Biology subjects

Wood, S. T.

Publications and source records attributed to Wood, S. T..

4 recordsLinked to original sources

bioRxiv2026

Microfluidic Osteoarthritis-on-a-Chip for Evaluating Joint-Cell Responses to Tanezumab, a Humanized Anti-NGF Monoclonal Antibody

Osteoarthritis (OA) drug development remains constrained by preclinical models that fail to recapitulate the multicellular interactions that regulate human joint inflammation and extracellular matrix degeneration in response to investigational drugs. Tanezumab, a humanized anti-nerve growth factor monoclonal antibody developed for non-opioid pain relief, advanced to late-stage clinical trials but was discontinued due to unresolved joint-localized safety concerns, including rapidly progressive OA. This study evaluated whether a human microfluidic joint-on-a-chip co-culture system could detect early biomarker responses to tanezumab exposure that were not apparent in conventional chondrocyte monoculture. Tanezumab was first tested in human chondrocyte monoculture under untreated and disease-like (i.e., IL-1{beta}-treated) conditions. Across a 20-analyte panel of inflammatory and matrix-remodeling biomarkers, statistically significant monoculture responses to tanezumab were limited to decreased IL-1{beta} from 335 to 132 pg/mL ([~]0.39-fold) and increased IL-8 from 575 to 675 pg/mL ([~]1.17-fold). Major OA-associated matrix-remodeling markers, including MMP-1, MMP-3, and MMP-13, remained largely unchanged, indicating that monoculture conditions are insufficiently sensitive to detect clinically predictive drug-related molecular changes. Tanezumab was then evaluated in co-cultures containing chondrocytes, osteoblasts, fibroblast-like cells, and macrophages under low-inflammation (i.e., M0 macrophage-based) and high-inflammation (i.e., M1 macrophage-based) conditions. In the M0-based co-culture, tanezumab increased MMP-1 from [~]4.20 x 104 to [~]6.20 x 104 pg/mL ([~]1.48-fold), MMP-3 from [~]8.00 x 104 to [~]1.20 x 105 pg/mL ([~]1.50-fold), and MCP-1 from 2.85 x 103 to 4.31 x 103 pg/mL ([~]1.51-fold). In contrast, the M1-based co-culture showed decreases in MMP-13 from [~]1.66 x 104 to [~]1.17 x 104 pg/mL ([~]0.70-fold) and IFN-{gamma} from [~]1.95 x 104 to [~]1.56 x 104 pg/mL ([~]0.80-fold), changes that may appear beneficial despite the drugs known clinical risks. Collectively, these findings show that low-inflammation multicellular co-culture revealed coordinated matrix remodeling and inflammatory responses to NGF blockade that were missed in monoculture and were partly obscured in highly stimulated disease-like conditions. This platform may provide a useful, human-relevant approach for safety signal assessment and early evaluation of OA therapeutics within a defined context of use focused on joint-specific, tissue-level drug-response testing.

bioengineering↗

bioRxiv2026

Microfluidic Osteoarthritis-on-a-Chip: Modeling Human Joint Inflammation

Osteoarthritis (OA) is a multifactorial joint disease driven by complex interactions among chondrocytes, osteoblasts, fibroblasts, and immune cells across cartilage, bone, and synovial tissues. Conventional monoculture systems are unable to capture this crosstalk, limiting their physiological relevance. Building on our previously established joint-on-a-chip platform, this study evaluated multicellular communication and assessed whether a microfluidic co-culture provides a more realistic representation of joint inflammation compared with monoculture models. Two configurations were established: a healthy, low-inflammation model containing M0 macrophages and an OA-like, high-inflammation model with M1 macrophages. In healthy models, co-culture significantly increased MMP-1 ([~]4-fold), MMP-3 ([~]15-fold), TIMP-2 ([~]5-fold), IL-6 ([~]6-fold), and IL-8 ([~]5-fold) relative to monoculture, indicating that endogenous signaling initiates basal matrix remodeling and inflammatory pathways. In disease models, M1-driven co-culture elevated MMP-10 ([~]300-fold) and MMP-13 ([~]60-fold), along with TIMP-2 ([~]5-fold), compared with monoculture, reflecting amplified catabolic activation. Direct comparison of disease versus healthy co-culture revealed additional increases in MMP-10 ([~]55-fold), MMP-13 ([~]95-fold), MCP-1 ([~]1.6-fold), MMP-1 ([~]1.6-fold), MMP-3 ([~]1.8-fold), TIMP-1 ([~]1.4-fold), and TIMP-2 ([~]1.5-fold), representing a macrophage-mediated shift from homeostasis to OA-like pathology. However, neither IL-1 nor TNF, each a key inflammatory mediator of OA, differed measurably between healthy and disease models under either monoculture or co-culture conditions. Thus, the microfluidic joint inflammation-on-a-chip model presented here more faithfully recapitulates the pathogenic MMP profile of OA than monoculture systems, but it does not yet fully recapitulate the pathogenic inflammatory environment of OA.

