scholarly journals Oxo-M and 4-PPBP Delivery via Multi-Domain Peptide Hydrogel Toward Tendon Regeneration

2021 ◽  
Author(s):  
Ga Young Park ◽  
Solaiman Tarafder ◽  
Samantha Lewis ◽  
Soomin Park ◽  
Ryunhyung Park ◽  
...  

AbstractWe have recently identified novel small molecules, Oxo-M and 4-PPBP, which specifically stimulates endogenous tendon stem/progenitor cells (TSCs) leading to potential regenerative healing of fully-transected tendons. Here we investigated an injectable, multi-domain peptide (MDP) hydrogel providing a controlled delivery of the small molecules for regenerative tendon healing. We investigated the release kinetics of Oxo-M and 4-PPBP from MDP hydrogels and the effect of MDP-released small molecules on tenogenic differentiation of TSCs and in vivo tendon healing. In vitro, MDP showed a sustained release of Oxo-M and 4-PPBP and a slower degradation compared to fibrin. In addition, tenogenic gene expression was significantly increased in TSC with MDP-released Oxo-M and 4-PPBP as compared to the fibrin-released. In vivo, MDP releasing Oxo-M and 4-PPBP significantly improved tendon healing, likely associated with prolonged effects of Oxo-M and 4-PPBP on suppression of M1 macrophages and promotion of M2 macrophages. Comprehensive analyses including histomorphology, digital image processing, and modulus mapping with nanoindentation consistently suggested that Oxo-M and 4-PPBP delivered via MDP further improved tendon healing as compared to fibrin-based delivery. In conclusion, MDP delivered with Oxo-M and 4-PPBP may serve as an efficient regenerative therapeutic for in situ tendon regeneration and healing.

Materials ◽  
2019 ◽  
Vol 12 (12) ◽  
pp. 1924 ◽  
Author(s):  
Vojtech Kundrat ◽  
Nicole Cernekova ◽  
Adriana Kovalcik ◽  
Vojtech Enev ◽  
Ivana Marova

Microbial poly(3-hydroxybutyrate) (PHB) has several advantages including its biocompatibility and ability to degrade in vivo and in vitro without toxic substances. This paper investigates the feasibility of electrospun PHB meshes serving as drug delivery systems. The morphology of the electrospun samples was modified by varying the concentration of PHB in solution and the solvent composition. Scanning electron microscopy of the electrospun PHB scaffolds revealed the formation of different morphologies including porous, filamentous/beaded and fiber structures. Levofloxacin was used as the model drug for incorporation into PHB electrospun meshes. The entrapment efficiency was found to be dependent on the viscosity of the PHB solution used for electrospinning and ranged from 14.4–81.8%. The incorporation of levofloxacin in electrospun meshes was confirmed by Fourier-transform infrared spectroscopy and UV-VIS spectroscopy. The effect of the morphology of the electrospun meshes on the levofloxacin release profile was screened in vitro in phosphate-buffered saline solution. Depending upon the morphology, the electrospun meshes released about 14–20% of levofloxacin during the first 24 h. The percentage of drug released after 13 days increased up to 32.4% and was similar for all tested morphologies. The antimicrobial efficiency of all tested samples independent of the morphology, was confirmed by agar diffusion testing.


Author(s):  
M.T. Dentinho ◽  
K. Khazaal ◽  
J.M. Ribeiro ◽  
E.R. Ørskov

By using separated values of kinetics of in situ dry matter (DM) degradation or in vitro gas production (Menke and Steingass, 1988) of leguminosae hays, Khazaal et al, (1993) reported high correlation with intake (r= 0.88; r= 0.79) and in vivo DM digestibility (DMD) (r= 0.94; r= 0.88). The aim of the present study was to extend the range of samples used and compare the ability of the 2 stages in vitro digestibility (Tilley and Terry, 1963), the in situ DM degradation or the gas production techniques to predict daily intake (g DM/ kgW0.75) and in vivo DM digestibility (DMD) of 19 leguminous and graminaceous hays fed to sheep.Three harvesting stages (early bloom EB, mid bloom MB or in seed IS) made from lucerne (Medicago sativa), sweet clover (Melilotus segetalis), Persian clover (Trifolium resupinatum), Rye (Secale cereale), Triticale (Triticale hexaploid), oat (Avena stativa) and a pre-bloom (PB) Italian ryegrass (Lolium multiflorum ). Each hay was fed ad libitum to 4 Merino male sheep and their intake and in vivo DMD recorded. Gas production (ml/ 200 mg DM) or in situ DM degradation (g/ 100 g DM) were determined as described by Khazaal et al, (1993) after 6, 12, 24, 48, 72 or 96 h incubation. Measured gas production or DM degradation values were fitted to the equation p=a+b(l-e-ct)(McDonald, 1981) where p is gas production or DM degradation at time t and a, b and c are constants. For nylon bag the washing loss (soluble fraction) was defined as A, the insoluble but fermentable matter was defined as B=(a+b)-A, and c is the rate of fermentation or degradation (Ørskov and Ryle, 1990).


