scholarly journals Influence of the Mechanical Environment on the Regeneration of Osteochondral Defects

2021 ◽  
Vol 9 ◽  
Author(s):  
Sarah Davis ◽  
Marta Roldo ◽  
Gordon Blunn ◽  
Gianluca Tozzi ◽  
Tosca Roncada
Keyword(s):  
Articular Cartilage ◽  
Subchondral Bone ◽  
Structural Integrity ◽  
Mechanical Performance ◽  
Cartilage Damage ◽  
Mechanical Stimuli ◽  
Osteochondral Defects ◽  
Mechanical Environment ◽  
Nature Restoration

Articular cartilage is a highly specialised connective tissue of diarthrodial joints which provides a smooth, lubricated surface for joint articulation and plays a crucial role in the transmission of loads. In vivo cartilage is subjected to mechanical stimuli that are essential for cartilage development and the maintenance of a chondrocytic phenotype. Cartilage damage caused by traumatic injuries, ageing, or degradative diseases leads to impaired loading resistance and progressive degeneration of both the articular cartilage and the underlying subchondral bone. Since the tissue has limited self-repairing capacity due its avascular nature, restoration of its mechanical properties is still a major challenge. Tissue engineering techniques have the potential to heal osteochondral defects using a combination of stem cells, growth factors, and biomaterials that could produce a biomechanically functional tissue, representative of native hyaline cartilage. However, current clinical approaches fail to repair full-thickness defects that include the underlying subchondral bone. Moreover, when tested in vivo, current tissue-engineered grafts show limited capacity to regenerate the damaged tissue due to poor integration with host cartilage and the failure to retain structural integrity after insertion, resulting in reduced mechanical function. The aim of this review is to examine the optimal characteristics of osteochondral scaffolds. Additionally, an overview on the latest biomaterials potentially able to replicate the natural mechanical environment of articular cartilage and their role in maintaining mechanical cues to drive chondrogenesis will be detailed, as well as the overall mechanical performance of grafts engineered using different technologies.

scholarly journals Genetic Deletion of Interleukin-15 Is Not Associated with Major Structural Changes Following Experimental Post-Traumatic Knee Osteoarthritis in Rats

2021 ◽  
Vol 11 (15) ◽  
pp. 7118
Author(s):  
Ermina Hadzic ◽  
Garth Blackler ◽  
Holly Dupuis ◽  
Stephen James Renaud ◽  
Christopher Thomas Appleton ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Subchondral Bone ◽  
Structural Changes ◽  
Cartilage Damage ◽  
Wild Type ◽  
Significant Difference ◽  
Post Traumatic ◽  
Interleukin 15 ◽  
Joint Trauma ◽  
Surgically Induced

Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease, leading to articular cartilage breakdown, osteophyte formation, and synovitis, caused by an initial joint trauma. Pro-inflammatory cytokines increase catabolic activity and may perpetuate inflammation following joint trauma. Interleukin-15 (IL-15), a pro-inflammatory cytokine, is increased in OA patients, although its roles in PTOA pathophysiology are not well characterized. Here, we utilized Il15 deficient rats to examine the role of IL-15 in PTOA pathogenesis in an injury-induced model. OA was surgically induced in Il15 deficient Holtzman Sprague-Dawley rats and control wild-type rats to compare PTOA progression. Semi-quantitative scoring of the articular cartilage, subchondral bone, osteophyte size, and synovium was performed by two blinded observers. There was no significant difference between Il15 deficient rats and wild-type rats following PTOA-induction across articular cartilage damage, subchondral bone damage, and osteophyte scoring. Similarly, synovitis scoring across six parameters found no significant difference between genetic variants. Overall, IL-15 does not appear to play a key role in the development of structural changes in this surgically-induced rat model of PTOA.

scholarly journals Tissue Modification of the Lateral Compartment of the Tibio-Femoral Joint Following In Vivo Varus Loading in the Rat

2012 ◽  
Vol 134 (10) ◽  
Author(s):  
M. L. Roemhildt ◽  
B. D. Beynnon ◽  
M. Gardner-Morse ◽  
K. Anderson ◽  
G. J. Badger
Keyword(s):  
Articular Cartilage ◽  
Subchondral Bone ◽  
Compressive Loading ◽  
Compressive Load ◽  
Lateral Compartment ◽  
Peripheral Region ◽  
Degenerative Changes ◽  
Medial Compartment ◽  
Compressive Loads

