Microrheology analyzes the microscopic behavior of complex materials by measuring the diffusion and transport of embedded particle probes. This experimental method can provide valuable insight into the design of biomaterials with the ability to connect material properties and biological responses to polymer-scale dynamics and interactions. In this review, we discuss how microrheology can be harnessed as a characterization method complementary to standard techniques in biomaterial design. We begin by introducing the core principles and instruments used to perform microrheology. We then review previous studies that incorporate microrheology in their design process and highlight biomedical applications that have been supported by this approach. Overall, this review provides rationale and practical guidance for the utilization of microrheological analysis to engineer novel biomaterials.
Despite the promise of antimicrobial peptides (AMPs) as treatments for antibiotic‐resistant infections, their therapeutic efficacy is limited due to the rapid degradation and low bioavailability of AMPs. To address this, we have developed and characterized a synthetic mucus (SM) biomaterial capable of delivering LL37 AMPs and enhancing their therapeutic effect. LL37 is an AMP that exhibits a wide range of antimicrobial activity against bacteria, including Pseudomonas aeruginosa. LL37 loaded SM hydrogels demonstrated controlled release with 70%–95% of loaded LL37 over 8 h due to charge‐mediated interactions between mucins and LL37 AMPs. Compared to treatment with LL37 alone where antimicrobial activity was reduced after 3 h, LL37‐SM hydrogels inhibited P. aeruginosa (PAO1) growth over 12 h. LL37‐SM hydrogel treatment reduced PAO1 viability over 6 h whereas a rebound in bacterial growth was observed when treated with LL37 only. These data demonstrate LL37‐SM hydrogels enhance antimicrobial activity by preserving LL37 AMP activity and bioavailability. Overall, this work establishes SM biomaterials as a platform for enhanced AMP delivery for antimicrobial applications.
Despite the promise of antimicrobial peptides (AMPs) as treatments for antibiotic-resistant infections, their therapeutic efficacy is limited due to the rapid degradation and low bioavailability of AMPs. To address this, we have developed and characterized a synthetic mucus (SM) biomaterial capable of delivering AMPs and enhancing their therapeutic effect. LL37 loaded SM hydrogels demonstrated controlled release of LL37 over 8 hours as a result of charge-mediated interactions between mucins and LL37 AMPs. Compared to treatment with LL37 alone where antimicrobial activity was reduced after 3 hours, LL37-SM hydrogels inhibited Pseudomonas aeruginosa PAO1 growth over 12 hours. LL37-SM hydrogel treatment reduced PAO1 viability over 6 hours whereas a rebound in bacterial growth was observed when treated with LL37 only. These data demonstrate LL37-SM hydrogels enhance antimicrobial activity by preserving LL37 AMP activity and bioavailability. Overall, this work establishes SM biomaterials as a platform for enhanced AMP delivery for antimicrobial applications.
Mucosal tissues are often a desirable site of drug action to treat disease and engage the immune system. However, systemically administered drugs suffer from limited bioavailability in mucosal tissues where technologies to enable direct, local delivery to these sites would prove useful. In this Spotlight on Applications article, we discuss hydrogels as an attractive means for local delivery of therapeutics to address a range of conditions affecting the eye, nose, oral cavity, gastrointestinal, urinary bladder, and vaginal tracts. Considering the barriers to effective mucosal delivery, we provide an overview of the key parameters in the use of hydrogels for these applications. Finally, we highlight recent work demonstrating their use for inflammatory and infectious diseases affecting these tissues.
Cystic fibrosis (CF) is a muco-obstructive lung disease where inflammatory responses due to chronic infection result in the accumulation of neutrophil extracellular traps (NETs) in the airways. NETs are web-like complexes comprised mainly of decondensed chromatin that function to capture and kill bacteria. Prior studies have established excess release of NETs in CF airways increases viscoelasticity of mucus secretions and reduces mucociliary clearance. Despite the pivotal role of NETs in CF disease pathogenesis, current in vitro models of this disease do not account for their contribution. Motivated by this, we developed a new approach to study the pathobiological effects of NETs in CF by combining synthetic NET-like biomaterials, composed of DNA and histones, with an in vitro human airway epithelial cell culture model. To determine the impact of synthetic NETs on airway clearance function, we incorporated synthetic NETs into mucin hydrogels and cell culture derived airway mucus to assess their rheological and transport properties. We found that the addition of synthetic NETs significantly increases mucin hydrogel and native mucus viscoelasticity. As a result, mucociliary transport in vitro was significantly reduced with the addition of mucus containing synthetic NETs. Given the prevalence of bacterial infection in the CF lung, we also evaluated the growth of Pseudomonas aeruginosa in mucus with or without synthetic NETs. We found mucus containing synthetic NETs promoted microcolony growth and prolonged bacterial survival. Together, this work establishes a new biomaterial enabled approach to study innate immunity mediated airway dysfunction in CF.
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