Extracellular Matrix Mimicking Wound Microenvironment Responsive Amyloid-Heparin@TAAgNP Co-Assembled Hydrogel: An Effective Conductive Antibacterial Wound Healing Material.

Bioengineered composite hydrogel platforms made of a supramolecular coassembly have recently garnered significant attention as promising biomaterial-based healthcare therapeutics. The mechanical durability of amyloids, in conjunction with the structured charged framework rendered by biologically abundant key ECM component glycosaminoglycan, enables us to design minimalistic customized biomaterial suited for stimuli responsive therapy. In this study, by harnessing the heparin sulfate-binding aptitude of amyloid fibrils, we have constructed a pH-responsive extracellular matrix (ECM) mimicking hydrogel matrix. This effective biocompatible platform comprising heparin sulfate-amyloid coassembled hydrogel embedded with polyphenol functionalized silver nanoparticles not only provide a native skin ECM-like conductive environment but also provide wound-microenvironment responsive on-demand superior antibacterial efficacy for effective diabetic wound healing. Interestingly, both the cytocompatibility and antibacterial properties of this bioinspired matrix can be fine-tuned by controlling the mutual ratio of heparin sulfate-amyloid and incubated silver nanoparticle components, respectively. The designed biomaterial platform exhibits notable effectiveness in the treatment of chronic hyperglycemic wounds infected with multidrug-resistant bacteria, because of the integration of pH-responsive release characteristics of the incubated functionalized AgNP and the antibacterial amyloid fibrils. In addition to this, the aforementioned assemblage shows exceptional hemocompatibility with significant antibiofilm and antioxidant characteristics. Histological evidence of the incised skin tissue sections indicates that the fabricated composite hydrogel is also effective in controlling pro-inflammatory cytokines such as IL6 and TNFα expressions at the wound vicinity with significant upregulation of angiogenesis markers like CD31 and α-SMA.

Amyloid-Inspired Engineered Multidomain Amphiphilic Injectable Peptide Hydrogel─An Excellent Antibacterial, Angiogenic, and Biocompatible Wound Healing Material.

The ingrained mechanical robustness of amyloids in association with their fine-tunable physicochemical properties results in the rational design and synthesis of tailor-made biomaterials for specific applications. However, the incredible antimicrobial efficacy of these ensembles has largely been overlooked. This research work provides an insight into the interplay between self-assembly and antimicrobial activity of amyloid-derived peptide amphiphiles and thereby establishes a newfangled design principle toward the development of potent antimicrobial materials with superior wound healing efficacy. Apart from the relationship with many neurodegenerative diseases, amyloids are now considered as an important cornerstone of our innate immune response against pathogenic microbes. Impelled by this observation, a class of amphiphilic antimicrobial peptide-based biomaterial has been designed by taking Aß42 as a template. The designed AMP due to its amphipathic nature undergoes rapid self-assembly to form a biocompatible supramolecular hydrogel network having significant antibacterial as well as wound healing effectivity on both Gram-negative P. aeruginosa and MRSA-infected diabetic wounds via reduced inflammatory response and enhanced angiogenesis. Results suggest that disease-forming amyloids can be used as a blueprint for the fabrication of biomaterial-based antimicrobial therapeutics by fine-tuning both the hydrophobicity of the ß-aggregation prone zone as well as membrane interacting cationic residues.

pH-Responsive Biocompatible Supramolecular Peptide Hydrogel.

Peptide-based hydrogels are highly promising for various biomedical applications owing to their precise self-assembly, biocompatibility, and sensitivity toward biologically relevant external stimuli. Herein, we report pH-responsive self-assembly and gelation of a highly biocompatible amphiphilic peptide PEP-1. This is an octa-peptide and double mutant of a naturally occurring ß-strand peptide fragment of the protein Galectin-1, available in bovine spleen. PEP-1 was synthesized by using the Rink amide resin as the solid support in a homemade apparatus. At pH 7.4, it exhibits spontaneous gelation with very high yield stress of 88.0 Pa and gel-to-sol temperature of 84 °C at C = 2.0 wt %. Microscopy studies revealed entangled fibrillar morphology whereas circular dichroism, Fourier tranform IR, and Thioflavin T assay indicated formation of ß-sheet rich secondary structure. The assembled state was found to be stable in neutral pH whereas either decrease or increase in the pH resulted in disassembly owing to the presence of the pH responsive Asp and Lys residues. The gel network showed ability to entrap water-soluble guest molecules such as Calcein which could be selectively released at acidic pH whereas under neutral condition the release was negligible. MTT assay revealed remarkable biocompatibility of the PEP-1 gel as almost 100% cells were alive after 48 h incubation in the presence of PEP-1 (2.0 mg/mL).

