A short-term evaluation of a thermoplastic polyurethane implant for osteochondral defect repair in an equine model (original) (raw)
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Tri-layered composite plug for the repair of osteochondral defects: in vivo study in sheep
Journal of Tissue Engineering
Cartilage defects are a source of pain, immobility, and reduced quality of life for patients who have acquired these defects through injury, wear, or disease. The avascular nature of cartilage tissue adds to the complexity of cartilage tissue repair or regeneration efforts. The known limitations of using autografts, allografts, or xenografts further add to this complexity. Autologous chondrocyte implantation or matrix-assisted chondrocyte implantation techniques attempt to introduce cultured cartilage cells to defect areas in the patient, but clinical success with these are impeded by the avascularity of cartilage tissue. Biodegradable, synthetic scaffolds capable of supporting local cells and overcoming the issue of poor vascularization would bypass the issues of current cartilage treatment options. In this study, we propose a biodegradable, tri-layered (poly(glycolic acid) mesh/poly(l-lactic acid)-colorant tidemark layer/collagen Type I and ceramic microparticlecoated poly(l-lactic acid)-poly(ε-caprolactone) monolith) osteochondral plug indicated for the repair of cartilage defects. The porous plug allows the continual transport of bone marrow constituents from the subchondral layer to the cartilage defect site for a more effective repair of the area. Assessment of the in vivo performance of the implant was conducted in an ovine model (n = 13). In addition to a control group (no implant), one group received the implant alone (Group A), while another group was supplemented with hyaluronic acid (0.8 mL at 10 mg/mL solution; Group B). Analyses performed on specimens from the in vivo study revealed that the implant achieves cartilage formation within 6 months. No adverse tissue reactions or other complications were reported. Our findings indicate that the porous biocompatible implant seems to be a promising treatment option for the cartilage repair.
Evaluation of multiphase implants for repair of focal osteochondral defects in goats
Biomaterials, 2000
The use of biodegradable sca!olds for articular cartilage repair has been investigated by numerous researchers. The objective of this screening study was to examine how the mechanical and physical properties of four multiphase implants can a!ect the cartilage healing response. Multiphase implant prototypes were prepared using poly(D,L)lactide-co-glycolide as the base material. PGA "bers (FR), 45S5 Bioglass (BG) and medical grade calcium sulfate (MGCS) were used as additives to vary sti!ness and chemical properties. Osteochondral defects (3 mm dia. and 4 mm in depth) were created bilaterally in the medial femoral condyle (high-weight bearing) and the distal medial portion of the patellar groove (low-weight bearing) of 16 Spanish goats. Half of the implants were loaded with autologous costochondral chondrocytes. Defect sites (total n"64, 4 sites/treatment) were randomly treated and allowed to heal for 16 weeks, fully weight bearing. At euthanasia, gross evaluations and biomechanical testing were conducted. Histological sections of the defect sites were stained with H and E, Safranin O/Fast Green or processed to analyze collagen architecture. Sections were semi-quantitatively scored for repair tissue structure. Qualitative evaluations showed that all groups had a high percentage of hyaline cartilage and good bony restoration, with new tissue integrating well with the native cartilage. Gross and histology scoring indicated a signi"cantly higher score for defect healing in the condyle than in the patellar groove, but no di!erence in healing for implant types or addition/omission of cells was found. This investigation demonstrates that focal, osteochondral defects in caprine distal femurs treated with various implant constructs were repaired with hyaline-like cartilage and good underlying bone. The multiphase implants show potential for treatment of osteochondral defects and long-term studies need to be undertaken to con"rm the longevity of the regenerated tissue.
Surgical osteochondral defect repair in the horse—a matter of form or function?
Equine Veterinary Journal, 2020
Focal cartilaginous and osteochondral lesions can have traumatic or chondropathic degenerative origin. The fibrocartilaginous repair tissue that forms naturally, eventually undergoes fibrillation and degeneration leading to further disruption of joint homeostasis. Both types of lesion will therefore eventually lead to activity‐related pain, swelling and decreased mobility and will frequently progress to osteoarthritis. Most attempts at realising cartilage regeneration have so far resulted in cartilage repair (and not regeneration). The aim of this article was to review experimental research on surgical cartilage restoration techniques performed so far in equine models. Currently available surgical options for treatment of osteochondral lesions in the horse are summarised. The experimental validity of equine experimental models is addressed and finally possible avenues for further research are discussed.
