Preclinical Testing of New Hydrogel Materials for Cartilage Repair: Overcoming Fixation Issues in a Large Animal Model

Reinforced hydrogels represent a promising strategy for tissue engineering of articular cartilage. They can recreate mechanical and biological characteristics of native articular cartilage and promote cartilage regeneration in combination with mesenchymal stromal cells. One of the limitations of in vivo models for testing the outcome of tissue engineering approaches is implant fixation. The high mechanical stress within the knee joint, as well as the concave and convex cartilage surfaces, makes fixation of reinforced hydrogel challenging. Methods. Different fixation methods for full-thickness chondral defects in minipigs such as fibrin glue, BioGlue®, covering, and direct suturing of nonenforced and enforced constructs were compared. Because of insufficient fixation in chondral defects, superficial osteochondral defects in the femoral trochlea, as well as the femoral condyle, were examined using press-fit fixation. Two different hydrogels (starPEG and PAGE) were compared by 3D-micro-CT (μCT) analysis as well as histological analysis. Results. Our results showed fixation of below 50% for all methods in chondral defects. A superficial osteochondral defect of 1 mm depth was necessary for long-term fixation of a polycaprolactone (PCL)-reinforced hydrogel construct. Press-fit fixation seems to be adapted for a reliable fixation of 95% without confounding effects of glue or suture material. Despite the good integration of our constructs, especially in the starPEG group, visible bone lysis was detected in micro-CT analysis. There was no significant difference between the two hydrogels (starPEG and PAGE) and empty control defects regarding regeneration tissue and cell integration. However, in the starPEG group, more cell-containing hydrogel fragments were found within the defect area. Conclusion. Press-fit fixation in a superficial osteochondral defect in the medial trochlear groove of adult minipigs is a promising fixation method for reinforced hydrogels. To avoid bone lysis, future approaches should focus on multilayered constructs recreating the zonal cartilage as well as the calcified cartilage and the subchondral bone plate.

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Utilization of Finite Element Analysis for Articular Cartilage Tissue Engineering

Materials ◽

10.3390/ma12203331 ◽

2019 ◽

Vol 12 (20) ◽

pp. 3331 ◽

Cited By ~ 5

Author(s):

Chaudhry R. Hassan ◽

Yi-Xian Qin ◽

David E. Komatsu ◽

Sardar M.Z. Uddin

Keyword(s):

Tissue Engineering ◽

Finite Element Analysis ◽

Finite Element ◽

Articular Cartilage ◽

Material Properties ◽

Cartilage Tissue Engineering ◽

Cartilage Tissue ◽

Scaffold Design ◽

Element Analysis ◽

In Vivo Models

Scaffold design plays an essential role in tissue engineering of articular cartilage by providing the appropriate mechanical and biological environment for chondrocytes to proliferate and function. Optimization of scaffold design to generate tissue-engineered cartilage has traditionally been conducted using in-vitro and in-vivo models. Recent advances in computational analysis allow us to significantly decrease the time and cost of scaffold optimization using finite element analysis (FEA). FEA is an in-silico analysis technique that allows for scaffold design optimization by predicting mechanical responses of cells and scaffolds under applied loads. Finite element analyses can potentially mimic the morphology of cartilage using mesh elements (tetrahedral, hexahedral), material properties (elastic, hyperelastic, poroelastic, composite), physiological loads by applying loading conditions (static, dynamic), and constitutive stress–strain equations (linear, porous–elastic, biphasic). Furthermore, FEA can be applied to the study of the effects of dynamic loading, material properties cell differentiation, cell activity, scaffold structure optimization, and interstitial fluid flow, in isolated or combined multi-scale models. This review covers recent studies and trends in the use of FEA for cartilage tissue engineering and scaffold design.

