Neutrophils are essential effector cells for mediating rapid host defense and their insufficiency arising from therapy‐induced side‐effects, termed neutropenia, can lead to immunodeficiency‐associated complications. In autologous hematopoietic stem cell transplantation (HSCT), neutropenia is a complication that limits therapeutic efficacy. Here, we report the development and in vivo evaluation of an injectable, biodegradable hyaluronic acid (HA)‐based scaffold, termed HA cryogel, with myeloid responsive degradation behavior. In mouse models of immune deficiency, we show that the infiltration of functional myeloid‐lineage cells, specifically neutrophils, is essential to mediate HA cryogel degradation. Post‐HSCT neutropenia in recipient mice delayed degradation of HA cryogels by up to 3 weeks. We harnessed the neutrophil‐responsive degradation to sustain the release of granulocyte colony stimulating factor (G‐CSF) from HA cryogels. Sustained release of G‐CSF from HA cryogels enhanced post‐HSCT neutrophil recovery, comparable to pegylated G‐CSF, which, in turn, accelerated cryogel degradation. HA cryogels are a potential approach for enhancing neutrophils and concurrently assessing immune recovery in neutropenic hosts.

Skin consists of a lamellar structure with diverse cell types (e.g., immune cells, melanocytes, and basal cells) that periodically detach from the basement membrane, move to the surface, and die for self-renewal. [3] Melanocytes are a critical cell type that generate melanin to absorb UV light (290-400 nm), which is a major risk for skin diseases (e.g., melanoma) due to DNA damage. [4][5][6][7] Here, melanin-containing organelles called melanosomes are transferred to the surrounding keratinocytes. This increase in melanosome concentration leads to darker skin phototypes, and darker phototypes can be a function of racial background or previous sun exposure, that is, tanning. [8] Indeed, skin pigmentation depends on variations in the size, number, clustering phase, and the proportions between melanin species (e.g., eumelanin and pheomelanin). [9] Skin pigmentation has been quantified using melanosome volume fraction (M f ) parameter: 1.3-6.3% for lightly pigmented adults, 11-16% for moderately pigmented adults, and 18-43% for darkly pigmented adults. [10] Variations in skin phototypes can complicate biomedical optics. Melanin absorption increases linearly from 800 to 600 nm and exponentially from 600 to 300 nm. [11,12] Darker skin phototypes can absorb and scatter more photons: as a result, incident light is attenuated before it reaches the target of interest, and signal transmission can be impeded back to the sensor. Therefore, variations in skin phototypes have negatively affected many forms of medical optic technology including pulse oximetry, [13,14] cerebral tissue oximeters, [15] optical coherence tomography, [16] wearable electronics, [17][18][19] photoacoustic (PA) imaging, [20] fluorescence imaging, [21] and photothermal therapy. [22] One recent study compared 48 097 pairs of oxygen saturation levels measured by pulse oximetry and arterial blood gas test obtained from 8675 white patients and 1326 black patients. [13] The results found that pulse oximetry had trouble in diagnosing hypoxemia in 11% Black patients and 3% white patients due to light absorption by melanin. [13,14] Furthermore, wearable electronics (e.g., smartwatches) have reported inaccuracies in heart rate readings occurring more often in users with dark skin than light skin. [17,18] Clearly, the impact of differences in skin phototypes underscore the ongoing need to understand and correct racial bias in optical technologies. While larger 3D-bioprinted skin-mimicking phantoms with skin colors ranging across the Fitzpatrick scale are reported. These tools can help understand the impact of skin phototypes on biomedical optics. Synthetic melanin nanoparticles of different sizes (70-500 nm) and clusters are fabricated to mimic the optical behavior of melanosome. The absorption coefficient and reduced scattering coefficient of the phantoms are comparable to real human skin. Further the melanin content and distribution in the phantoms versus real human skins are validated via photoacoustic (PA) imaging. The PA signal of the phantom can be improved ...

Disease modifying antirheumatic drugs (DMARDs) have improved the prognosis of autoimmune inflammatory arthritides but a large fraction of patients display partial or nonresponsiveness to front-line DMARDs. Here, an immunoregulatory approach based on sustained joint-localized release of all-trans retinoic acid (ATRA), which modulates local immune activation and enhances disease-protective T cells and leads to systemic disease control is reported. ATRA imprints a unique chromatin landscape in T cells, which is associated with an enhancement in the differentiation of naïve T cells into anti-inflammatory regulatory T cells (T reg ) and suppression of T reg destabilization. Sustained release poly-(lactic-co-glycolic) acid (PLGA)-based biodegradable microparticles encapsulating ATRA (PLGA-ATRA MP) are retained in arthritic mouse joints after intra-articular (IA) injection. IA PLGA-ATRA MP enhance migratory T reg which in turn reduce inflammation and modify disease in injected and uninjected joints, a phenotype that is also reproduced by IA injection of T reg . PLGA-ATRA MP reduce proteoglycan loss and bone erosions in the SKG and collagen-induced arthritis mouse models of autoimmune arthritis. Strikingly, systemic disease modulation by PLGA-ATRA MP is not associated with generalized immune suppression. PLGA-ATRA MP have the potential to be developed as a disease modifying agent for autoimmune arthritis.

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Lipids constitute a diverse class of molecular regulators with ubiquitous physiological roles in sustaining life. These carbon‐rich compounds are primarily sourced from exogenous sources and may be used directly as structural cellular building blocks or as a substrate for generating signaling mediators to regulate cell behavior. In both of these roles, lipids play a key role in both immune activation and suppression, leading to inflammation and resolution, respectively. The simple yet elegant structural properties of lipids encompassing size, hydrophobicity, and molecular weight enable unique biodistribution profiles that facilitate preferential accumulation in target tissues to modulate relevant immune cell subsets. Thus, the structural and functional properties of lipids can be leveraged to generate new materials as pharmacological agents for potently modulating the immune system. Here, we discuss the properties of three classes of lipids: polyunsaturated fatty acids, short‐chain fatty acids, and lipid adjuvants. We describe their immunoregulatory functions in modulating disease pathogenesis in preclinical models and in human clinical trials. We conclude with an outlook on harnessing the diverse and potent immune modulating properties of lipids for immunoregulation.

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