Author(s):  
Baiyrkhanova A. ◽  
Ismailova A. ◽  
Botabekova T. ◽  
Enin E. ◽  
Semenova Y.

5-Fluorouracil (5-FU)-loaded chitosan (Ch) film for chemotherapy were prepared applying a superhydrophobic surfacebased encapsulation technology. The aim of this study was to develop polymeric film with glutaraldehyde (GA) of controlled drug delivery systems for 5 – fluorouracil (FU) as a model drug for the treatment of proliferative vitreoretinopathy. Polymer film of chitosan and polyvinyl alcohol (PVA in 75:25 ratios were prepared and treated with GA. FTIR spectra of 5-FU, Ch/5-FU and Ch/PVA film loaded 5-FU were studied. Physical characteristics such as thickness and swelling coefficient of the film were performed. The thermal of the Ch/PVA film was studied with thermogravimethric analysis. The drug loading efficiency, film size and chemical compositions of the film loaded drug were confirmed by UV–vis spectrophotometer and Fourier transform infrared spectroscopy. In vitro release kinetics of drug from the polymeric films was investigated to determine the drug release properties. In vivo study of PVR was showed the efficacy and no toxicity of this formulation. Further uses of the film loaded 5 - fluorouracil may provide an efficiency deliverable for ophthalmic administration.


2019 ◽  
Vol 310 ◽  
pp. 82-93 ◽  
Author(s):  
Kaushik Thanki ◽  
Delphine van Eetvelde ◽  
Antonia Geyer ◽  
Juan Fraire ◽  
Remi Hendrix ◽  
...  

2019 ◽  
Vol 20 (12) ◽  
pp. 3002 ◽  
Author(s):  
Raquel Costa-Almeida ◽  
Isabel Calejo ◽  
Manuela E. Gomes

Tendon tissues have limited healing capacity. The incidence of tendon injuries and the unsatisfactory functional outcomes of tendon repair are driving the search for alternative therapeutic approaches envisioning tendon regeneration. Cellular therapies aim at delivering adequate, regeneration-competent cell types to the injured tendon and toward ultimately promoting its reconstruction and recovery of functionality. Mesenchymal stem cells (MSCs) either obtained from tendons or from non-tendon sources, like bone marrow (BM-MSCs) or adipose tissue (ASCs), have been receiving increasing attention over the years toward enhancing tendon healing. Evidences from in vitro and in vivo studies suggest MSCs can contribute to accelerate and improve the quality of tendon healing. Nonetheless, the exact mechanisms underlying these repair events are yet to be fully elucidated. This review provides an overview of the main challenges in the field of cell-based regenerative therapies, discussing the role of MSCs in boosting tendon regeneration, particularly through their capacity to enhance the tenogenic properties of tendon resident cells.


Author(s):  
S. Prasanthi ◽  
M. Vidyavathi

Objective: Currently natural polymers have wide spread importance in fabrication of controlled drug delivery systems. Hence in this study ocimum basilicum mucilage, (OBM) a natural polymer used to know its effect as polymer alone and in combination with HPMC K15M and Guargum in oral in situ floating gel of Valsartan using 3 full level factorial design.Methods: FTIR studies conducted to know major drug polymer interactions. OBM, HPMC K15M and Guargum were chosen as three independent variables and examined at 3 levels for in vitro buoyancy (Y1) and drug release at 10 h (Y2) as responses. By using mathematical model approach formulation variables were quantitatively evaluated, and optimized formulation (VFIG) subjected for in vitro buoyancy, density, pH, in vitro drug release, drug content, gelling capacity and drug release kinetics. In addition VFIG studied for In vivo buoyancy and release kinetics.Results: FTIR studies revealed that excipients were compatible with drug. ANOVA results shown that independent variables have significant effect (p<0.05) on both the responses. Observed responses of optimized formulation (3 % OBM, 0.88 % HPMC and 1.25 % Guar gum) were in good agreement with the experimental values. Results of all in vitro evaluations lies within the limits and drug release kinetics followed non-fickian diffusion mechanism. In vivo buoyancy study in rabbit evidenced floatation for>8 h and in vivo pharmacokinetic study exhibited increased bioavailability of optimized formulation.Conclusion: Prepared VFIG with optimized concentrations of OBM, HPMC K15M and Guargum exploiting as a promising dosage form for enhanced gastric delivery.


