
Ovine Model ◽  
Stifle Joint ◽  
Adjacent Cartilage

Objective Hyaluronic acid–transglutaminase (HA-TG) is an enzymatically crosslinkable adhesive hydrogel with chondrogenic properties demonstrated in vitro and in an ectopic mouse model. In this study, we investigated the feasibility of using HA-TG in a collagen scaffold to treat chondral lesions in an ovine model, to evaluate cartilage regeneration in a mechanically and biologically challenging joint environment, and the influence of the surgical procedure on the repair process. Design Chondral defects of 6-mm diameter were created in the stifle joint of skeletally mature sheep. In a 3-month study, 6 defects were treated with HA-TG in a collagen scaffold to test the stability and biocompatibility of the defect filling. In a 6-month study, 6 sheep had 12 defects treated with HA-TG and collagen and 2 sheep had 4 untreated defects. Histologically observed quality of repair tissue and adjacent cartilage was semiquantitatively assessed. Results HA-TG adhered to the native tissue and did not cause any detectable negative reaction in the surrounding tissue. HA-TG in a collagen scaffold supported infiltration and chondrogenic differentiation of mesenchymal cells, which migrated from the subchondral bone through the calcified cartilage layer. Additionally, HA-TG and collagen treatment led to better adjacent cartilage preservation compared with empty defects ( P < 0.05). Conclusions This study demonstrates that the adhesive HA-TG hydrogel in a collagen scaffold shows good biocompatibility, supports in situ cartilage regeneration and preserves the surrounding cartilage. This proof-of-concept study shows the potential of this approach, which should be further considered in the treatment of cartilage lesions using a single-step procedure.

Medial Patellofemoral Ligament Influence on Patellofemoral Joint Kinematics: An In-Vitro Analysis

2013 ◽  
Vol 29 (10) ◽  
pp. e116-e117 ◽  
Author(s):  
Stefano Zaffagnini ◽  
Francesca Colle ◽  
Bharat Sharma ◽  
Simone Bignozzi ◽  
Nicola Francesco Lopomo ◽  
...  
Keyword(s):  
Patellofemoral Joint ◽  
Medial Patellofemoral Ligament ◽  
Joint Kinematics ◽  
Vitro Analysis ◽  
In Vitro Analysis

Effects of Cyclic Stress on the Mechanical Properties of Cultured Collagen Fascicles from the Rabbit Patellar Tendon

2003 ◽  
Vol 125 (6) ◽  
pp. 893-901 ◽  
Author(s):  
Ei Yamamoto ◽  
Susumu Tokura ◽  
Kozaburo Hayashi
Keyword(s):  
Mechanical Properties ◽  
Tensile Strength ◽  
Patellar Tendon ◽  
Control Level ◽  
Quadratic Function ◽  
Peak Stress ◽  
Cyclic Stress ◽  
Original Strength

Effects of cyclic stress on the mechanical properties of collagen fascicles were studied by in vitro tissue culture experiments. Collagen fascicles (approximately 300 μm in diameter) obtained from the rabbit patellar tendon were applied cyclic load at 4 Hz for one hour per day during culture period for one or two weeks, and then their mechanical properties were determined using a micro-tensile tester. There was a statistically significant correlation between tensile strength and applied peak stress in the range of 0 to 5 MPa, and the relation was expressed by a quadratic function. The maximum strength (19.4 MPa) was obtained at the applied peak stress of 1.8 MPa. The tensile strength of fascicles were within a range of control values, if they were cultured under peak stresses between 1.1 and 2.6 MPa. Similar results were also observed in the tangent modulus, which was maintained at control level under applied peak stresses between 0.9 and 2.8 MPa. The stress of 0.9 to 1.1 MPa is equivalent to approximately 40% of the in vivo peak stress which is developed in the intact rabbit patellar tendon by running, whereas that of 2.6 to 2.8 MPa corresponds to approximately 120% of the in vivo peak stress. Therefore, the fascicles cultured under applied peak stresses of lower than 40% and higher than 120% of the in vivo peak stress do not keep the original strength and modulus. These results indicate that the mechanical properties of cultured collagen fascicles strongly depend upon the magnitude of the stress applied during culture, which are similar to our previous results observed in stress-shielded and overstressed patellar tendons in vivo.

scholarly journals Osteoclast-Derived Extracellular miR-106a-5p Promotes Osteogenic Differentiation and Facilitates Bone Defect Healing

2021 ◽  
Author(s):  
Yutong Wu ◽  
Hongbo Ai ◽  
Yuchi Zou ◽  
Jianzhong Xu
Keyword(s):  
Demineralized Bone Matrix ◽  
Bone Matrix ◽  
Signal Molecules ◽  
Calvarial Defect ◽  
Communication Mode ◽  
Defect Healing ◽  
Bone Defect Healing ◽  
Intercellular Communications

