10 research outputs found
Core-Shell Nanofibrous Scaffold Based on Polycaprolactone-Silk Fibroin Emulsion Electrospinning for Tissue Engineering Applications
The vast domain of regenerative medicine comprises complex interactions between specific cells’ extracellular matrix (ECM) towards intracellular matrix formation, its secretion, and modulation of tissue as a whole. In this domain, engineering scaffold utilizing biomaterials along with cells towards formation of living tissues is of immense importance especially for bridging the existing gap of late; nanostructures are offering promising capability of mechano-biological response needed for tissue regeneration. Materials are selected for scaffold fabrication by considering both the mechanical integrity and bioactivity cues they offer. Herein, polycaprolactone (PCL) (biodegradable polyester) and ‘nature’s wonder’ biopolymer silk fibroin (SF) are explored in judicious combinations of emulsion electrospinning rather than conventional electrospinning of polymer blends. The water in oil (W/O) emulsions’ stability is found to be dependent upon the concentration of SF (aqueous phase) dispersed in the PCL solution (organic continuous phase). The spinnability of the emulsions is more dependent upon the viscosity of the solution, dominated by the molecular weight of PCL and its concentration than the conductivity. The nanofibers exhibited distinct core-shell structure with better cytocompatibility and cellular growth with the incorporation of the silk fibroin biopolymer
In Situ Silver Nanowire Deposited Cross-Linked Carboxymethyl Cellulose: A Potential Transdermal Anticancer Drug Carrier
Recently, a novel
biopolymeric nanocomposite hydrogel comprised of in situ formed silver
nanowires (AgNWs) deposited chemically cross-linked carboxymethyl
cellulose (CMC) has been developed, which demonstrates superior efficacy
as anticancer drug-curcumin carrier. The cross-linked polymer has
been prepared by grafting poly [2-(methacryloyloxy) ethyl trimethylammonium
chloride] on CMC using diethylene glycol dimethacrylate cross-linker.
The nanocomposite hydrogel has the capability to encapsulate both
hydrophobic/hydrophilic transdermal drugs. With variation in reaction
conditions/parameters, several composite materials have been synthesized
and depending on lower swelling/higher cross-linking and greater gel
strength, an optimized grade of nanocomposite hydrogel has been selected.
The developed nanocomposite hydrogel is characterized with FTIR/NMR
spectra, FESEM/XRD/TGA/AFM/XPS analyses, and UV–visible spectroscopy.
Rheological study has been performed to enlighten the gel strength
of the composite material. The synthesized nanocomposite hydrogel
is biodegradable and nontoxic to mesenchymal stem cells (hMSCs). In
vitro release of curcumin suggests that in situ incorporation of AgNWs
on cross-linked CMC enhanced the penetration power of nanocomposite
hydrogel and released the drug in sustained way (∼62% for curcumin
released in 4 days). Ex vivo rat skin permeation study confirms that
the drug from both the cross-linked and nanocomposite hydrogel was
permeable through the rat skin in controlled fashion. Additionally
the curcumin loaded composite hydrogel can efficiently kill the MG
63 cancer cells, which has been confirmed by apoptosis study and therefore,
probably be a suitable carrier for curcumin delivery toward cancer
cells
Impact of styrene maleic anhydride (SMA) based hydrogel on rat fallopian tube as contraceptive implant with selective antimicrobial property
Chitosan Derivatives Cross-Linked with Iodinated 2,5-Dimethoxy-2,5-dihydrofuran for Non-Invasive Imaging
Radiopaque
polymer derivatives were successfully prepared through
surface diffusion mediated cross-linking of chitosan with iodinated
2,5-dimethoxy-2,5-dihydrofuran. The incorporation of iodine in 2,5-dimethoxy-2,5-dihydrofuran
was validated by <sup>1</sup>H NMR and mass spectroscopy. The cross-linking
of the glucosamine moieties of chitosan with the iodinated product
was confirmed by <sup>13</sup>C NMR and energy-dispersive X-ray spectroscopy.
Radiography analysis proved inherent opacity of the iodinated fibrous
sheets and microspheres that were comparable to the X-ray visibility
of aluminum hollow rings of equivalent thickness and commercially
available radiopaque tape, respectively. Microscopic studies evidenced
retention of the fiber/microsphere morphology after the iodination/cross-linking
reactions. The effects of iodination/cross-linking on the mechanical
and biodegradation properties of fibers were studied by nanoindentation
and enzymatic assay, respectively. In vitro and in vivo studies established
the nontoxic, biodegradable nature of radiopaque derivatives. Iodinated
fiber mesh implanted in a rabbit model was significantly X-ray opaque
compared to the uncross-linked fiber mesh and medical grade surgical
swabs. Further, opacity of the iodinated mesh was evident even after
60 days, though the intensity was reduced, which indicates the biodegradable
nature of the iodinated polymer. The opacity of the iodinated sutures
was also established in the computed tomography images. Finally, the
sufficient in vivo contrast property of the radiopaque microspheres
in the gastrointestinal tract indicates its possible role in clinical
diagnostics
Oleoyl-Chitosan-Based Nanofiber Mats Impregnated with Amniotic Membrane Derived Stem Cells for Accelerated Full-Thickness Excisional Wound Healing
Wound
healing management is a major challenge for critical full-thickness
skin wounds. Development of nanofibrous scaffolds with tunable wettability,
degradation, and biocompatibility are highly desirable. Herein, we
demonstrated synthesis of oleoyl chitosan (OC) by grafting monounsaturated
fatty acid residue, C<sub>18</sub> oleoyl chain, to the backbone of
chitosan molecule and blending with gelatin to form the nanofiber
mats. The physicochemical properties of the nanofiber mats revealed
mechanical strength, moderate surface wettability, and suitable degradation
rate. The nanofibrous mats showed excellent in vitro cytocompatibility
with human amniotic membrane-derived stem cells (HAMSCs) in terms
of enhanced adhesion and proliferation owing to biomimetic nanoarchitecture
and chemical cues. Furthermore, the fabricated nanofiber was implanted
with and without preseeded HAMSCs in the full-thickness wound to evaluate
the skin wound healing efficacy in a rat model. Histological and immunohistochemical
studies were conducted to evaluate the plausible changes of tissue
architecture and expression of molecular markers involved in wound
healing process. Both acellular and HAMSCs incorporated cellular nanofibers
promoted wound contraction remarkably with superior skin tissue regeneration
in terms of enhanced collagen synthesis, re-epithelialization and
initiation of epithelial cells stratification compared to control
group
Treatment of monogenic and digenic dominant genetic hearing loss by CRISPR-Cas9 ribonucleoprotein delivery in vivo
Abstract Mutations in Atp2b2, an outer hair cell gene, cause dominant hearing loss in humans. Using a mouse model Atp2b2 Obl/+, with a dominant hearing loss mutation (Oblivion), we show that liposome-mediated in vivo delivery of CRISPR-Cas9 ribonucleoprotein complexes leads to specific editing of the Obl allele. Large deletions encompassing the Obl locus and indels were identified as the result of editing. In vivo genome editing promotes outer hair cell survival and restores their function, leading to hearing recovery. We further show that in a double-dominant mutant mouse model, in which the Tmc1 Beethoven mutation and the Atp2b2 Oblivion mutation cause digenic genetic hearing loss, Cas9/sgRNA delivery targeting both mutations leads to partial hearing recovery. These findings suggest that liposome-RNP delivery can be used as a strategy to recover hearing with dominant mutations in OHC genes and with digenic mutations in the auditory hair cells, potentially expanding therapeutics of gene editing to treat hearing loss