Biology subjects

Rios, J. L.

Publications and source records attributed to Rios, J. L..

3 recordsLinked to original sources

bioRxiv2026

Chiral Histidine-Modified Gold Nanoclusters Loaded into Cationic Lipid Nanoparticles for Treatment of Biofilm-associated Infections

Antimicrobial resistance has heightened the risk of device-associated infections, in which Staphylococcus aureus (S. aureus) biofilms persist through extracellular-matrix protection and marked physiological heterogeneity. Gold nanoclusters (AuNCs) can disrupt biofilms via redox-associated stress, but limited in vivo stability and poor local retention constrain their translational potential. Here, we synthesized chiral histidine-modified AuNCs (D-, L-, and DL-AuNCs) and formulated them into mildly cationic lipid nanoparticles (AuNCs@LNP) by microfluidic assembly to enhance biofilm engagement while preserving nanocluster identity. The resulting particles were [~]100-120 nm with high gold loading and a modest charge reversal. In established S. aureus USA300 biofilms, free DL-AuNCs reduced viable burden by up to 5.6 log10 CFU/mL, suppressed metabolic activity, and increased ROS signaling. Notably, LNP encapsulation maintained bactericidal activity and further improved killing by [~]1 log10 CFU at matched Au dose, while substantially enhancing biomass removal (crystal violet residual biomass: 63.77% vs 45.17%), consistent with carrier-mediated matrix destabilization. In a subcutaneous implant infection model, a single perilesional dose of DL-AuNCs@LNP reduced implant-associated bacterial burden by 2.6 log10 CFU per implant versus PBS. These results establish a modular antibiofilm platform that couples nanocluster-driven killing with lipid-facilitated biofilm disruption and defines an efficacy-tolerability window to guide optimization of locally delivered antibiofilm nanomedicines. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=61 SRC="FIGDIR/small/707929v2_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@119134forg.highwire.dtl.DTLVardef@142e7b2org.highwire.dtl.DTLVardef@1799550org.highwire.dtl.DTLVardef@139c33a_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2025

Refining the Bio-manufacturing of Microalgae-derived Extracellular Vesicles as a Potential Nanotherapeutic for Osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease marked by oxidative stress, chronic inflammation, and cartilage degradation. Current treatments are limited and fail to address the underlying disease mechanisms. Extracellular vesicles (EVs) have emerged as promising nanotherapeutics; however, mammalian-derived EVs face cost and scalability challenges. Microalgae represent a sustainable alternative, yet their potential as EV biofactories for regenerative medicine remains unknown. This study aims to refine the bio-manufacturing of microalgae EVs as a next-generation nanotherapeutic for OA. Microalgae species (Chlorella sorokiniana, Synechococcus sp., Leptolyngbya sp., Chlamydomonas reinhardtii CC1690) were screened under varying photoperiods (0h, 16h, 24h light/day) to assess the influence on viability, growth and EV production. EVs were characterized by transmission electron microscopy, nanoparticle tracking analysis, protein quantification and immunoblotting. Their antioxidant capacity, cellular recruitment, and therapeutic efficacy were evaluated in a cytokine-induced OA-like in vitro model. Our findings demonstrated that microalgae growth and EV yield were highly light-dependent, with all species maintaining high viability (>80%) across different photoperiods. Notably, Leptolyngbya sp. (Leptolyngbya) exhibited the fastest growth and highest EV yield under extended illumination, producing EVs with strong antioxidant activity. Leptolyngbya-derived EVs (Lepto-EVs) enhanced the proliferation and migration of human bone marrow-derived mesenchymal stromal cells and provided protection against matrix degradation within a cytokine-induced OA-like model. These findings position microalgae, particularly Leptolyngbya, as a highly scalable and sustainable producer of therapeutic EVs. Lepto-EVs offer a potent, cell-free nanotherapeutic exhibiting anti-catabolic properties alleviating cytokine-induced matrix degradation in an OA-like milieu, establishing microalgae EVs as a promising, cost-effective frontier in regenerative nanomedicine. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=98 SRC="FIGDIR/small/685512v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@ac6400org.highwire.dtl.DTLVardef@1d948a7org.highwire.dtl.DTLVardef@30fc13org.highwire.dtl.DTLVardef@1f576c8_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2021

A musculoskeletal finite element model of rat knee joint for evaluating cartilage biomechanics during gait

Abnormal loading of the knee due to injuries or obesity is thought to contribute to the development of osteoarthritis (OA). Small animal models have been used for studying OA progression mechanisms. However, numerical models to study cartilage responses under dynamic loading in preclinical animal models have not been developed. Here we present a musculoskeletal finite element (FE) model of a rat knee joint to evaluate cartilage biomechanical responses during a gait cycle. The rat knee joint geometries were obtained from a 3-D MRI dataset and the boundary conditions regarding loading in the joint were extracted from a musculoskeletal model of the rat hindlimb. The fibril-reinforced poroelastic (FRPE) properties of the rat cartilage were derived from data of mechanical indentation tests. Our numerical results showed the relevance of simulating anatomical and locomotion characteristics in the rat knee joint for estimating tissue responses such as contact pressures, stresses, strains, and fluid pressures. We found that the contact pressure and maximum principal strain were virtually constant in the medial compartment whereas they showed the highest values at the beginning of the gait cycle in the lateral compartment. Furthermore, we found that the maximum principal stress increased during the stance phase of gait, with the greatest values at midstance. We anticipate that our approach serves as a first step towards investigating the effects of gait abnormalities on the adaptation and degeneration of rat knee joint tissues and could be used to evaluate biomechanically-driven mechanisms of the progression of OA as a consequence of joint injury or obesity. Author SummaryOsteoarthritis is a disease of the musculoskeletal system which is characterized by the degradation of articular cartilage. Changes in the knee loading after injuries or obesity contribute to the development of cartilage degeneration. Since injured cartilage cannot be reversed back to intact conditions, small animal models have been widely used for investigating osteoarthritis progression mechanisms. Moreover, experimental studies have been complemented with numerical models to overcome inherent limitations such as cost, difficulties to obtain accurate measures and replicate degenerative situations in the knee joint. However, computational models to study articular cartilage responses under dynamic loading in small animal models have not been developed. Thus, here we present a musculoskeletal finite element model of a rat knee joint to evaluate cartilage biomechanical responses during gait. Our computational model considers both the anatomical and locomotion characteristics of the rat knee joint for estimating mechanical responses in the articular cartilage. We suggest that our approach can be used to investigate tissue adaptations based on the mechanobiological responses of the cartilage to prevent the progression of osteoarthritis.

bioengineering↗