scholarly journals α2-Macroglobulin-Rich Serum As a Master Inhibitor of Inflammatory Factors Attenuates Cartilage Degeneration in a Mini Pig Model of Osteoarthritis Induced By “Idealized” Anterior Cruciate Ligament Reconstruction

2021 ◽  
Author(s):  
Ruipeng Zhao ◽  
Xiaochun Wei ◽  
Chengming Zhang ◽  
Hongru Wu ◽  
Chuan Xiang ◽  
...  
Keyword(s):  
Anterior Cruciate Ligament ◽  
Cruciate Ligament ◽  
Cartilage Degeneration ◽  
Mature Female ◽  
Inflammatory Factors ◽  
Post Surgery ◽  
Α2 Macroglobulin ◽  
Anterior Cruciate

Abstract Background: α2-Macroglobulin (α2M) is important for chondral protection in post-traumatic osteoarthritis (PTOA). However, its injection into xenogeneic joint cavities has safety hazards, limiting clinical applications. Exploring serum α2M-enriching strategies and the therapeutic effect and mechanism of α2M-rich serum (α2MRS) autologous joint injection to treat PTOA has significant value.Methods: A unique filtration process was used to concentrate α2M from serum. Human osteoarthritic chondrocytes induced with interleukin (IL)-1β were used to evaluate catabolic enzymes, cell proliferation, apoptosis, and gene expression 24h after α2MRS treatment. Eighteen mature female mini pigs were randomized to three groups, sham (n = 6), “idealized” anterior cruciate ligament autograft reconstruction (IACL-R) (n = 6), and IACL-R+α2MRS (n = 6). Expression of inflammatory factors in the synovial fluid (SF) was measured using Luminex assays. Gait features were recorded using the Tekscan Walkway system. The extent of PTOA progression was evaluated using imaging, real-time PCR , and histology 3 months post-surgery.Results: The α2M concentration in α2MRS was higher than that in human and mini pig serum, respectively. In vitro, α2MRS significantly promoted human chondrocyte proliferation (p < 0.001) and reduced apoptosis (p < 0.001) and chondrocyte catabolic cytokine gene transcription (p < 0.001) and secretion (p < 0.001). In vivo, SF concentrations of all tested inflammatory factors were significantly lower in the IACL-R+α2MRS group than in the IACL-R group (p < 0.001). All gait parameters in the IACL-R+α2MRS group returned to normal significantly early compared to those in the IACL-R group (p < 0.05). Imaging , histology, and biochemistry data showed that cartilage degeneration in the IACL-R+α2MRS group was significantly diminished relative to that in the IACL-R group (p < 0.001).Conclusion: Injecting α2MRS into the joint cavity after IACL-R can significantly delay articular cartilage degeneration.

In-Vivo Force Estimation of the Anterior Cruciate Ligament

2009 ◽  
Author(s):  
Ali Hosseini ◽  
Thomas J. Gill ◽  
Guoan Li
Keyword(s):  
Anterior Cruciate Ligament ◽  
Cruciate Ligament ◽  
Acl Injury ◽  
Force Estimation ◽  
Non Invasive ◽  
Injury Mechanisms ◽  
Invasive Method ◽  
Anterior Cruciate

The knowledge of in-vivo ACL forces is instrumental for understanding ACL injury mechanisms and for improving surgical ACL reconstruction techniques. Several in-vitro investigations have measured ACL forces in response to various loads applied to the knee. However, in-vivo ACL forces in response to controlled loading are still unknown. The objective of this study was to estimate the force of healthy ACL as well as the possible upper bound of ACL forces under an increasing axial tibial loading in living subjects using a non-invasive method.

REGENERATION OF ANTERIOR CRUCIATE LIGAMENT WITH SILK-BASED SCAFFOLD IN PORCINE MODEL

2015 ◽  
Vol 15 (01) ◽  
pp. 1550006 ◽  
Author(s):  
ZHENG LI ◽  
JIANKANG HE ◽  
XIANG LI ◽  
WEIGUO BIAN ◽  
WENYOU ZHANG ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Anterior Cruciate Ligament ◽  
Porcine Model ◽  
Cruciate Ligament ◽  
Silk Fibers ◽  
Bone Interface ◽  
Anterior Cruciate ◽  
Large Animals

