scholarly journals Trypsin Pre‐Treatment Combined With Growth Factor Functionalized Self‐Assembling Peptide Hydrogel Improves Cartilage Repair in Rabbit Model

2019 ◽  
Vol 37 (11) ◽  
pp. 2307-2315 ◽  
Author(s):  
Gustavo Zanotto ◽  
Paul Liebesny ◽  
Myra Barrett ◽  
Hannah Zlotnick ◽  
Alan Grodzinsky ◽  
...  
Theranostics ◽  
2019 ◽  
Vol 9 (23) ◽  
pp. 7072-7087 ◽  
Author(s):  
Lu-Chieh Huang ◽  
Huan-Chih Wang ◽  
Liang-Hsin Chen ◽  
Chia-Yu Ho ◽  
Pei-Hsuan Hsieh ◽  
...  

2021 ◽  
pp. 036354652110217
Author(s):  
Gustavo M. Zanotto ◽  
Paul Liesbeny ◽  
Myra Barrett ◽  
Hannah Zlotnick ◽  
Eliot Frank ◽  
...  

Background: Microfracture augmentation can be a cost-effective single-step alternative to current cartilage repair techniques. Trypsin pretreatment combined with a growth factor–functionalized self-assembling KLD hydrogel (“functionalized hydrogel”) has been shown to improve overall cartilage repair and integration to surrounding tissue in small animal models of osteochondral defects. Hypothesis: Microfracture combined with trypsin treatment and a functionalized hydrogel will improve reparative tissue quality and integration as compared with microfracture alone in an equine model. Study Design: Controlled laboratory study. Methods: Bilateral cartilage defects (15-mm diameter) were created on the medial trochlear ridge of the femoropatellar joints in 8 adult horses (16 defects total). One defect was randomly selected to receive the treatment, and the contralateral defect served as the control (microfracture only). Treatment consisted of 2-minute trypsin pretreatment of the surrounding cartilage, subchondral bone microfracture, and functionalized hydrogel premixed with growth factors (platelet-derived growth factor and heparin-binding insulin-like growth factor 1). After surgery, all horses were subjected to standardized controlled exercise on a high-speed treadmill. Clinical evaluation was conducted monthly, and radiographic examinations were performed at 2, 16, 24, 32, 40, and 52 weeks after defect creation. After 12 months, all animals were euthanized. Magnetic resonance imaging, arthroscopy, gross pathologic evaluation of the joint, histology, immunohistochemistry, and biomechanical analyses were performed. Generalized linear mixed models (with horse as random effect) were utilized to assess outcome parameters. When P values were <.05, pairwise comparisons were made using least squares means. Results: Improved functional outcome parameters were observed for the treatment group, even though mildly increased joint effusion and subchondral bone sclerosis were noted on imaging. Microscopically, treatment resulted in improvement of several histologic parameters and overall quality of repaired tissue. Proteoglycan content based on safranin O–fast green staining was also significantly higher in the treated defects. Conclusion: Trypsin treatment combined with functionalized hydrogel resulted in improved microfracture augmentation. Clinical Relevance: Therapeutic strategies for microfracture augmentation, such as those presented in this study, can be cost-effective ways to improve cartilage healing outcomes, especially in more active patients.


Nanoscale ◽  
2017 ◽  
Vol 9 (36) ◽  
pp. 13661-13669 ◽  
Author(s):  
Kiara F. Bruggeman ◽  
Yi Wang ◽  
Francesca L. Maclean ◽  
Clare L. Parish ◽  
Richard J. Williams ◽  
...  

Tissue-specific self-assembling peptide (SAP) hydrogels designed based on biologically relevant peptide sequences have great potential in regenerative medicine.


