scholarly journals Long term outcomes of biomaterial-mediated repair of focal cartilage defects in a large animal model

2021 ◽  
Vol 41 ◽  
pp. 40-51
Author(s):  
ML Sennett ◽  
◽  
JM Friedman ◽  
BS Ashley ◽  
BD Stoeckl ◽  
...  
Keyword(s):  
Animal Model ◽  
Cartilage Repair ◽  
Standard Of Care ◽  
Long Term Results ◽  
Large Animal Model ◽  
Cartilage Defects ◽  
Large Animal ◽  
Long Term Outcomes ◽  
Short Term

The repair of focal cartilage defects remains one of the foremost issues in the field of orthopaedics. Chondral defects may arise from a variety of joint pathologies and left untreated, will likely progress to osteoarthritis. Current repair techniques, such as microfracture, result in short-term clinical improvements but have poor long-term outcomes. Emerging scaffold-based repair strategies have reported superior outcomes compared to microfracture and motivate the development of new biomaterials for this purpose. In this study, unique composite implants consisting of a base porous reinforcing component (woven poly(ε-caprolactone)) infiltrated with 1 of 2 hydrogels (self-assembling peptide or thermo-gelling hyaluronan) or bone marrow aspirate were evaluated. The objective was to evaluate cartilage repair with composite scaffold treatment compared to the current standard of care (microfracture) in a translationally relevant large animal model, the Yucatan minipig. While many cartilage-repair studies have shown some success in vivo, most are short term and not clinically relevant. Informed by promising 6-week findings, a 12-month study was carried out and those results are presented here. To aid in comparisons across platforms, several structural and functionally relevant outcome measures were performed. Despite positive early findings, the long-term results indicated less than optimal structural and mechanical results with respect to cartilage repair, with all treatment groups performing worse than the standard of care. This study is important in that it brings much needed attention to the importance of performing translationally relevant long-term studies in an appropriate animal model when developing new clinical cartilage repair approaches.

scholarly journals Visually guided tube thoracostomy insertion comparison to standard of care in a large animal model

Injury ◽  
2017 ◽  
Vol 48 (4) ◽  
pp. 849-853 ◽  
Author(s):  
Matthew C. Hernandez ◽  
David Vogelsang ◽  
Jeff R. Anderson ◽  
Cornelius A. Thiels ◽  
Gregory Beilman ◽  
...  
Keyword(s):  
Animal Model ◽  
Standard Of Care ◽  
Tube Thoracostomy ◽  
Large Animal Model ◽  
Large Animal ◽  
Visually Guided

Acute, subacute, and long-term evaluation of a novel endovascular occlusion system in a large animal model

2014 ◽  
Vol 85 (6) ◽  
pp. 1026-1032 ◽  
Author(s):  
Anthony Venbrux ◽  
Philippe Gailloud ◽  
Martin G. Radvany ◽  
Leon Rudakov ◽  
Maximilian Y. Emmert ◽  
...  
Keyword(s):  
Animal Model ◽  
Large Animal Model ◽  
Large Animal ◽  
Endovascular Occlusion ◽  
Term Evaluation

scholarly journals 2061 Acellular hyaluronic acid scaffold with growth factor delivery for cartilage repair in a large animal model

2018 ◽  
Vol 2 (S1) ◽  
pp. 3-3
Author(s):  
Anthony R. Martín ◽  
Jay M. Patel ◽  
Hannah M. Zlotnick ◽  
Mackenzie L. Sennet ◽  
James L. Carey ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Animal Model ◽  
Growth Factor ◽  
Cartilage Repair ◽  
Degradation Rate ◽  
Compressive Modulus ◽  
Large Animal Model ◽  
Large Animal ◽  
Growth Factor Release ◽  
Factor Release

