A Bio-Based Pro-Antimicrobial Polymer Network Via Degradable Acetal Linkages

The synthesis of a fully degradable, bio-based, sustained release, pro-antimicrobial polymer network comprised of degradable acetals (PANDA) is reported. The active antimicrobial agent – p-anisaldehyde (pA) (an extract from star anise) – was converted into a UV curable acetal containing pro-antimicrobial monomer and subsequently photopolymerized into a homogenous thiol-ene network. Under neutral to acidic conditions (pH \u3c 8), the PANDAs undergo surface erosion and exhibit sustained release of pA over 38 days. The release of pA from PANDAs was shown to be effective against both bacterial and fungal pathogens. From a combination of confocal microscopy and transmission electron microscopy, we observed that the released pA disrupts the cell membrane. Additionally, we demonstrated that PANDAs have minimal cytotoxicity towards both epithelial cells and macrophages. Although a model platform, these results point to promising pathways for the design of fully degradable sustained-release antimicrobial systems with potential applications in agriculture, pharmaceuticals, cosmetics, household/personal care, and food industries

Using Aldehyde Synergism to Direct the Design of Degradable Pro-Antimicrobial Networks

We describe the design and synthesis of degradable, dual-release, pro-antimicrobial poly(thioetheracetal) networks derived from synergistic pairs of aromatic terpene aldehydes. Initially, we identified pairs of aromatic terpene aldehydes derivatives exhibiting synergistic antimicrobial activity against Pseudomonas aeruginosa by determining fractional inhibitory concentrations. Synergistic aldehydes were converted into dialkene acetal monomers and copolymerized at various ratios with a multifunctional thiol via thiol-ene photopolymerization. The step-growth nature of the thiol-ene polymerization ensures every crosslink junction contains a degradable acetal linkage enabling a fully crosslinked polymer network to revert into its small molecule constituents upon hydrolysis, releasing the synergistic aldehydes as active antimicrobial compounds. A three-pronged approach was used to characterize the poly(thioether acetal) materials: (i) determination of the degradation/aldehyde release behavior, (ii) evaluation of the antimicrobial activity, and (iii) identification of the cellular pathways impacted by the aldehydes on a library of mutated bacteria. From this approach, a polymer network derived from a 40:60 p-bromobenzaldehyde:p-anisaldehyde monomer ratio exhibited potent antimicrobial action against Pseudomonas aeruginosa– a common opportunistic human pathogen. From a transposon mutagenesis assay, weshowed that these aldehydes target porins and multidrug efflux pumps. The aldehydes released from the poly(thioether acetal) networks exhibited negligible toxicity to mammalian tissue culture cells, supporting the potential development of these materials as dual-release antimicrobial biomaterial platforms

Pro-Antimicrobial Networks via Degradable Acetals (PANDAs) Using Thiol–Ene Photopolymerization

We describe the synthesis of pro-antimicrobial networks via degradable acetals (PANDAs) as a new paradigm for sequestration and triggered release of volatile, bioactive aldehydes. PANDAs derived from diallyl <i>p</i>-chlorobenzaldehyde acetal degrade and release <i>p</i>-chlorobenzaldehyde as an antibacterial and antifungal agent under mild conditions (pH 7.4/high humidity). We show that PANDAs enable facile access to materials with tunable release profiles, potent antimicrobial activity without triggering antimicrobial resistance, and minimal cytotoxicity

Advancing Antiracism in Community-Based Research Practices in Early Childhood and Family Mental Health

Structural racism-the ways that institutional policies, practices, and other norms operate to create and sustain race-based inequities-has historically been foundational to the operations of academic medical centers and research institutions. Since its inception, academic medicine has depended on the exploitation of vulnerable communities to achieve medical, educational, and research goals. Research practices have long ignored or taken advantage of the individuals purportedly benefiting from the research, a dynamic most manifestly true for Black, Indigenous, and People of Color (BIPOC) communities in the United States. Reflecting current practices in racial justice work, we intentionally use the term BIPOC to highlight shared experiences within racially and ethnically minoritized communities, given the history of White supremacy in the United States. We acknowledge limitations of this term, which collapses myriad unique communities and histories into one construct. Specifically, child and adolescent psychiatry has historically been driven by Eurocentric approaches, paradigms, and methodology. These nonparticipatory dominant research practices have contributed to a lack of culturally responsive interventions for BIPOC communities, a paucity of evidence-based practices with demonstrated effectiveness within BIPOC communities, and disparities in access and quality of care. Mental health research involving BIPOC communities has been replete with exploitation and inequality.