This study describes the first application of a varus loading device (VLD) to the rat hind limb to study the role of sustained altered compressive loading and its relationship to the initiation of degenerative changes to the tibio-femoral joint. The VLD applies decreased compressive load to the lateral compartment and increased compressive load to the medial compartment of the tibio-femoral joint in a controlled manner. Mature rats were randomized into one of three groups: unoperated control, 0% (sham), or 80% body weight (BW). Devices were attached to an animal’s leg to deliver altered loads of 0% and 80% BW to the experimental knee for 12 weeks. Compartment-specific material properties of the tibial cartilage and subchondral bone were determined using indentation tests. Articular cartilage, calcified cartilage, and subchondral bone thicknesses, articular cartilage cellularity, and degeneration score were determined histologically. Joint tissues were sensitive to 12 weeks of decreased compressive loading in the lateral compartment with articular cartilage thickness decreased in the peripheral region, subchondral bone thickness increased, and cellularity of the midline region decreased in the 80% BW group as compared to the 0% BW group. The medial compartment revealed trends for diminished cellularity and aggregate modulus with increased loading. The rat-VLD model provides a new system to evaluate altered quantified levels of chronic in vivo loading without disruption of the joint capsule while maintaining full use of the knee. These results reveal a greater sensitivity of tissue parameters to decreased loading versus increased loading of 80% BW for 12 weeks in the rat. This model will allow future mechanistic studies that focus on the initiation and progression of degenerative changes with increased exposure in both magnitude and time to altered compressive loads.

A Novel Experimental Technique for Quantifying the Local Mechanical Environment of Skeletal Tissues

2007 ◽  
Author(s):  
Kristy T. S. Palomares ◽  
Gregory J. Miller ◽  
Louis C. Gerstenfeld ◽  
Thomas A. Einhorn ◽  
Elise F. Morgan
Keyword(s):  
Experimental Technique ◽  
Tissue Level ◽  
Biological Processes ◽  
Mechanical Stimuli ◽  
Mechanical Environment ◽  
Organ Level ◽  
Shear Motion ◽  
Healing Bone ◽  
Tissue Material

A growing body of evidence indicates that mechanical cues modulate the development and repair of skeletal tissues by regulating gene expression and tissue differentiation.[1–3] Further understanding of how the mechanical environment modulates these biological processes could be applied to enhance skeletal repair following injury or disease. Bone healing provides an excellent in vivo system for investigating cellular responses to mechanical stimuli, due to the recruitment of pluripotent, mechano-sensitive, mesenchymal stem cells. For example, recent studies have shown that bending and/or shear motion applied to a healing bone defect can result in cartilage rather than bone formation.[4,5] However, while different global (i.e. organ level) mechanical stimuli are known to result in different healing outcomes, the specific local (i.e. tissue level) stimuli that promote different tissue fates have yet to be established. Finite element analyses can provide estimates of these local stimuli, yet these analyses require many assumptions regarding tissue material properties and boundary conditions. Our overall goal in this study was to develop an experimental technique for quantifying the distributions of local strains that develop in skeletal tissues during mechanical loading.

scholarly journals Effect of differences in mechanical stress in vivo on the onset and progression of knee osteoarthritis

2021 ◽  
Author(s):  
Kohei Arakawa ◽  
Kei Takahata ◽  
Yuichiro Oka ◽  
Kaichi Ozone ◽  
Sumika Nakagaki ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Bone Formation ◽  
Mechanical Stress ◽  
Compressive Stress ◽  
Subchondral Bone ◽  
Shear Force ◽  
Joint Instability ◽  
Cartilage Degeneration ◽  
Articular Cartilage Degeneration

Objective: The effect of the type of mechanical stress on OA onset has not been clarified. The aim of this study was to establish a new model that reproduces the type and increase and decrease of mechanical stress in vivo and to clarify the differences in the mechanism of knee OA onset and progression among the models. Design: To reproduce the difference in mechanical stress, we used the anterior cruciate ligament transection (ACL-T) model and the destabilization of the medial meniscus (DMM) model. In addition, we created a controlled abnormal tibial translation (CATT) model and a controlled abnormal tibial rotation (CATR) model that suppressed the joint instability of the ACL-T and DMM model, respectively. These four models reproduced the increase and decrease in shear force due to joint instability and compressive stress due to meniscal dysfunction. We performed joint instability analysis with soft X-ray, micro computed tomography analysis, histological analysis, and immunohistological analysis in 4 and 6 weeks. Results: Joint instability decreased in the CATT and CATR groups. The meniscus deviated in the DMM and CATR groups. Chondrocyte hypertrophy increased in the ACL-T and DMM groups with joint instability. In the subchondral bone, bone resorption was promoted in the ACL-T and CATT groups, and bone formation was promoted in the DMM and CATR groups. Conclusions: Increased shear force causes articular cartilage degeneration and osteoclast activation in the subchondral bone. In contrast, increased compressive stress promotes bone formation in the subchondral bone earlier than articular cartilage degeneration occurs.