OBJECTIVES/SPECIFIC AIMS: Focal cartilage injuries of the knee joint are common and present a treatment challenge due to minimal intrinsic repair. Cartilage tissue engineering techniques currently used in clinical practice are expensive, cumbersome, and often ineffective in patients with mechanical or medical comorbidities. To address these issues, we developed an acellular nanofibrous scaffold with encapsulated growth factors designed to enhanced articular cartilage repair. Our goal is to evaluate this technology in vitro and pilot a large animal model for eventual translation into human subjects. METHODS/STUDY POPULATION: Hyaluronic acid (HA, 65 kDa) will be methacrylated (~40% modification, MeHA) and conjugated with cell-adhesive (RGD) groups. A solution of 4% wt/vol MeHA, 2% wt/vol polyethylene oxide (900 kDa), 0.05% wt/vol Irgacure 2959, and 0.005% wt/vol stromal cell-derived factor-1α (SDF-1α) and/or transforming growth factor-β3 (TGF-β3) will be prepared in ddH2O. The solution will be electrospun onto a rotating mandrel to achieve a dry scaffold thickness of 0.5 mm. The scaffold matt will be UV cross-linked and 5 mm-diameter samples will be cut out. Four groups of scaffolds will be prepared: MeHA, MeHA+SDF, MeHA+TGF, MeHA+SDF+TGF. All groups will be evaluated for fiber diameter, swell thickness, equilibrium compressive modulus, degradation rate, and growth factor release rate over 4 weeks (n=10). Scaffolds will also be seeded with juvenile porcine MSCs (5×104) in 200 μL of medium incubated for 24 hours. Seeded scaffolds will be evaluated for equilibrium compressive modulus, cell infiltration, and chondrogenesis at 4 and 8 weeks (n=10). Scaffolds will then be evaluated in a juvenile Yucatan minipig cartilage defect model. In total, 6 animals will undergo bilateral knee surgery to create four 4 mm-diameter full-thickness cartilage defects in each trochlear grove. All defects will receive microfracture to release marrow elements. Each knee will receive 2 scaffolds of the same group (replicates) with paired microfracture controls, resulting in a sample size of 3. Animals will be sacrificed at 12 weeks and defects will be evaluated via non-destructive indentation testing for mechanical properties, microCT for defect fill and subchondral bone morphology, and histology for ICRS II Visual Histological Assessment Scoring. RESULTS/ANTICIPATED RESULTS: Our preliminary studies have shown reliable replication of electrospun MeHA scaffolds. We anticipate cross-linking density to correlate positively with compressive modulus, and negatively with swell thickness, degradation rate, and growth factor release rate. We anticipate the addition of SDF-1α and TGF-β3 to increase cell infiltration and chondrogenesis, respectively, within seeded scaffolds. Similarly, we expect minipig defects treated with growth factor-releasing scaffolds to show greater mechanical properties, defect fill, and ICRS II score compared with MeHA scaffolds without growth factor. DISCUSSION/SIGNIFICANCE OF IMPACT: This study has the potential to show how an HA-based cell-free scaffold can be augmented with 2 growth factors that act synergistically to improve cartilage repair in a large animal model. This technology would improve upon the cell-free scaffolds already used clinically for autologous matrix-induced chondrogenesis and is directly translatable.

Multi-Tissue, Long-Term Engraftment and Expansion of BCR-ABL-transduced Human Lin-CD34+ Cord Blood Cells in a Large Animal Model.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3265-3265
Author(s):  
Fanyi Zeng ◽  
Mei-Jue Chen ◽  
Zhi-Jian Gong ◽  
Don A. Baldwin ◽  
Hui Qian ◽  
...  
Keyword(s):  
Animal Model ◽  
Cord Blood ◽  
Hematopoietic Cells ◽  
In Utero ◽  
Human Cells ◽  
Laser Scanning Microscopy ◽  
Large Animal Model ◽  
Large Animal ◽  
Wbc Count