Morphology Regulation in Redox Destructible Amphiphilic Block Copolymers and Impact on Intracellular Drug Delivery.

In two ABA type amphiphilic block copolymers (P1, P2), the hydrophobic B block consists of a bioreducible segmented poly(disulfide) (PDS), while poly-N-isopropylacrylamide (PNIPAM) or poly(triethyleneglycol)methylether-methacrylate (PTEGMA) serve as the hydrophilic A blocks in P1 and P2, respectively, leading to the formation of polymersome and micelle, owing to the difference in the packing parameters. Both exhibit comparable doxorubicin (Dox) encapsulation efficiency, but glutathione (GSH) triggered release appears much faster from the polymersome than micelle owing to the complete degradation of the PDS segment in polymersome morphology unlike in micelle. Dox-loaded polymers (P1-Dox and P2-Dox) exhibit minimum toxicity to normal cells like C2C12. By contrast, P1-Dox shows excellent killing efficiency to the HeLa cells (cancer cell) (in which the GSH concentration is significantly higher). However, P2-Dox reveals a rather poor activity even to HeLa cells. Fluorescence microscopy studies show comparable cellular uptake of P1-Dox and P2-Dox. But the polymersome entrapped dye escapes fast from the cargo and reach the nucleus, while the drug-loaded micelle remains trapped in the perinuclear zone explaining the significant difference in the drug delivery performance of polymersome and micelle.

Fluorescent PEGulated Oligourethane Nanoparticles for Long-Term Cellular Tracing.

We have introduced a new ABA-type amphiphilic block copolymer consisting of functional oligourethane hydrophobic blocks and two polyethylene glycol (PEG) hydrophilic blocks. The polymer was synthesized in a single step by step-growth polymerization between two monomers, namely tetraphenylethylene (TPE)-diol and hexamehylene di-isocyanate in the presence of a monofunctional impurity PEG-2000. The polymer exhibits facile self-assembly in water by synergistic effects of H-bonding and π-π interaction among the oligourethane core, leading to the formation of robust nanoparticles with remarkable aggregation-induced emission (AIE). These nanoparticles show very low critical aggregation concentration, stability over a large pH window, and excellent biocompatibility as revealed by an MTT assay. Cellular imaging with cancer cells showed facile cellular uptake and, more importantly, retention of AIE in cellular milieu for long times, which was successfully utilized for long-term cancer cell tracking.

Hemodynamic response to endotracheal intubation using C-Trach assembly and direct laryngoscopy.

PURPOSE: Our objective was to study the pressor response to endotracheal intubation through laryngeal mask airway C-Trach and compare it to the hemodynamic response to intubation with direct laryngoscopy (DL). MATERIALS AND METHODS: After obtained approval from institutional ethical committee, 100 patients of American Society of Anesthesiologists physical Status I, aged 14-65 years, posted for elective surgery were enrolled in the trial. They were randomly divided into two groups of each 50 patients. Anesthesia technique was standardized and patients of Group I were intubated using DL, while patients of Group II were intubated with the help of C-Trach assembly. Hemodynamic parameters, systemic blood pressure (systolic and diastolic) and heart rate were recorded before and after induction of anesthesia and every minute up to 5 min after intubation. RESULTS: Patients of Group II recorded a minimal rise in peak systolic blood pressure (SBP) (1.8%) and diastolic blood pressure (10.6%). In comparison patients of Group I recorded a significant sustained rise in peak SBP (20.3%) and diastolic blood pressure (21.4%). However heart rate changes recorded in the two groups were of equal measure (peak rise of 22.9% in Group I vs. 22.4% in Group II). CONCLUSION: We conclude that intubation through C-Trach generates a lower pressor response to intubation in comparison to intubation using DL.

A short GC rich DNA derived from microbial origin targets tubulin/microtubules and induces apoptotic death of cancer cells.

A short GC rich DNA derived from microbial origin interacts with tubulin/microtubules activates p53 over expression and induces apoptotic death of human breast cancer (MCF-7) cells.