Biology subjects

Vishwanath, K.

Publications and source records attributed to Vishwanath, K..

4 recordsLinked to original sources

bioRxiv2025

Delayed lubricin injection improves cartilage repair tissue quality in an in vivo rabbit osteochondral defect model

Osteochondral lesions (OCL) are common among young patients and often require surgical interventions since cartilage has a poor capacity for self-repair. Bone marrow stimulation (BMS) has been used clinically for decades to treat OCLs, however a persisting challenge with BMS and other cartilage repair strategies is the inferior quality of the resulting fibrocartilaginous repair tissue. Lubrication-based therapies have the potential to improve the quality of cartilage repair tissue as joint lubrication is linked to local cartilage tissue strains and subsequent cellular responses including death and apoptosis. Recently, a full length recombinant human lubricin (rhLubricin) was developed and has been shown to lower friction in cartilage. This study investigated the effect of a single delayed injection of rhLubricin on cartilage repair in an in vivo rabbit OCL model using gross macroscopic evaluation, surface profilometry, histology, and tribology. Moderate improvement in macroscopic scores for cartilage repair were observed. Notably, quantitative analysis of Safranin-O histology showed that rhLubricin treated joints had significantly higher glycosaminoglycan content compared to saline treated joints, and there were no differences in repair integration between groups. Furthermore, rhLubricin treated joints had significantly lower friction coefficients tested across three sliding speeds compared to saline treated joints (rhLubricin: 0.15 {+/-} 0.03 at 0.1 mm/s to 0.12 {+/-} 0.03 at 10 mm/s, Saline: 0.22 {+/-} 0.06 at 0.1 mm/s to 0.19 {+/-} 0.05 at 10 mm/s). Overall, a single delayed injection of rhLubricin improved the quality and lubricating ability of the repair cartilage tissue without inhibiting repair tissue integration.

bioengineering↗

bioRxiv2025

Modeling tumor dynamics and predicting response to chemo-, targeted-, and immune-therapies in a murine model of pancreatic cancer

We seek to establish a parsimonious mathematical framework for understanding the interaction and dynamics of the response of pancreatic cancer to the NGC triple chemotherapy regimen (mNab-paclitaxel, gemcitabine, and cisplatin), stromal-targeting drugs (calcipotriol and losartan), and an immune checkpoint inhibitor (anti-PD-L1). We developed a set of ordinary differential equations describing changes in tumor size (growth and regression) under the influence of five cocktails of treatments. Model calibration relies on three tumor volume measurements obtained over a 14-day period in a genetically engineered pancreatic cancer model (KrasLSLG12D-Trp53LSLR172H-Pdx1-Cre). Our model reproduces tumor growth in the control and treatment scenarios with an average concordance correlation coefficient (CCC) of 0.99{+/-}0.01. We conduct leave-one-out predictions (average CCC=0.74{+/-}0.06), mouse-specific predictions (average CCC=0.75{+/-}0.02), and hybrid, group-informed, mouse-specific predictions (average CCC=0.85{+/-}0.04). The developed mathematical model demonstrates high accuracy in fitting the experimental tumor data and a robust ability to predict tumor response to treatment. This approach has important implications for optimizing combination NGC treatment strategies.

bioinformatics↗

bioRxiv2024

Recombinant manufacturing of multispecies biolubricants

Lubricin, a lubricating glycoprotein abundant in synovial fluid, forms a low-friction brush polymer interface in tissues exposed to sliding motion including joints, tendon sheaths, and the surface of the eye. Despite its therapeutic potential in diseases such as osteoarthritis and dry eye disease, there are few sources available. Through rational design, we developed a series of recombinant lubricin analogs that utilize the species-specific tissue-binding domains at the N- and C-termini to increase biocompatibility while replacing the central mucin domain with an engineered variant that retains the lubricating properties of native lubricin. In this study, we demonstrate the tissue binding capacity of our engineered lubricin product and its retention in the joint space of rats. Next, we present a new bioprocess chain that utilizes a human-derived cell line to produce O-glycosylation consistent with that of native lubricin and a purification strategy that capitalizes on the positively charged, hydrophobic N- and C-terminal domains. The bioprocess chain is demonstrated at 10 L scale in industry-standard equipment utilizing commonly available ion exchange, hydrophobic interaction and size exclusion chromatography resins. Finally, we confirmed the purity and lubricating properties of the recombinant biolubricant. The biomolecular engineering and bioprocessing strategies presented here are an effective means of lubricin production and could have broad applications to the study of mucins in general.

bioengineering↗

bioRxiv2022

Light diffusion in layered media: A numerical study in the spatial and time-domains

Accurate and efficient forward models of photon migration in heterogeneous geometries are important for many applications of light in medicine because many biological tissues exhibit a layered structure, with each layer having independent optical properties and thickness. Unfortunately, closed form analytical solutions are not readily available for layered tissue-models, and often are modeled using computationally expensive numerical techniques or theoretical approximations that limit accuracy and real-time analysis. Here, we develop an open-source accurate, efficient, and stable numerical routine to solve the diffusion equation in the steady-state and time-domain for a layered cylinder tissue model with an arbitrary number of layers and specified thickness and optical coefficients. We show that the steady-state (< 0.1 ms) and time-domain (< 0.5 ms) fluence (for an 8-layer medium) can be calculated with absolute numerical errors approaching machine precision. The numerical implementation increased computation speed by 3 to 4 orders of magnitude compared to previously reported theoretical solutions in layered media. We verify our solutions asymptotically to homogeneous tissue geometries using closed form analytical solutions to assess convergence and numerical accuracy. Approximate solutions to compute the reflected intensity are presented which can decrease the computation time by an additional 2-3 orders of magnitude. We also compare our solutions for 2, 3, and 5 layered media to gold-standard Monte Carlo simulations in layered tissue models of high interest in biomedical optics (e.g. skin/fat/muscle and brain). The presented routine could enable more robust real-time data analysis tools in heterogeneous tissues that are important in many clinical applications such as functional brain imaging and diffuse optical spectroscopy.

bioengineering↗