Abstract Abstract 3265 Poster Board III-1 In utero transplantation of large animals (sheep and goats) with human hematopoietic cells has proven valuable in distinguishing subsets of human cells with short- and long-term repopulating activity. Transplantation of secondary and tertiary fetal sheep with cells regenerated in primary sheep has also demonstrated the ability of human hematopoietic stem cells to retain and execute their self-renewal potential in a xenogeneic setting. We now describe the novel extension of this approach to the generation of a BCR-ABL gene transfer-based in vivo model of human myeloproliferative disease. Lin-CD34+ human cord blood (CB) cells were transduced with BCR-ABL retrovirus (MSCV-BCR-ABL-IRES-GFP) and the cells were then injected IP into pre-immune fetal goats at 45–55 days of gestation. This induced a high frequency of abortion among the injected fetuses: 79% (n=22) when >5×104BCR-ABL- transduced CB cells were injected as compared to 64% (n=9) when control (MIG)-transduced cells were injected. Six goats transplanted with 2×104 BCR-ABL-transduced cells were born alive and 3 weeks after birth, 3 of these were sacrificed so that their tissues could be analyzed. Interestingly, in the goats injected with BCR-ABL-transduced human cells, only GFP+(BCR-ABL+) human cells were detected and these were found in multiple hematopoietic and non-hematopoietic tissues, including peripheral blood, bone marrow (BM), liver, kidney, lung, heart, and skeletal and smooth muscle (1–49%) by fluorescence microscopy and confocal laser scanning microscopy, FISH and FACS. Immunohistochemical analysis allowed positive cells to also be detected in frozen sections of liver tissue. Continued follow-up of the other recipients of transduced cells showed that the 3 injected with BCR-ABL-transduced cells all developed features of early chronic phase human chronic myeloid leukemia (CML), as evidenced by a 3- to 5-fold elevation in their WBC count (up to 2.5×1010/L as compared to 5–8×109/L in the recipients of MIG-transduced cells, P<0.01). Changes in the WBC count were seen as early as 3 months after birth and up to 2.5 years post-transplant and were accompanied in all 3 of these goats by the presence of GFP+ cells, including human CD34+ stem/progenitor cells, in the blood and BM. Quantitative real-time PCR analysis of genomic DNA from multiple tissues demonstrated up to 8×104 copies of transgene per microgram of DNA. Microarray transcript profiling of blood and liver from BCR-ABL chimeric goats confirmed expression of many human genes, including 321 that were detected at >2.5-fold higher levels in the BCR-ABL chimeric goats as compared to both control chimeric goats and normal human CB. These over-expressed genes are from several functional categories, including tyrosine kinases and other proteins with phosphorylation activities, cell cycle control, cell adhesion, homing and differentiation, transcription, nucleotide binding and ion transport. Several were confirmed by quantitative RT-PCR. These results demonstrate long-term engraftment, but slow expansion of primitive human hematopoietic cells transduced with BCR-ABL fusion gene and transplanted in utero in a large animal model. This novel xenotransplant goat model should be useful for characterizing the early (pre-symptomatic) phase of human CML and for assessing new therapies with potential long-term benefits. Disclosures: No relevant conflicts of interest to declare.

scholarly journals TCT-825 In-Vivo Long Term Evaluation of a Novel Mitral Valve Regurgitation Therapy: Experience in a Preclinical Large Animal Model

2013 ◽  
Vol 62 (18) ◽  
pp. B249
Author(s):  
Athanasios Peppas ◽  
Jon Wilson ◽  
Yanping Cheng ◽  
Christopher Seguin ◽  
Masahiko Shibuya ◽  
...  
Keyword(s):  
Animal Model ◽  
Mitral Valve ◽  
Mitral Valve Regurgitation ◽  
Large Animal Model ◽  
Large Animal ◽  
Valve Regurgitation ◽  
Term Evaluation

scholarly journals A porcine bimicrobial abscess model for testing interventional treatments

2020 ◽  
Author(s):  
Yak-Nam Wang ◽  
Andrew A. Brayman ◽  
Keith T. Chan ◽  
Keith Richmond ◽  
Wayne L. Monsky ◽  
...  
Keyword(s):  
Animal Model ◽  
New Technologies ◽  
Defense Mechanism ◽  
Trauma Surgery ◽  
Standard Of Care ◽  
The Body ◽  
Large Animal Model ◽  
Histological Evaluation ◽  
Large Animal ◽  
Current Standard

AbstractBackgroundAbscess formation is a host defense mechanism to contain the spread of infection. Abscesses can affect any part of the body and are common sequelae to complications of trauma, surgery, systemic infections and other disease states. Most models for abscesses are in small animals. Pursuant to the goal of developing more advanced treatments for abscesses, we sought to develop a large animal model which would reasonably mimic a fluid-filled human abscess.MethodsDomestic swine were inoculated with a bimicrobial mixture of Bacteroides fragilis (B. fragilis) and Escherichia coli (E. coli) supplemented with an irritant (dextran). Inoculations were performed under ultrasound guidance in the muscle, subcutaneously or intradermally within the same animal. Fourteen days after inoculation, lesions were imaged with ultrasound, resected and prepared for histological evaluation.ResultsInjection of bimicrobial (aerobic and anaerobic) bacterial mixtures at multiple sites in a pig produced multiple lesions with histological features similar to encapsulated and multiloculated/multichamber abscesses often observed clinically in humans. Important salient features include the formation of a connective tissue capsule surrounding histologically nearly amorphous pus.ConclusionsThis paper provides the first description of a pig model for multiloculated abscesses. This animal model could potentially enable the evaluation of new technologies to replace or augment the current standard of care (image-guided percutaneous abscess drainage with antibiotics).

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