Silk was widely investigated as a promising scaffold material in ligament tissue engineering. Although a variety of silk scaffolds were developed for the regeneration of anterior cruciate ligament (ACL) in vitro and in vivo, more investigations should be performed in large animals to translate these findings into clinical applications. The aim of this study is to evaluate the feasibility of using silk-based ACL scaffolds to regenerate damaged ACLs in porcine model. The microstructural organization, tissue regeneration as well as ligament-bone interface of silk implants were evaluated with scanning electron microscopy, micro-computerized tomography, histological and immunohistochemical staining at three and six months postoperatively. The results demonstrated that silk fibers in the ACL scaffolds organized in parallel similar with collagen fibers in native ligaments, which facilitated and guided the penetration of newly regenerated tissue into the pores among silk fibers. Collagen production especially collagen I in silk implants significantly increased from three to six months, and was gradually close to the level of native ligaments. At implant-bone interface, indirect ligament-bone insertion was observed at three months and substantial Sharpey's fibers formed at six months. The results indicated that the silk-based ACL scaffold provides a promising tissue engineering approach for ACL regeneration.

Silk fibroin coating through EDC/NHS crosslink is an effective method to promote graft remodeling of a polyethylene terephthalate artificial ligament

2019 ◽  
Vol 33 (10) ◽  
pp. 1407-1414 ◽  
Author(s):  
Jiangyu Cai ◽  
Li Zhang ◽  
Jun Chen ◽  
Shiyi Chen
Keyword(s):  
Anterior Cruciate Ligament ◽  
Anterior Cruciate Ligament Reconstruction ◽  
Polyethylene Terephthalate ◽  
Silk Fibroin ◽  
Ligament Reconstruction ◽  
Cruciate Ligament ◽  
Cruciate Ligament Reconstruction ◽  
Anterior Cruciate

Anterior cruciate ligament reconstruction using polyethylene terephthalate artificial ligaments is one of the research hotspots in sports medicine but it is still challenging to achieve biological healing. The purpose of this study was to modify polyethylene terephthalate ligament with silk fibroin through ethyl-3–(3-dimethylaminopropyl)carbodiimide (EDC)/N-hydroxysuccinimide (NHS) crosslink and to investigate the performance of graft remodeling in vitro and in vivo. After silk fibroin coating, changes in the surface properties of ligament were characterized by scanning electron microscopy, attenuated total reflectance-Fourier transform infrared spectroscopy and water contact angle measurements. The compatibility of polyethylene terephthalate ligament with silk fibroin coating was investigated in vitro. The results showed the silk fibroin coating significantly improved adhesion, proliferation and extracellular matrix secretion of fibroblast cells. Moreover, a rabbit anterior cruciate ligament reconstruction model was established to evaluate the effect of ligament with silk fibroin coating in vivo. The gross observation and histological results showed that the silk fibroin coating significantly inhibited inflammation response and promoted new tissue regeneration with fusiform cells infiltration in and around the graft. Furthermore, the expressions of collagen I protein and mRNA in the silk fibroin-coated polyethylene terephthalate group were much higher than those in the control group according to the immunohistochemical and real-time polymerase chain reaction results. Therefore, silk fibroin coating through EDC/NHS crosslink promotes the biocompatibility and remodeling process of polyethylene terephthalate artificial ligament in vitro and in vivo. It can be considered as a potential solution to the problem of poor remodeling of artificial ligaments after anterior cruciate ligament reconstruction in the clinical applications.

Does Graft Construct Lengthening at the Fixations Cause an Increase in Anterior Laxity Following Anterior Cruciate Ligament Reconstruction in vivo?

2010 ◽  
Vol 132 (8) ◽  
Author(s):  
Conrad K. Smith ◽  
M. L. Hull ◽  
S. M. Howell
Keyword(s):  
Anterior Cruciate Ligament ◽  
Cruciate Ligament ◽  
Bone Tunnel ◽  
Anterior Cruciate Ligament Graft ◽  
Potential Increase ◽  
Anterior Laxity ◽  
Fresh Frozen ◽  
Anterior Cruciate