Abstract Small extracellular vesicles (sEVs) are considered to play critical roles in intercellular communications during normal and pathological processes since they are enriched with miRNAs and other signal molecules. In bone remodeling, osteoclasts generate large amounts of sEVs. However, there is very little research about whether and how osteoclast-derived sEVs (OC-sEVs) affect surrounding cells. In our study, microarray analysis identified miR-106a-5p highly enriched in OC-sEV. Further experiments confirmed that OC-sEVs inhibited Fam134a through miR-106a-5p and significantly promoted bone mesenchymal stem cell (BMSC) osteogenic mineralization in vitro. Next, we prepared sEV-modified demineralized bone matrix (DBM) as a repair scaffold, and used a calvarial defect mouse model to evaluate the pro-osteogenic activities of the scaffold. In vivo result indicated DBM modified with miR-106a-5p-sEVs showed an enhanced capacity of bone regeneration. This important finding further emphasizes that sEV-mediated miR-106a-5p transfer play critical roles in osteogenesis and indicate a novel communication mode between osteoclasts and BMSCs.

scholarly journals Intramuscular Injection of Botox Induces Tendon Atrophy and Senescence of Tendon-Derived Stem Cells

2020 ◽  
Author(s):  
Peilin Chen ◽  
Ziming Chen ◽  
Christopher Mitchell ◽  
Junjie Gao ◽  
Lianzhi Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mechanical Loading ◽  
Patellar Tendon ◽  
Intramuscular Injection ◽  
Vastus Lateralis ◽  
Collagen Fibre ◽  
Differentiation Capacity ◽  
Botox Injection

Abstract Background: Botulinum toxin (Botox) injection is in widespread clinical use for the treatment of muscle spasms and tendinopathy but the mechanism of action is poorly understood. Hypothesis: We hypothesised that the reduction of patellar-tendon mechanical-loading following intra-muscular injection of Botox results in tendon atrophy that is at least in part mediated by the induction of senescence of tendon-derived stem cells (TDSCs). Study Design: Controlled laboratory study Methods: A total of 36 mice were randomly divided in 2 groups (18 Botox-injected and 18 vehicle-only control). Mice were injected into to right vastus lateralis of quadriceps muscles either with Botox to induce mechanical stress deprivation of the patellar tendon or with normal saline as control. At 2 weeks post-injection, animals were euthanized prior to tissues harvest for either evaluation of tendon morphology or in vitro studies. TDSCs were isolated by cell-sorting prior to determination of viability, differentiation capacity and senescence markers, as well as assessing their response to mechanical loading in a bioreactor. Finally, to examine the mechanism of tendon atrophy in vitro, key proteins in the PTEN/AKT pathway were evaluated in TDSCs in both groups. Results: Two weeks after Botox injection, patellar tendons displayed atrophic features including tissue volume reduction and collagen fibre misalignment and increased degradation. The colony formation assay revealed the significantly reduced colony units of TDSCs in Botox injected group compared to controls. Multipotent differentiation capacity of TDSCs has also diminished after Botox injection. To examine if mechanical deprived TDSC is capable of forming tendon tissue, we used an isolated bioreactor system to culture 3D TDSCs constructs. The result showed that TDSCs from the Botox-treated group failed to restore tenogenic differentiation after appropriate mechanical loading. Examination of PTEN/AKT signalling pathway revealed that injection of Botox into quadriceps muscle causes PTEN/AKT mediated cell senescence of TDSCs. Conclusion: Intramuscular injection of Botox interferes with tendon homeostasis by inducing tendon atrophy and senescence of TDSCs. Botox injection may have long-term adverse consequences for the treatment of tendinopathy. Clinical relevance: Intramuscular Botox injection for tendinopathy and tendon injury could cause adverse effects in human tendons and re-evaluation of its long-term efficacy is warranted.

