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Poly(lactic-co-glycolic) acid (PLGA) has been widely implemented in tissue engineering and drug delivery systems, stemming from its biocompatibility, controllable biodegradation, non-toxicity, non-immunogenicity, and tunable mechanical properties. PLGA exhibits a broad range of degradation times and modes, which can be finely tuned by adjusting various parameters, namely by altering the ratio of lactide and glycolide units, molecular weight, end group functionality, specimen geometry, processing temperature, and chemistry of the surrounding medium. To tailor the degradation profile, the in vitro profile should closely reflect the in vivo profile; however, the effects of mechanical loading coupled with hydrolysis on PLGA biodegradation are typically overlooked. To this end, this study investigates the combined effects of mechanical loading and hydrolysis at 37ºC on the changes in the chemical and physical properties of PLGA as it degrades with time. We found that after several days of combined loading and hydrolysis at 37ºC PLGA significantly creeps, whereas non-loaded (but hydrolyzed) specimens only slightly elongated after relatively long-term hydrolysis (~60 days). Despite this observation and perhaps counterintuitively, the hydrolyzed non-loaded samples exhibited faster degradation than hydrolyzed loaded samples. Additionally, our studies indicated the presence of bulk erosion in hydrolyzed non-loaded samples and surface erosion in hydrolyzed loaded samples. We also observed (only) physical ageing in control samples (loaded and non-loaded samples that were not immersed in PBS but exposed to 37 °C). Based on these observations, we discuss potential underlying mechanisms for the observed differences in the biodegradation behavior of PLGA specimens with and without mechanical loading. 

In proximity-driven sensing, interactions between a probe and an analyte produce a detectable signal by causing a change in distance of two probe components or signaling moieties. By interfacing such systems with DNA-based nanostructures, platforms that are highly sensitive, specific, and programmable can be designed. In this Perspective, we delineate the advantages of using DNA building blocks in proximity-driven nanosensors and provide an overview of recent progress in the field, from sensors that rapidly detect pesticides in food to probes that identify rare cancer cells in blood. We also discuss current challenges and identify key areas that need further development. 

Abstract We introduce a new class of chemical probes for activity‐based sensing of proteases, termed cleavable, locked initiator probes (CLIPs). CLIPs contain a protease‐cleavable peptide linked between two programmable DNA strands—an “initiator” DNA and a shorter “blocking” DNA. These DNA sequences are designed to hybridize, creating a “locked” hairpin‐like structure. Upon proteolytic cleavage, the initiator strand is released, triggering the activation of CRISPR‐Cas12a enzymes and producing an amplified fluorescence response. CLIPs generate more than 20‐fold turn‐on signals at room temperature (25 °C), significantly outperforming commercial probes by yielding ∼40‐fold lower limits of detection (LOD) at 100‐fold lower concentrations. Their versatility enables the detection of various disease‐relevant proteases—including the SARS‐CoV‐2 main protease, caspase‐3, matrix metalloproteinase‐7, and cathepsin B—simply by altering the peptide sequence. Importantly, CLIPs detect cathepsin B in four different colorectal cancer cell lines, highlighting their clinical potential. Taken together, the sensitivity (LOD: ∼88 pM), selectivity, and rapid assay time (down to 35 min), combined with the ability to operate in complex biological media with minimal sample preparation, position CLIPs as powerful chemical tools for activity‐based sensing of functional enzymes. 

Abstract Patterning biomolecules in synthetic hydrogels offers routes to visualize and learn how spatially‐encoded cues modulate cell behavior (e.g., proliferation, differentiation, migration, and apoptosis). However, investigating the role of multiple, spatially defined biochemical cues within a single hydrogel matrix remains challenging because of the limited number of orthogonal bioconjugation reactions available for patterning. Herein, a method to pattern multiple oligonucleotide sequences in hydrogels using thiol‐yne photochemistry is introduced. Rapid hydrogel photopatterning of hydrogels with micron resolution DNA features (≈1.5 µm) and control over DNA density are achieved over centimeter‐scale areas using mask‐free digital photolithography. Sequence‐specific DNA interactions are then used to reversibly tether biomolecules to patterned regions, demonstrating chemical control over individual patterned domains. Last, localized cell signaling is shown using patterned protein–DNA conjugates to selectively activate cells on patterned areas. Overall, this work introduces a synthetic method to achieve multiplexed micron resolution patterns of biomolecules onto hydrogel scaffolds, providing a platform to study complex spatially‐encoded cellular signaling environments.