Biology subjects

Chaudhry, H.

Publications and source records attributed to Chaudhry, H..

3 recordsLinked to original sources

bioRxiv2024

Anti-fibrotic Effects of Atorvastatin Delivered via Keratin-based Hydrogels

Implantations of degradable biomaterials for drug delivery or restoration and regenerative medicine cause fibrosis and acute inflammation which may lead to chronic side effects. Additionally, the fibrous encapsulation can itself inhibit the local cells from proliferating and forming new healthy tissue. Current drug delivery models require a new method to decrease the adverse effects following implantation of biomaterials in patients and inhibit the activation signaling sent to quiescent fibroblasts. This research details the novel chemical and physical properties of reduced keratin (KTN) hydrogels extracted from residual human hair with sheared cuticle layers, obtained from barbershops and beauty salons. KTN hydrogels with and without calcium ions conjugated with atorvastatin (Ator), which is thought to affect TGF-{beta} signaling pathways directly by competitively inhibiting key signal transmitters and cellular responses, were investigated via electron microscopy, absorbance spectroscopy, and computational modeling and simulation to observe the proliferative inhibition of fibroblastic cells in comparison to the alginate hydrogel controls. Hydrogel extracts were tested for non-cytotoxic effects via L929 adipose fibroblast cell culture following ISO 10993-5 standard for safety of medical device biomaterials. Two cell models were exposed to increasing serial concentrations of Ator to evaluate the half maximal effective concentration (EC50). For quiescent fibroblasts, Ators EC50 was observed at 368 M in PBS. For mesenchymal stem cells (MSCs), Ators EC50 was observed at 209 M in PBS. The mass of drug was normalized in all groups after calculating their timed absorption and release, and KTN hydrogels conjugated with calcium ions and Ator (ATCK) completely absorbed the drug < 0.5 h while KTN hydrogels with Ator alone (ATKR) completely absorbed the drug at 1h. After 7d in PBS, ATCK released Ator at 2.2 {+/-} 0.7% while Ator in calcium alginate spheres (ATLG) was released at 7.8 {+/-} 1.1% and ATKR released 11.2 {+/-} 4.3% of drug. On-going research focuses on other active fibroblastic cell types and in vivo experimentation to observe foreign body response in subcutaneous mouse tissue.

bioengineering↗

bioRxiv2024

Biocompatibility of KAPs-Depleted Residual Hair

This work is an in-depth investigation of the in vitro and in vivo biocompatibility of processed and treated residual human hair samples with intact cuticle layers. The specimens included oxidized hair with no melanin (BLH) and hair with medium-(M-KAP) and low-(L-KAP) levels of keratin associated proteins (KAPs), confirmed through gel electrophoresis, electron microscopy, and trichrome histological staining, in comparison to the untreated regular hair (REG) control. All hair groups, high KAPs (H-KAPs: REG and BLH), M-KAP, and L-KAP, were found to be non-cytotoxic in the adipose fibroblast cell lines response to their extracts based on the ISO 10993-5 medical device biomaterial testing standard. In vivo mouse subcutaneous implantation (ISO 10993-6, local effects) at 2 weeks showed that the samples caused a foreign body response (FBR) with a thin fibrous encapsulation at a mean value of 28% relative skin dermis thickness; but notably, the L-KAP implant mitigated a statistically significant decrease in FBR area compared to H-KAPs (REG and/or BLH) and a lower number of cells, including immune cells of mostly macrophages and mast cells on the biomaterials surface, normalized to implant and tissue coverage. In the bulk of the capsules, blood vessels and collagen extracellular matrix densities were similar among groups. These findings suggest that small globular KAPs diffuse out of the cortex to the host-biomaterial interface which induce a slightly elevated FBR but limited to the implants surface vicinity. On-going follow-up research focuses on purer keratin-based macromolecularly organized residual hair biomaterials, those with depleted KAPs, for drug-delivery gel implants as they are deemed the most biocompatible. Statement of SignificanceHuman hair is an abundant biological product that is regularly discarded and wasted but has the potential to be a clinical implantable allograft biomaterial. There are currently just two FDA class II-510(k)-approved medical devices from hair, limited to surface / skin wound care use, and no class III-PMA or biologics-BLA implants. Also, these products and those in research and development phases are based on soluble keratin and KAPs extracts utilizing tedious processing conditions and requiring oxidation reaction for reassembly into gels and scaffolds. Here we describe that the insoluble residual hair biomaterials with organized keratin structure, higher-degree of disulfide crosslinks, and particularly those with depleted KAPs have increased biocompatibility based on pre-clinical ISO 10993 standards. This novel natural biomaterials are now being developed as drug-delivery implantable gels for clinical applications.

bioengineering↗

bioRxiv2019

NOD1 mediates non-canonical inflammasome processing of interleukin-18 in epithelial cells to Helicobacter pylori infection.

The interleukin-1 family members, IL-1{beta} and IL-18, are processed into their biologically active forms by multi-protein complexes, known as inflammasomes. Although the inflammasome pathways that mediate IL-1{beta} processing in myeloid cells have been extensively studied, those involved in IL-18 processing, particularly in non-myeloid cells, are still poorly understood. Here, we have identified the cytosolic sensor NOD1 as a key regulator of IL-18 processing in epithelial cells responding to Helicobacter pylori infection. Importantly, NOD1 processing of IL-18 occurs independently of the canonical inflammasome proteins, NLRP3 and ASC. Instead, NOD1 interacts directly with caspase-1 via homotypic binding of caspase-activation recruitment domains. We show that IL-18 is important in maintaining tissue homeostasis and protecting against pre-neoplastic changes due to gastric H. pylori infection. These findings reveal an unanticipated role for NOD1 in a new type of inflammasome that regulates epithelial cell production of bioactive IL-18 with tissue protective functions.

immunology↗