2005 ◽  
Vol 57 (2) ◽  
pp. 223-228 ◽  
Author(s):  
O.N. Di Marco ◽  
M.S. Aello ◽  
S. Arias

The in situ dry matter (DM) disappearance of corn silages in two maturity stages (milk grain and half milk line) of known in vivo and in vitro digestibility was determined, with the main purpose of comparing digestibility values with the ruminal disappearance at 24 and 48h of incubation. A secondary goal was the description of their ruminal digestion kinetics, from which the effective degradability was calculated at an assumed passage rate of 4%/h. Data of in vivo, in vitro and in situ degradability at 24 and 48-h were analyzed with a linear model that included as fixed effects the maturity and the methodology of evaluation, and the kinetic data were described by the exponential model of McDonald. There was a significant effect (P<0.05) of methodology in the estimation of digestibility, but not of maturity or interaction maturity × methodology. The in vivo digestibility (52.9%) was not different from the 24-h in situ degradability (55.6%) with numerical values in the range of the effective degradability. The in vitro digestibility (61.6%) was not different from the 48-h in situ degradability (61.9%), being both estimates higher than the in vivo digestibility. The 24-h in situ degradability was a closer estimator of the in vivo digestibility and the 48-h in situ degradability and the in vitro digestibility overestimated the in vivo parameter by 15-20%.


Author(s):  
Maria Rita Citeroni ◽  
Annunziata Mauro ◽  
Maria Camilla Ciardulli ◽  
Miriam Di Mattia ◽  
Mohammad El Khatib ◽  
...  

Regenerative medicine has greatly progressed, but tendon regeneration mechanisms and robust in vitro tendon differentiation protocols remain to be elucidated. Recently, tendon explant co-culture (CO) has been proposed as an in vitro model to recapitulate the microenvironment driving tendon development and regeneration. Here, we explored standardized protocols for production and storage of bioactive tendon-derived secretomes with an evaluation of their teno-inductive effects on ovine amniotic epithelial cells (AECs). Teno-inductive soluble factors were released in culture-conditioned media (CM) only in response to active communication between tendon explants and stem cells (CMCO). Unsuccessful tenogenic differentiation in AECs was noted when exposed to CM collected from tendon explants (CMFT) only, whereas CMCO upregulated SCXB, COL I and TNMD transcripts, in AECs, alongside stimulation of the development of mature 3D tendon-like structures enriched in TNMD and COL I extracellular matrix proteins. Furthermore, although the tenogenic effect on AECs was partially inhibited by freezing CMCO, this effect could be recovered by application of an in vivo-like physiological oxygen (2% O2) environment during AECs tenogenesis. Therefore, CMCO can be considered as a waste tissue product with the potential to be used for the development of regenerative bio-inspired devices to innovate tissue engineering application to tendon differentiation and healing.


2021 ◽  
Vol 33 (11) ◽  
pp. 2579-2588
Author(s):  
Mandeep Kaur ◽  
Aditya Wadhwa ◽  
Vineet Kumar

Nanomaterials of biological origin are very useful for drug delivery applications. The stability, biodegradability and biocompatibility of pectin nanomaterials in the human body make them an effective drug carrier. This review focus on different aspect of synthesis, drug encapsulation, drug release and safety of pectin-based nanomaterials. The nanomaterials can be used for the delivery of different hydrophilic and hydrophobic drugs to various organs. The release kinetics of drug loaded pectin-based nanoparticles can be studied in vitro as well as in vivo. The pectin-based nanomaterials have good pharmaco-kinetics and can ensure controlled drug delivery. However, the toxicity of pectin-based nanomaterials to human body needs to be evaluated carefully before industrial scale application.


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