Hypoxia promotes tenocyte differentiation of mesenchymal stem cells

2020 ◽  
Author(s):  
Guanyin Chen ◽  
wangqian zhang ◽  
Jintao Gu ◽  
Yuan Gao ◽  
Lei He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Patellar Tendon ◽  
Tendon Repair ◽  
Clinical Results ◽  
Tendon Injury ◽  
Tenogenic Differentiation ◽  
Tgf Β1

Abstract Background: Tendon injury is a common but tough medical problem. Unsatisfactory clinical results have been reported in tendon repair using mesenchymal stem cells (MSCs) therapy, creating a need for a better strategy to induce MSCs to tenogenic differentiation. This study was designed to investigate the role of hypoxia in the tenogenic differentiation of MSCs in vitro and in vivo and to compare the tenogenic differentiation capacities of different MSCs under hypoxia condition in vitro. Methods: Adipose tissue-derived MSCs (AMSCs) and bone marrow-derived MSCs (BMSCs) were isolated and characterized by the expression of MSC-specific markers and tri-lineage differentiation. The expression of hypoxia induced factor-1 alpha (Hif-1α) and the proliferation of AMSCs and BMSCs were examined in order to confirm the establishment of hypoxia condition. qRT-PCR, western blot, and immunofluorescence staining were used to evaluate the expression of tendon-associated marker Col-1a1, Col-3a1, Dcn, and Tnmd in AMSCs and BMSCs under hypoxia and/or Tgf-β1 condition. In vivo, a patellar tendon injury model was established. Normoxic and hypoxic BMSCs were cultured and implanted. Histological, biomechanical and transmission electron microscopy analyses were performed to assess the improved healing effect of hypoxic BMSCs on tendon injury. Results: Hypoxia remarkably increased the expression of Hif-1α and the proliferation of AMSCs and BMSCs. Our in vitro results detected that hypoxia not only promoted a significant increase in tenogenic markers in both AMSCs and BMSCs compared with the normoxia group, but also showed higher inductility compared with Tgf-β1. In addition, hypoxic BMSCs exhibited higher potential of tenogenic differentiation than hypoxic AMSCs. Our in vivo results demonstrated that hypoxic BMSCs possessed better histological and biomechanical properties than those of normoxic BMSCs, as evidenced by histological scores, quantitative analysis of immunohistochemical staining for Col-1a1 and Tnmd, the range and average of collagen fibril diameters and patellar tendon biomechanical tests. Conclusions: These findings suggested that hypoxia may be a practical and reliable strategy to induce tenogenic differentiation of BMSCs for tendon repair and could enhance the effectiveness of MSCs therapy in treating tendon injury.

scholarly journals Hypoxia-Induced Mesenchymal Stem Cells Exhibit Stronger Tenogenic Differentiation Capacities and Promote Patellar Tendon Repair in Rabbits

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Guanyin Chen ◽  
Wangqian Zhang ◽  
Kuo Zhang ◽  
Shuning Wang ◽  
Yuan Gao ◽  
...  
Keyword(s):  
Patellar Tendon ◽  
Tendon Repair ◽  
Biomechanical Properties ◽  
Clinical Results ◽  
Medical Problem ◽  
Tendon Injury ◽  
Tenogenic Differentiation ◽  
Tgf Β1

Tendon injury is a common but tough medical problem. Unsatisfactory clinical results have been reported in tendon repair using mesenchymal stem cell (MSC) therapy, creating a need for a better strategy to induce MSCs to tenogenic differentiation. This study was designed to examine the effect of hypoxia on the tenogenic differentiation of different MSCs and their tenogenic differentiation capacities under hypoxia condition in vitro and to investigate the in vivo inductility of hypoxia in tenogenesis. Adipose tissue-derived MSCs (AMSCs) and bone marrow-derived MSCs (BMSCs) were isolated and characterized. The expression of hypoxia-induced factor-1 alpha (Hif-1α) was examined to confirm the establishment of hypoxia condition. qRT-PCR, western blot, and immunofluorescence staining were used to evaluate the expression of tendon-associated marker Col-1a1, Col-3a1, Dcn, and Tnmd in AMSCs and BMSCs under hypoxia condition, compared with Tgf-β1 induction. In vivo, a patellar tendon injury model was established. Normoxic and hypoxic BMSCs were cultured and implanted. Histological, biomechanical, and transmission electron microscopy analyses were performed to assess the improved healing effect of hypoxic BMSCs on tendon injury. Our in vitro results showed that hypoxia remarkably increased the expression of Hif-1α and that hypoxia not only promoted a significant increase in tenogenic markers in both AMSCs and BMSCs compared with the normoxia group but also showed higher inductility compared with Tgf-β1. In addition, hypoxic BMSCs exhibited higher potential of tenogenic differentiation than hypoxic AMSCs. Our in vivo results demonstrated that hypoxic BMSCs possessed better histological and biomechanical properties than normoxic BMSCs, as evidenced by histological scores, patellar tendon biomechanical parameters, and the range and average of collagen fibril diameters. These findings suggested that hypoxia may be a practical and reliable strategy to induce tenogenic differentiation of BMSCs for tendon repair and could enhance the effectiveness of MSCs therapy in treating tendon injury.

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