cell biology↗

bioRxiv2025

Microfluidic Co-Culture for Modeling Human Joint Inflammation in Osteoarthritis Research

Here we present a microfluidic model that allows for co-culture of human osteoblasts, chondrocytes, fibroblasts, and macrophages of both quiescent (M0) and pro-inflammatory (M1) phenotypes, maintaining initial viability of each cell type at 24 h of co-culture. We established healthy (M0-based) and diseased (M1-based) joint models within this system. An established disease model based on supplementation of IFN-{gamma} and LPS in cell culture media was used to induce an M1 phenotype in macrophages to recapitulate inflammatory conditions found in OA. Cell viability was assessed using NucBlue Live and NucGreen Dead fluorescent stains, with mean viability of 83.9% {+/-} 14% and 83.3% {+/-} 12% for healthy and diseased models, respectively, compared with 93.3% {+/-} 4% for cell in standard monoculture conditions. Cytotoxicity was assessed via a lactate dehydrogenase (LDH) assay and showed no measurable increase in LDH release into the culture medium under co-culture conditions, indicating that neither model promotes a loss of cell membrane integrity due to cytotoxic effects. Cellular metabolic activity was assessed using a PrestoBlue assay and indicated increased cellular metabolic activity in co-culture, with levels 5.9 {+/-} 3.2 times mean monolayer cell metabolic activity levels in the healthy joint model and 5.3 {+/-} 3.4 times mean monolayer levels in the diseased model. Overall, these findings indicate that the multi-tissue nature of in vivo human joint conditions can be recapitulated by our microfluidic co-culture system at 24 h and thus this model serves as a promising tool for studying the pathophysiology of rheumatic diseases and testing potential therapeutics.

bioengineering↗

bioRxiv2019

CellWell: A micropatterned biphasic nanocomposite platform for culturing chondrocytes

Graphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC=\"FIGDIR/small/790030v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (25K):\norg.highwire.dtl.DTLVardef@e0a6c0org.highwire.dtl.DTLVardef@e3b9f7org.highwire.dtl.DTLVardef@c60cb6org.highwire.dtl.DTLVardef@6cb884_HPS_FORMAT_FIGEXP M_FIG C_FIG AbstractWe present a unique micropatterned nanocomposite cell culture platform to model articular cartilage that is suitable for high-throughput single-cell analyses using standard imaging techniques. This platform, the CellWell, is constructed out of a thin, optically transparent substrate that is lithographically micropatterned with a network of wells sized to fit individual cells. The substrate material consists of a thin layer of agarose hydrogel embedded with polyvinyl alcohol nanofibers. The geometries of the wells are designed to reinforce a physiological morphology, thereby combining the physiological advantages of 3D culture systems with the practical advantages of 2D systems. CellWells were found to have compressive moduli of 144 {+/-} 11.5 kPa and 158 {+/-} 0.6 kPa at strain rates of 5 m/s and 15 m/s. The compressive moduli were determined at two different strain rates to allow for comparison of CellWell stiffness with published values of pericellular matrix and with observed values of articular cartilage, which could not be indented at the same rate. Articular chondrocytes seeded in a CellWell were found to maintain their spheroidal morphology more effectively than those seeded in monolayer cultures and to be more easily imaged than those seeded in a 3D scaffold of identical thickness. Through its ease of use and ability to maintain the physiological morphology of chondrocytes, we expect that the CellWell will enhance the clinical translatability of future studies conducted using this culture platform.

bioengineering↗