scholarly journals Sost deficiency leads to reduced mechanical strains at the tibia midshaft in strain-matched in vivo loading experiments in mice

2018 ◽  
Vol 15 (141) ◽  
pp. 20180012 ◽  
Author(s):  
Laia Albiol ◽  
Myriam Cilla ◽  
David Pflanz ◽  
Ina Kramer ◽  
Michaela Kneissel ◽  
...  
Keyword(s):  
Bone Formation ◽  
Cortical Bone ◽  
Neutralizing Antibodies ◽  
Bone Geometry ◽  
Bone Adaptation ◽  
Mechanical Stimuli ◽  
Mineral Density ◽  
Littermate Control ◽  
Mechanical Environment

Sclerostin, a product of the Sost gene, is a Wnt-inhibitor and thus negatively regulates bone accrual. Canonical Wnt/β-catenin signalling is also known to be activated in mechanotransduction. Sclerostin neutralizing antibodies are being tested in ongoing clinical trials to target osteoporosis and osteogenesis imperfecta but their interaction with mechanical stimuli on bone formation remains unclear. Sost knockout (KO) mice were examined to gain insight into how long-term Sost deficiency alters the local mechanical environment within the bone. This knowledge is crucial as the strain environment regulates bone adaptation. We characterized the bone geometry at the tibial midshaft of young and adult Sost KO and age-matched littermate control (LC) mice using microcomputed tomography imaging. The cortical area and the minimal and maximal moment of inertia were higher in Sost KO than in LC mice, whereas no difference was detected in either the anterior–posterior or medio-lateral bone curvature. Differences observed between age-matched genotypes were greater in adult mice. We analysed the local mechanical environment in the bone using finite-element models (FEMs), which showed that strains in the tibiae of Sost KO mice are lower than in age-matched LC mice at the diaphyseal midshaft, a region commonly used to assess cortical bone formation and resorption. Our FEMs also suggested that tissue mineral density is only a minor contributor to the strain distribution in tibial cortical bone from Sost KO mice compared to bone geometry. Furthermore, they indicated that although strain gauging experiments matched strains at the gauge site, strains along the tibial length were not comparable between age-matched Sost KO and LC mice or between young and adult animals within the same genotype.

An in Situ Dual Indentation and Optimization Method to Determine Mechanical Properties of Articular Cartilage

2007 ◽  
Author(s):  
Jonathan E. Pottle ◽  
J.-K. Francis Suh
Keyword(s):  
Articular Cartilage ◽  
Stress Relaxation ◽  
Structural Integrity ◽  
Reaction Force ◽  
Model Parameters ◽  
Unconfined Compression ◽  
Confined Compression ◽  
Practical Applications

The efficacy of the biphasic poroviscoelastic (BPVE) theory [1] in constitutive modeling of articular cartilage biomechanics is well-established [2–4]. Indeed, this model has been used to simultaneously predict stress relaxation force across confined compression, unconfined compression, and indentation protocols [2,3]. Previous works have also demonstrated success in simultaneously curve-fitting the BPVE model to reaction force and lateral deformation data gathered from stress relaxation tests of articular cartilage in unconfined compression [4]. However, a potential limitation of practical applications of such a successful model is seen in some commonly-employed mechanical testing methods for articular cartilage, such as confined compression and unconfined compression. These methods require the excision of a disk of cartilage from its underlying subchondral base, which likely would compromise the structural integrity of the tissue, causing swelling and curling artifacts of the sample [5]. Indentation represents a testing protocol that can be used with an intact cartilage layer. This results in a specimen more closely resembling cartilage in vivo. Using an agarose gel construct, our previous study [6] has demonstrated that a unique set of the six BPVE model parameters of a soft tissue can be determined readily from in situ dual indentation method using stress relaxation and creep viscoelastic protocols. The objective of the current study is to validate the efficacy of this technique as a means to determine the BPVE material parameters of articular cartilage.

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