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Rectangular Recession Trochleoplasty for Treatment of Patellar Luxation in Dogs and Cats

Veterinary and Comparative Orthopaedics and Traumatology ◽

10.1055/s-0038-1632628 ◽

2000 ◽

Vol 13 (01) ◽

pp. 39-43 ◽

Cited By ~ 11

Author(s):

R. L. Goring ◽

J. J. de Haan ◽

K. W. Talcott

Keyword(s):

Articular Cartilage ◽

Surgical Treatment ◽

Subchondral Bone ◽

Surgical Procedure ◽

New Technique ◽

Trochlear Groove ◽

Osteochondral Autograft ◽

Press Fit ◽

A New Technique ◽

Hyaline Articular Cartilage

SummaryTrochleoplasty is a fundamental component of surgical treatment for patients with inadequate trochlear depth associated with patellar luxation. Traditional methods of trochleoplasty include trochlear resection, chondroplasty and wedge recession trochleoplasty. Each technique has its benefits and limitations. Rectangular recession trochleoplasty (RRT) is a new technique that builds upon the strengths of its predecessors while minimizing their limitations. Rectangular recession utilizes a rectangular osteochondral autograft that is harvested from the trochlear groove and replaced into its recipient bed. Unlike wedge recession, the autograft surfaces are compressed and buttressed within the recipient bed. resulting in secure implantation of the autograft. Rectangular recession achieves maximal preservation of hyaline articular cartilage while minimizing exposure of abrasive subchondral bone. Rectangular recession can be performed on dogs and cats as small as 3 kg and has been clinically effective in treating over 100 cases of patellar luxation.Trochleoplasty is an important surgical procedure for treatment of patellar luxation in the dog and cat. The objective of any trochleoplasty technique is to achieve adequate trochlear depth and width while optimizing preservation of hyaline articular cartilage. Rectangular recession trochleoplasty (RRT) is a new technique that achieves adequate trochlear width and depth utilizing a securely “press-fit” osteochondral autograft that achieves maximal preservation of hyaline articular cartilage.

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Effect of oblique headless compression screw fixation for metacarpal shaft fracture: a biomechanical in vitro study

BMC Musculoskeletal Disorders ◽

10.1186/s12891-020-03939-2 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Yung-Cheng Chiu ◽

Tsung-Yu Ho ◽

Yen-Nien Ting ◽

Ming-Tzu Tsai ◽

Heng-Li Huang ◽

...

Keyword(s):

Articular Cartilage ◽

Screw Fixation ◽

Shaft Fracture ◽

Metacarpal Bone ◽

Entry Point ◽

Fixation Method ◽

Exit Point ◽

Compression Screw ◽

Headless Compression Screw ◽

Metacarpal Shaft

Abstract Background Metacarpal shaft fracture is a common fracture in hand trauma injuries. Surgical intervention is indicated when fractures are unstable or involve considerable displacement. Current fixation options include Kirschner wire, bone plates, and intramedullary headless screws. Common complications include joint stiffness, tendon irritation, implant loosening, and cartilage damage. Objective We propose a modified fixation approach using headless compression screws to treat transverse or short-oblique metacarpal shaft fracture. Materials and methods We used a saw blade to model transverse metacarpal neck fractures in 28 fresh porcine metacarpals, which were then treated with the following four fixation methods: (1) locked plate with five locked bicortical screws (LP group), (2) regular plate with five bicortical screws (RP group), (3) two Kirschner wires (K group), and (4) a headless compression screw (HC group). In the HC group, we proposed a novel fixation model in which the screw trajectory was oblique to the long axis of the metacarpal bone. The entry point of the screw was in the dorsum of the metacarpal neck, and the exit point was in the volar cortex of the supracondylar region; thus, the screw did not damage the articular cartilage. The specimens were tested using a modified three-point bending test on a material testing system. The maximum fracture forces and stiffness values of the four fixation types were determined by observing the force–displacement curves. Finally, the Kruskal–Wallis test was adopted to process the data, and the exact Wilcoxon rank sum test with Bonferroni adjustment was performed to conduct paired comparisons among the groups. Results The maximum fracture forces (median ± interquartile range [IQR]) of the LP, RP, HC, and K groups were 173.0 ± 81.0, 156.0 ± 117.9, 60.4 ± 21.0, and 51.8 ± 60.7 N, respectively. In addition, the stiffness values (median ± IQR) of the LP, HC, RP, and K groups were 29.6 ± 3.0, 23.1 ± 5.2, 22.6 ± 2.8, and 14.7 ± 5.6 N/mm, respectively. Conclusion Headless compression screw fixation provides fixation strength similar to locked and regular plates for the fixation of metacarpal shaft fractures. The headless screw was inserted obliquely to the long axis of the metacarpal bone. The entry point of the screw was in the dorsum of the metacarpal neck, and the exit point was in the volar cortex of the supracondylar region; therefore the articular cartilage iatrogenic injury can be avoidable. This modified fixation method may prevent tendon irritation and joint cartilage violation caused by plating and intramedullary headless screw fixation.