CARTILAGE, 2016
ObjectiveTo evaluate a biphasic cartilage repair device (CRD) for feasibility of arthroscopic implantation, safety, biocompatibility, and efficacy for long-term repair of large osteochondral defects.MethodsThe CRD was press-fit into defects (10 mm diameter, 10 mm deep) created in the femoral trochlea of 12 horses. In the contralateral limb, 10 mm diameter full-thickness chondral defects were treated with microfracture (MFX). Radiographs were obtained pre- and postoperatively, and at 4, 12, and 24 months. Repeat arthroscopy was performed at 4 and 12 months. Gross assessment, histology, mechanical testing, and magnetic resonance imaging (MRI) were performed at 24 months.ResultsThe CRD was easily placed arthroscopically. There was no evidence of joint infection, inflammation, or degeneration. CRD-treated defects had significantly more sclerosis compared to MFX early ( P = 0.0006), but was not different at 24 months. CRD had better arthroscopic scores at 4 months compared to MFX ( P = 0...
Osteochondral lesions resulting from osteochondritis dissecans are problematic to treat and present a significant challenge for clinicians. The aims of this study were to investigate the use of a scaffold-assisted microfracture approach, employing a novel, multilayered, collagen-based, osteochondral graft substitute in the treatment of severe osteochondritis dissecans of both lateral femoral trochlear ridges in an equine athlete, and to assess the potential of this novel scaffold to enhance repair of the osteochondral unit. A 15 month-old female filly presented with large osteochondritis dissecans lesions involving both femoral lateral trochlear ridges. After routine arthroscopic debridement and microfracture of the subchondral bone, multilayered osteochondral defect repair scaffolds were implanted into the fragmentation beds in both left and right femoropatellar joints via mini-arthrotomies. Exploratory arthroscopy 5 months postimplantation revealed smooth cartilaginous repair tissue, contiguous with the adjacent cartilage, covering the defect. At 22-month follow up, the filly had no signs of lameness and was exercising at her intended level. Radiographically, although still slightly flattened, the femoral trochlear ridges were smooth, with no evidence of osteoarthritis. Ultrasonographically, the defects were filled with bone and covered with an overlying cartilaginous layer, with the trochlear ridge contour almost entirely restored. This report demonstrates the effective clinical use of this novel, multilayered, osteochondral defect repair scaffold in the treatment of osteochondritis dissecans of an equine athlete. The successful repair achieved here using this novel scaffold in an equine patient with large bilateral lesions shows the potential for clinical translation in the treatment of human patients presenting with osteochondral defects.
Biomaterials, 2006
There has been interest in developing novel biological treatments to repair focal cartilage defects. We have developed a method of forming biphasic constructs (''osteochondral''-type plug) in vitro consisting of cartilaginous tissue, formed on and anchored to the intended articulation surface of a porous ceramic substrate. The purpose of this study was to evaluate the biochemical and biomechanical properties and morphology of in vitro-formed biphasic constructs 3 and 9 months after implantation into 4 mm diameter full thickness osteochondral defects in the trochlear groove of sheep stifles. The implants withstood loading in vivo up to 9 months with evidence of fusion to adjacent native cartilage and fixation by bone ingrowth into the ceramic substrate. The cartilage layer was eroded from those implants that were proud to the joint surface. Control implants (ceramic only) had fibrous tissue on the articulating surface after implantation for 3-4 months. Neither the cellularity nor proteoglycan content of the implanted cartilage, when it remained, changed significantly between 3 and 9 months and the collagen content increased slightly. The elastic equilibrium modulus of the cartilage improved with time with the greatest improvement (10-fold) occurring early during the first 3-4 months after implantation. This study suggests that biphasic constructs may be suitable to repair joint defects as the implants were maintained up to 9 months in sheep. Importantly the mechanical properties of the implanted cartilage improved significantly after implantation suggesting that cartilage can mature in vivo after implantation. The results indicate that further study of this treatment approach is warranted to attempt to overcome the technical surgical difficulties identified in this study. r
Mechanical and Morphological Evaluation of Osteochondral Implants in Dogs
Artificial Organs, 2008
Abstract: The mechanical behavior of osteochondral defects was evaluated in this study with the intention of developing alternative procedures. Cylindrical pins (5.00 mm in diameter and in height) made of pHEMA hydrogel covered ultra-high molecular weight polyethylene (UHMWPE) or β-tricalcium phosphate (β-TCP) matrix were used. Ostoechondral defects were caused in the knees of adult dogs and the evaluation was carried out after a 9-month follow-up period. The mechanical behavior of the implants was evaluated by means of an indentation creep test that showed that the UHMWPE matrix maintained its viscoelastic behavior even after follow-up time, while the β-TCP matrix osteochondral implants presented significant alterations. It is believed that the β-TCP osteochondral implants were unable to withstand the load applied, causing an increase of complacency when compared to the UHMWPE osteochondral implants. Based on micro and macroscopic analysis, no significant wear was observed in either of the osteochondral implants when compared to the controls. However, morphological alterations, with fragmentation indices in the patella, were observed either due to friction with the hydrogel in the first postoperative months or due to forming of a dense conjunctive tissue. This wear mechanism caused on the counterface of the implant (patella) was observed, notwithstanding the osteochondral implant studied.