2020 ◽  
Vol 39 (1) ◽  
pp. 165-176
Author(s):  
Nobuhiro Okuno ◽  
Shuhei Otsuki ◽  
Jo Aoyama ◽  
Kosuke Nakagawa ◽  
Tomohiko Murakami ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 744
Author(s):  
Ijeoma F. Uchegbu ◽  
Jan Breznikar ◽  
Alessandra Zaffalon ◽  
Uche Odunze ◽  
Andreas G. Schätzlein

Commercial topical ocular formulations for hydrophobic actives rely on the use of suspensions or oil in water emulsions and neither of these formulation modalities adequately promote drug penetration into ocular tissues. Using the ocular relevant hydrophobic drug, cyclosporine A (CsA), a non-irritant ocular penetration enhancer is showcased, which may be used for the formulation of hydrophobic actives. The activity of this penetration enhancer is demonstrated in a healthy rabbit model. The Molecular Envelope Technology (MET) polymer (N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan), a self-assembling, micelle-forming polymer, was used to formulate CsA into sterile filtered nanoparticulate eye drop formulations and the stability of the formulation tested. Healthy rabbits were dosed with a single dose of a MET–CsA (NM133) 0.05% formulation and ocular tissues analyzed. Optically clear NM133 formulations were prepared containing between 0.01–0.1% w/v CsA and 0.375–0.75% w/v MET polymer. NM133 0.01%, NM133 0.02% and NM133 0.05% were stable for 28 days when stored at refrigeration temperature (5–6 °C) and room temperature (16–23 °C), but there was evidence of evaporation of the formulation at 40 °C. There was no change in drug content when NM133 0.05% was stored for 387 days at 4 °C. On topical dosing to rabbits, corneal, conjunctival and scleral AUC0–24 levels were 25,780 ng.h g−1, 12,046 ng.h g−1 and 5879 ng.h g−1, respectively, with NM133 0.05%. Meanwhile, a similar dose of Restasis 0.05% yielded lower values of 4726 ng.h/g, 4813 ng.h/g and 1729 ng.h/g for the drug corneal, conjunctival and scleral levels, respectively. NM133 thus delivered up to five times more CsA to the ocular surface tissues when compared to Restasis. The MET polymer was non-irritant up to a concentration of 4% w/v. The MET polymer is a non-irritant ocular penetration enhancer that may be used to deliver hydrophobic drugs in optically clear topical ocular formulations.


1997 ◽  
Vol 68 (5) ◽  
pp. 474-480 ◽  
Author(s):  
Shigeyuki Wakitani ◽  
Kazuhiko Imoto ◽  
Tomoatsu Kimura ◽  
Takahiro Ochi ◽  
Kunio Matsumoto ◽  
...  

2016 ◽  
Vol 5 (6) ◽  
pp. 667-674 ◽  
Author(s):  
Nikolaos Oikonomidis ◽  
Nikolaos Kavantzas ◽  
Laskarina-Maria Korou ◽  
Panagiotis Konstantopoulos ◽  
Vasilios Pergialiotis ◽  
...  
Keyword(s):  

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
He Shuying ◽  
Wu Jie

To determine the effects of heparin-derived oligosaccharides (HDOs) on vascular intimal hyperplasia (IH) in balloon-injured carotid artery and the mechanism involved. The animal model was established by rubbing the endothelia within the common carotid artery (CCA) of male rabbits along with a high-cholesterol diet. The arterial IH was testified by histopathological changes of the CCA. Serum lipids were detected using automated biochemical analysis; Expression of mRNAs corresponding to vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1), scavenger receptor class B type I (SR-BI) and ATP-binding cassette transporter A1 (ABCA-1) were analyzed using reverse transcription polymerase chain reaction assays. Expressions of VEGF, VCAM-1, MCP-1, SR-BI and ABCA-1 proteins were detected by western blotting. Enzyme-linked immunosorbent assays were used to quantify expression levels of VEGF and bFGF. The results implied that administration of HDO significantly inhibited common carotid artery histopathology and restenosis that was induced by balloon injury. Treatment with HDO also significantly decreased mRNA and protein expression levels of VEGF, bFGF, VCAM-1, MCP-1, and SR-BI in the arterial wall, however ABCA-1 expression levels were elevated. HDO treatment led to a reduction in various serum lipids (total cholesterol, triglycerides, high-density and low-density lipoproteins). We concluded that, in a rabbit model, HDO can ameliorate IH and the mechanisms might involved VEGF, bFGF, VCAM-1, MCP-1, SR-BI and ABCA-1.


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