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Arthroscopic Articular Cartilage Scores of the Canine Stifle Joint with Naturally Occurring Cranial Cruciate Ligament Disease

Veterinary and Comparative Orthopaedics and Traumatology ◽

10.1055/s-0040-1719064 ◽

2020 ◽

Author(s):

Kimberly A. Agnello ◽

Kei Hayashi ◽

Dorothy Cimino Brown

Keyword(s):

Articular Cartilage ◽

Cruciate Ligament ◽

Cartilage Damage ◽

Meniscal Tear ◽

Trochlear Groove ◽

Cranial Cruciate Ligament ◽

Stifle Joint ◽

Naturally Occurring ◽

Medial Meniscal Tear ◽

Severity Scores

Abstract Objective This study aimed to evaluate frequency, location and severity of cartilage pathology in dogs with naturally occurring cranial cruciate ligament (CCL) disease. Study Design Stifle arthroscopic video recordings (n = 120) were reviewed. A modified Outerbridge classification system (MOCS) (0–4) was used to score cartilage at 10 locations in the femorotibial (medial and lateral femoral condyles and tibial plateaus) and patellofemoral compartments (proximal, middle and distal locations of the patella and femoral trochlear groove) of the stifle joint. Synovial pathology was scored and the presence of a medial meniscal tear was recorded. A Kruskal–Wallis test was used to evaluate association of location and synovitis with cartilage score; and presence of meniscal tear with cartilage and synovitis scores. Bonferroni correction was utilized and p < 0.05 was considered significant. Results Cartilage pathology and synovitis were identified in all joints. Overall cartilage severity scores were low (median MOCS 1). The median MOCS of the proximal trochlear groove (2) was significantly higher than all other locations evaluated. Higher synovitis scores were significantly associated with higher cartilage severity scores and a medial meniscal tear had no association with cartilage severity scores or synovitis. Conclusion Arthroscopic articular cartilage lesions are common in dogs with CCL disease at the time of surgical intervention, although the severity of cartilage damage is mild. The proximal trochlear groove of the femur had the most severe cartilage score in the stifle joint.

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Oligonucleotide Therapies in the Treatment of Arthritis: A Narrative Review

Biomedicines ◽

10.3390/biomedicines9080902 ◽

2021 ◽

Vol 9 (8) ◽

pp. 902

Author(s):

Susanne N. Wijesinghe ◽

Mark A. Lindsay ◽

Simon W. Jones

Keyword(s):

Rheumatoid Arthritis ◽

Articular Cartilage ◽

Joint Diseases ◽

Synovial Joint ◽

Pharmacological Treatments ◽

In Vivo Models ◽

Inflammatory Joint Diseases ◽

Joint Pathology ◽

Cellular Pathways

Osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common chronic inflammatory joint diseases, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. The pathology of both OA and RA involves multiple tissues within the joint, including the synovial joint lining and the bone, as well as the articular cartilage in OA. In this review, we discuss the potential for the development of oligonucleotide therapies for these disorders by examining the evidence that oligonucleotides can modulate the key cellular pathways that drive the pathology of the inflammatory diseased joint pathology, as well as evidence in preclinical in vivo models that oligonucleotides can modify disease progression.

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