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Tumor-associated adipocytes (TAAs) recruit monocytes and promote their differentiation into tumor-associated macrophages (TAMs) that support tumor development. Here, TAAs are engineered to promote the polarization of TAMs to the tumor suppressive M1 phenotype. Telratolimod, a toll-like receptor 7/8 agonist, is loaded into the lipid droplets of adipocytes to be released at the tumor site upon tumor cell-triggered lipolysis. Locally administered drug-loaded adipocytes increased tumor suppressive M1 macrophages in both primary and distant tumors and suppressed tumor growth in a melanoma model. Furthermore, drug-loaded adipocytes improved CD8+ T cell-mediated immune responses within the tumor microenvironment and favored dendritic cell maturation in the tumor draining lymph nodes.

A microdevice that offers glucagon supplements in a safe, non-invasive, and glucose-responsive manner is ideal for avoiding fatal hypoglycemia consequences from insulin overdosage during daily diabetes treatment. However, mold-assisted microfabrication of biomedical materials or devices typically needs high-resolution laser ablation to scale down structural design. In addition, the majority of the polymeric drug delivery materials being used to fabricate devices are dissolvable or deformable in aqueous environments, which restricts washing-based cleaning and purification procedures post shape fixation. This study leverages the design flexibility of 3D printing-assisted mold casting and presents a shrinking microfabrication approach that allows subsequent washing procedures to remove toxic monomer residues during polymerization. The feasibility of this approach is demonstrated by developing a glucose-responsive transdermal glucagon microneedle patch through matrix volume change-mediated release kinetic control. Shown in the type 1 diabetic mouse model, this transdermal patch can reverse the occurrence of hypoglycemia while lowering the risk of monomer residue-induced irritation during treatment. Freeing from the restrain of molding resolution for microstructure design, this shrinking methodology further provides an insight into post-fabrication purifications of biomedical materials.

Periodontitis is initiated by dysbiosis of the oral microbiome. Pathogenic bacteria elicit ineffective immune responses, which damage surrounding tissues and lead to chronic inflammation. Although current treatments typically aim for microbial eradication, they fail to address the significance of immune cell reactions in disease progression. Here, we searched for small molecules as drug candidates and identified a bifunctional antibiotic, azithromycin (AZM), that not only inhibits bacterial growth but also modulates immune cells to suppress inflammation. We further engineered a dissolvable microneedle patch loaded with biodegradable microparticles for local and painless delivery of AZM to the gingival tissues. Inflammatory cytokines were decreased while anti-inflammatory cytokines and M2 macrophage were increased with AZM treatments in vitro. In vivo delivery of the AZM-loaded microneedle patch demonstrated the same effects on cytokine secretion and the promotion of tissue healing and bone regeneration. In addition, microparticles containing anti-inflammatory interleukin-4 alone or in combination with separately-formulated AZM microparticles, had similar or slightly enhanced therapeutic outcomes respectively. The bimodal action of AZM obviates the necessity for separate antibacterial and immunomodulatory agents, providing a practical and streamlined approach for clinical treatment. Our findings also demonstrate the therapeutic efficacy of microparticles delivery into the soft tissues by a minimally invasive and fast-degrading microneedle patch and offer a novel therapeutic approach for the treatment of periodontitis and other diseases through immunomodulation. Highlights: • Dual actions of a single compound with both antibiotic and immunomodulatory effects can suppress inflammation and promote tissue regeneration. • Fast-dissolving microneedle patch enables minimally invasive and local delivery of biodegradable microparticles as distributive depots for sustained release of therapeutics in diseased tissues. [ABSTRACT FROM AUTHOR]

Abstract: Advanced optical fibers and photonic structures play important roles in neuroscience research, along with recent progresses of genetically encoded optical actuators and indicators. Most techniques for optical neural implants rely on fused silica or long‐lasting polymeric fiber structures. In this paper, implantable and biodegradable optical fibers based on poly( l‐lactic acid) (PLLA) are presented. PLLA fibers with dimensions similar to standard silica fibers are constructed using a simple thermal drawing process at around 220 °C. The formed PLLA fibers exhibit high mechanical flexibility and optical transparency, and their structural evolution and optical property changes are systematically studied during in vitro degradation. In addition, their biocompatibility with brain tissues is evaluated in living mice, and full in vivo degradation is demonstrated. Finally, PLLA fibers are implemented as a tool for intracranial light delivery and detection, realizing deep brain fluorescence sensing and optogenetic interrogation in vivo. The presented materials and device platform offer paths to fully biocompatible and bioresorbable photonic systems for biomedical uses. [ABSTRACT FROM AUTHOR]