A millimeter-for-millimeter relation between an increase in length of an anterior cruciate ligament graft construct and an increase in anterior laxity has been demonstrated in multiple in vitro studies. Based on this relation, a 3 mm increase in length of the graft construct following surgery could manifest as a 3 mm increase in anterior laxity in vivo, which is considered clinically unstable. Hence, the two primary objectives were to determine whether the millimeter-for-millimeter relation exists in vivo for slippage-resistant fixation of a soft-tissue graft and, if it does not exist, then to what extent the increase in stiffness caused by biologic healing of the graft to the bone tunnel offsets the potential increase in anterior laxity resulting from lengthening at the sites of fixation. Sixteen subjects were treated with a fresh-frozen, nonirradiated, nonchemically processed tibialis allograft. Tantalum markers were injected into the graft, fixation devices, and bones. On the day of surgery and at 1, 2, 3, and 4 months, Roentgen stereophotogrammetric analysis was used to compute anterior laxity at 150 N of anterior force and the total slippage from both sites of fixation. A simple linear regression was performed to determine whether the millimeter-for-millimeter relation existed and a springs-in-series model of the graft construct was used to determine the extent to which the increase in stiffness caused by biological healing of the graft to the bone tunnel offset the increase in anterior laxity resulting from lengthening at the sites of fixation. There was no correlation between lengthening at the sites of fixation and the increase in anterior laxity at 1 month (R2=0.0, slope=0.2). Also, the increase in stiffness of the graft construct caused by biologic healing of the graft to the bone tunnel offset 0.7 mm of the 1.5 mm potential increase in anterior laxity resulting from lengthening at the sites of fixation. This relatively large offset of nearly 50% occurred because lengthening at the sites of fixation was small.

Effect of Lubricin Mimetics on the Inhibition of Osteoarthritis in a Rat Anterior Cruciate Ligament Transection Model

2020 ◽  
Vol 48 (3) ◽  
pp. 624-634 ◽  
Author(s):  
Daniel Nemirov ◽  
Yusuke Nakagawa ◽  
Zhexun Sun ◽  
Amir Lebaschi ◽  
Susumu Wada ◽  
...  
Keyword(s):  
Anterior Cruciate Ligament ◽  
Articular Cartilage ◽  
Cruciate Ligament ◽  
Cartilage Degeneration ◽  
Histological Evaluation ◽  
Anterior Cruciate Ligament Transection ◽  
Friction Coefficients ◽  
Anterior Cruciate ◽  
Articular Cartilage Degeneration

Background: Lubricin, a mucinous glycoprotein, plays a chondroprotective role as a constituent of synovial fluid. Structural analogs have been synthesized to mimic the structure and function of native lubricin in an effort to recapitulate this effect with the goal of delaying progression of osteoarthritis (OA). Purpose: To investigate the efficacy of intra-articular injections of lubricin mimetics in slowing or preventing the progression of posttraumatic OA by using a rat anterior cruciate ligament transection model. Study Design: Controlled laboratory design. Methods: Four lubricin mimetics were investigated, differing from one another in their binding orientations and steric interactions. Eighty skeletally mature Sprague-Dawley rats underwent bilateral anterior cruciate ligament transections and were randomly allocated to receive intra-articular injections (50 µL/injection) of 1 of the 4 mimetics in the right knee and equal volumes of saline injection in the contralateral knee (control). All rats were euthanized 8 weeks postoperatively and assessed via biomechanical analysis, which evaluated comparative friction coefficients across the 4 groups, and histological evaluation of articular cartilage, osteophytes, and synovitis. The Osteoarthritis Research Society International (OARSI) histopathological assessment system was used to evaluate the degree of articular cartilage degeneration and osteophytes, while synovitis was assessed through a semiquantitative scoring system. Binding efficacy of the 4 mimetics was assessed in vitro and in vivo through the immunohistochemical localization of polyethylene glycol. Articular cartilage degeneration and synovitis scoring data analyses were performed with generalized estimating equation modeling. Results: Injection of the group 3 mimetic (random 24 + 400 + 30) directly correlated with improved OARSI scores for femoral articular cartilage degeneration when compared with saline-injected contralateral control knees ( P = .0410). No lubricin mimetic group demonstrated statistically significant differences in OARSI scores for tibial articular cartilage degeneration. Injection of the group 4 mimetic (AB 24 + 400 + 30) led to a statistically significant difference in osteophyte OARSI score ( P = .0019). None of the 4 lubricin mimetics injections incited an additive synovial inflammatory response. Immunohistochemical staining substantiated the binding capacity of all 4 mimetics, while in vivo experimentation revealed that the group 1 and 3 mimetics were still retained within the joint 4 weeks after injection. There were no differences in friction coefficients between any pair of groups and no significant trends based on lubricin mimetic structure. Conclusion: We demonstrated that the tribosupplementation of a traumatically injured knee with a specific lubricin structural analog may attenuate the natural progression of OA. Clinical Relevance: The current lack of efficacious clinical options to counter the onset and subsequent development of OA suggests that further investigation into the synthesis and behavior of lubricin analogs could yield novel translational applications.

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