Biological Matrix Supply Chain Shortages: More Matrices Are Now Rare-the Case for Surrogate Matrices.

The COVID-19 pandemic has strained the biological matrix supply chain. An upsurge in demand driven by numerous COVID-19 therapeutic and vaccine development programs to combat the pandemic, along with logistical challenges sourcing and transporting matrix, has led to increased lead times for multiple matrices. Biological matrix shortages can potentially cause significant delays in drug development programs across the pharmaceutical and biotechnology industry.

Quartz crystal microbalance as an assay to detect anti-drug antibodies for the immunogenicity assessment of therapeutic biologics.

Because of their biological origins, therapeutic biologics can trigger an unwanted deleterious immune response with some patients. The immunogenicity of therapeutic biologics can affect drug efficacy and patient safety by the production of circulating anti-drug antibodies (ADA). In this study, quartz crystal microbalance (QCM) was developed as an assay to detect ADA.

Real-time label-free detection and kinetic analysis of Etanercept-Protein A interactions using quartz crystal microbalance.

A quartz crystal microbalance (QCM) was constructed to assess if such a biosensor has value as a complementary real-time label-free analysis platform for the biopharmaceutical industry. This was achieved through modifying QCM crystals with a low-fouling carboxymethyl-dextran layer bearing Protein A, and then injecting solutions containing Etanercept (i.e.

INS-1 cell glucose-stimulated insulin secretion is reduced by the downregulation of the 67 kDa laminin receptor.

Understanding β cell-extracellular matrix (ECM) interactions can advance our knowledge of the mechanisms that control glucose homeostasis and improve culture methods used in islet transplantation for the treatment of diabetes. Laminin is the main constituent of the basement membrane and is involved in pancreatic β cell survival and function, even enhancing glucose-stimulated insulin secretion. Most of the studies on cell responses towards laminin have focused on integrin-mediated interactions, while much less attention has been paid on non-integrin receptors, such as the 67 kDa laminin receptor (67LR).

Solution composition impacts fibronectin immobilization on carboxymethyl-dextran surfaces and INS-1 insulin secretion.

It is shown that solution composition during immobilization plays a critical role in the properties of fibronectin (FN) surfaces and their bioactivity towards insulinoma (INS-1) cell function. X-ray photoelectron spectroscopy revealed FN grafting onto low-fouling carboxymethyl-dextran (CMD) surfaces was successful with solutions composed of 10 μM CaCl(2), 10 μM MgCl(2), 10 μM MnCl(2), and 10 μM and 1mM NaCl, but unsuccessful with those made of 150 mM NaCl or 1× PBS. Circular dichroism and photon correlation spectroscopy revealed that regardless of solution composition, no measurable differences in free FN conformation prevail.

Culturing INS-1 cells on CDPGYIGSR-, RGD- and fibronectin surfaces improves insulin secretion and cell proliferation.

Rat insulinoma cells (INS-1), an immortalized pancreatic beta cell line, were cultured on low-fouling carboxymethyl-dextran (CMD) layers bearing fibronectin, the tripeptide Arg-Gly-Asp (RGD) or CDPGYIGSR, a laminin nonapeptide. INS-1 cells were non-adherent on CMD and RGE but adhered to fibronectin- and peptide-coated CMD surfaces and to tissue culture polystyrene (TCPS). On CMD bearing fibronectin and the peptides, INS-1 cells showed higher glucose-stimulated insulin secretion compared to those on TCPS, bare CMD and RGE.

In vitro morphogenesis of PANC-1 cells into islet-like aggregates using RGD-covered dextran derivative surfaces.

Substrates bearing low-fouling carboxymethyl dextran (CMD) upon which RGD is covalently grafted were validated to study PANC-1 cell differentiation in serum-free medium. When exposed to RGD-CMD, cells lightly adhered to the surface and formed islet-like aggregates (ILAs) in contact with the surface. PANC-1 were non-adherent on RGE-CMD, CMD, and tissue culture polystyrene surfaces and aggregated in suspension forming ILAs.