Polyelectrolyte Microgels as Self-Defensive Biomaterials

Preventing the bacterial colonization of tissue-contacting biomedical devices is a key scientific challenge rich with potential clinical impact. Much research has concentrated on antimicrobial modification of device surfaces either by incorporating continuous elution mechanisms or by covalent surface tethering. Both strategies have shortcomings. As an alternative, we are studying a microgel-based approach to modulate the antimicrobial properties of surfaces. Notably, polyelectrolyte microgels can be electrostatically deposited to form sub-monolayer microgel coatings on complex 3-D devices. We have shown that the size and spatial distribution of antifouling PEG-based microgels critically controls the competing requirements for bacterial repulsion and tissue-cell adhesion/proliferation. Incorporating antimicrobials brings a second line of defense against bacterial colonization. To this end, we have concentrated on colloidal poly(acid) microgels such as poly(acrylic acid) (PAA) and poly(styrene sulfonate) (PSS) synthesized by suspension polymerization or membrane emulsification. After electrostatic deposition, their internal negative charge enables loading by cationic antimicrobials via a second self-assembly step driven by antimicrobial-microgel complexation. Our research concentrates on understanding and exploiting the polymer physical chemistry to identify microgel/antimicrobial combinations that can remain sequestered under physiological conditions for weeks or more, a time frame during which tissue-contacting devices are particularly prone to bacterial colonization. In addition to net electrostatic charge, aromaticity appears to play a significant role in determining the complexation strength. We have furthermore found that the sequestered antimicrobials can nevertheless be released when the loaded microgels are contacted by bacteria, a process that kills the bacteria. We speculate that this antimicrobial transfer is thermodynamically driven by the high concentration of negative charge and hydrophobicity associated with the bacterial cell envelope. Tissue cells such as osteoblasts and macrophages are, however, unable to similarly trigger release. Such bacteria-triggered release represents a new mechanism with which to create a so-called self-defensive surface - one that responds only when and where there is a bacterial challenge - with which to prevent device infection

BioScape: A Modeling and Simulation Language for Bacteria-Materials Interactions

We design BioScape, a concurrent language for the stochastic simulation of biological and bio-materials processes in a reactive environment in 3D space. BioScape is based on the Stochastic Pi-Calculus, and it is motivated by the need for individual-based, continuous motion, and continuous space simulation in modeling complex bacteria-materials interactions. Our driving example is a bio-triggered drug delivery system for infection-resistant medical implants. Our models in BioScape will help in identifying biological targets and materials strategies to treat biomaterials associated bacterial infections. The novel aspects of BioScape include syntactic primitives to declare the scope in space where species can move, diffusion rate, shape, and reaction distance, and an operational semantics that deals with the specifics of 3D locations, verifying reaction distance, and featuring random movement. We define a translation from BioScape to 3π and prove its soundness with respect to the operational semantics.Fil: Compagnoni, Adriana. Stevens Institute of Technology; Estados UnidosFil: Sharma, Vishaka. Stevens Institute of Technology; Estados UnidosFil: Bao, Yifei. Stevens Institute of Technology; Estados UnidosFil: Libera, Matthew. Stevens Institute of Technology; Estados UnidosFil: Sukhishvili, Svetlana. Stevens Institute of Technology; Estados UnidosFil: Bidinger, Philippe. VERIMAG; FranciaFil: Boglio, Livio. Universita Di Torino; ItaliaFil: Bonelli, Eduardo Augusto. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Automatic assessment of the 2-minute walk distance for remote monitoring of people with multiple sclerosis

The aim of this study was to investigate the feasibility of automatically assessing the 2-Minute Walk Distance (2MWD) for monitoring people with multiple sclerosis (pwMS). For 154 pwMS, MS-related clinical outcomes as well as the 2MWDs as evaluated by clinicians and derived from accelerometer data were collected from a total of 323 periodic clinical visits. Accelerometer data from a wearable device during 100 home-based 2MWD assessments were also acquired. The error in estimating the 2MWD was validated for walk tests performed at hospital, and then the correlation (r) between clinical outcomes and home-based 2MWD assessments was evaluated. Robust performance in estimating the 2MWD from the wearable device was obtained, yielding an error of less than 10% in about two-thirds of clinical visits. Correlation analysis showed that there is a strong association between the actual and the estimated 2MWD obtained either at hospital (r = 0.71) or at home (r = 0.58). Furthermore, the estimated 2MWD exhibits moderate-to-strong correlation with various MS-related clinical outcomes, including disability and fatigue severity scores. Automatic assessment of the 2MWD in pwMS is feasible with the usage of a consumer-friendly wearable device in clinical and non-clinical settings. Wearable devices can also enhance the assessment of MS-related clinical outcomes

Automatic Assessment of the 2-Minute Walk Distance for Remote Monitoring of People with Multiple Sclerosis

The aim of this study was to investigate the feasibility of automatically assessing the 2-Minute Walk Distance (2MWD) for monitoring people with multiple sclerosis (pwMS). For 154 pwMS, MS-related clinical outcomes as well as the 2MWDs as evaluated by clinicians and derived from accelerometer data were collected from a total of 323 periodic clinical visits. Accelerometer data from a wearable device during 100 home-based 2MWD assessments were also acquired. The error in estimating the 2MWD was validated for walk tests performed at hospital, and then the correlation (r) between clinical outcomes and home-based 2MWD assessments was evaluated. Robust performance in estimating the 2MWD from the wearable device was obtained, yielding an error of less than 10% in about two-thirds of clinical visits. Correlation analysis showed that there is a strong association between the actual and the estimated 2MWD obtained either at hospital (r = 0.71) or at home (r = 0.58). Furthermore, the estimated 2MWD exhibits moderate-to-strong correlation with various MS-related clinical outcomes, including disability and fatigue severity scores. Automatic assessment of the 2MWD in pwMS is feasible with the usage of a consumer-friendly wearable device in clinical and non-clinical settings. Wearable devices can also enhance the assessment of MS-related clinical outcomes

The 2023 Orthopedic Research Society's international consensus meeting on musculoskeletal infection: Summary from the in vitro section

Antimicrobial strategies for musculoskeletal infections are typically first developed with in vitro models. The In Vitro Section of the 2023 Orthopedic Research Society Musculoskeletal Infection international consensus meeting (ICM) probed our state of knowledge of in vitro systems with respect to bacteria and biofilm phenotype, standards, in vitro activity, and the ability to predict in vivo efficacy. A subset of ICM delegates performed systematic reviews on 15 questions and made recommendations and assessment of the level of evidence that were then voted on by 72 ICM delegates. Here, we report recommendations and rationale from the reviews and the results of the internet vote. Only two questions received a ≥90% consensus vote, emphasizing the disparate approaches and lack of established consensus for in vitro modeling and interpretation of results. Comments on knowledge gaps and the need for further research on these critical MSKI questions are included