Tissue Engineering Part A, 2008
The objective of this study was to evaluate an injectable, in situ crosslinkable elastin-like polypeptide (ELP) gel for application to cartilage matrix repair in critically sized defects in goat knees. One cylindrical, osteochondral defect in each of seven animals was filled with an aqueous solution of ELP and a biocompatible, chemical crosslinker, while the contralateral defect remained unfilled and served as an internal control. Joints were sacrificed at 3 (n = 3) or 6 (n = 4) months for MRI, histological, and gross evaluation of features of biomaterial performance, including integration, cellular infiltration, surrounding matrix quality, and new matrix in the defect. At 3 months, ELP-filled defects scored significantly higher for integration by histological and gross grading compared to unfilled defects. ELP did not impede cell infiltration but appeared to be partly degraded. At 6 months, new matrix in unfilled defects outpaced that in ELP-filled defects and scored significantly better for MRI evidence of adverse changes, as well as integration and proteoglycan-containing matrix via gross and histological grading. The ELP-crosslinker solution was easily delivered and formed stable, well-integrated gels that supported cell infiltration and matrix synthesis; however, rapid degradation suggests that ELP formulation modifications should be optimized for longer-term benefits in cartilage repair applications.
Physiological research / Academia Scientiarum Bohemoslovaca, 2007
The potential of novel scaffold containing sodium hyaluronate, type I collagen, and fibrin was investigated in the regeneration of osteochondral defects in miniature pigs. Both autologous chondrocyte-seeded scaffolds and non-seeded scaffolds were implanted into two defects located in the non-weight-bearing zone of the femoral trochlea (defect A was located more distally and medially, defect B was located more proximally and laterally). Control defects were left untreated. Twelve weeks after the operation, the knees were evaluated in vivo using MRI. Six months after the implantation, the defects were analyzed using MRI, histological, and immunohistochemical analysis. In the A defects of chondrocyte-seeded scaffold group, hyaline cartilage and fibrocartilage was formed, containing type II collagen, acidic and neutral glycosaminoglycans while the non-seeded scaffold group was predominantly filled with fibrocartilage. Defects in the control group were predominantly filled with fibrous t...
Novel nanostructured scaffold for osteochondral regeneration: pilot study in horses
2010
The present in vivo preliminary experiment is aimed at testing mechanical and biological behaviour of a new nano-structured composite multilayer biomimetic scaffold for the treatment of chondral and osteochondral defects. The three-dimensional biomimetic scaffold (Fin-Ceramica Faenza S.p.A., Faenza -Italy) was obtained by nucleating collagen fibrils with hydroxyapatite nanoparticles, in two configurations, bi-and tri-layered, to reproduce, respectively, chondral and osteochondral anatomy. Chondral defects (lateral condyle) and deep osteochondral defects medial condyle) were made in the distal epiphysis of the third metacarpal bone of both forelimbs of two adult horses and treated respectively with the chondral and osteochondral grafts. Both animals were euthanised six months follow up. The images obtained at the second look arthroscopy evaluation, performed two months after surgery, demonstrated good filling of the chondral and osteo-chondral defects without any inflammatory reaction around and inside the lesions. At the histological analysis the growth of trabecular bone in the osteochondral lesion was evident. Only in one case, the whole thickness of the osteochondral lesion was filled by fibrocartilaginous tissue. The formation of a tidemark line was evident at the interface with the newly formed bone. Newly formed fibrocartilaginous tissue was present in the area of the chondral defect. Initial alignment of the collagen fibres was recognisable with polarised light in both groups. The results of the present pilot study showed that this novel osteochondral and chondral scaffold may act as a suitable matrix to facilitate orderly regeneration of bone and hyaline-like cartilage. J Bone Joint Surg Am 89(4): 718-726. Zeeman R, Dijkstra PJ, van Wachem PB, et al. 2000; The kinetics of 1,4-butanediol diglycidyl ether crosslinking of dermal sheep collagen. J Biomed Mater Res 51(4): 541-548.