Modulating Lipid-Polymer Nanoparticles' Physicochemical Properties to Alter Macrophage Uptake.

Macrophage uptake of nanoparticles is highly dependent on the physicochemical characteristics of those nanoparticles. Here, we have created a collection of lipid-polymer nanoparticles (LPNPs) varying in size, stiffness, and lipid makeup to determine the effects of these factors on uptake in murine bone marrow-derived macrophages. The LPNPs varied in diameter from 232 to 812 nm, in storage modulus from 21.

Hydrogel foam dressings with angiogenic and immunomodulatory factors from mesenchymal stem cells.

Stem cell therapy and skin substitutes address the stalled healing of chronic wounds in order to promote wound closure; however, the high cost and regulatory hurdles of these treatments limit patient access. A low-cost method to induce bioactive healing has the potential to substantially improve patient care and prevent wound-induced limb loss. A previous study reported that bioactive factors derived from apoptotic-like mesenchymal stem cells (MSCs) demonstrated anti-inflammatory and proangiogenic effects and improved ischemic muscle regeneration.

Oxidative Degradation of Sequence-Defined Peptoid Oligomers.

Due to their N-substitution, peptoids are generally regarded as resistant to biological degradation, such as enzymatic and hydrolytic mechanisms. This stability is an especially attractive feature for therapeutic development and is a selling point of many previous biological studies. However, another key mode of degradation remains to be fully explored, namely oxidative degradation mediated by reactive oxygen and nitrogen species (ROS/RNS).

Soluble components from mesenchymal stromal cell processing exert anti-inflammatory effects and facilitate ischemic muscle regeneration.

Background Aims: Skeletal muscle regeneration after severe damage is reliant on local stem cell proliferation and differentiation, processes that are tightly regulated by macrophages. Peripheral artery disease is a globally prevalent cardiovascular disease affecting millions of people. Progression of the disease leads to intermittent claudication, subsequent critical limb ischemia and muscle injury.

Apoptotic body-inspired nanoparticles target macrophages at sites of inflammation to support an anti-inflammatory phenotype shift.

Chronic inflammation is a significant pathological process found in a range of disease states. Treatments to reduce inflammation in this family of diseases may improve symptoms and disease progression, but are largely limited by variable response rates, cost, and off-target effects. Macrophages are implicated in many inflammatory diseases for their critical role in the maintenance and resolution of inflammation.

Controlling Nucleopeptide Hydrogel Self-Assembly and Formation for Cell-Culture Scaffold Applications.

Hydrogels made from self-assembling peptides have significant advantages in tissue engineering, namely a biocompatible nature and large molecular repertoire. Short peptides in particular allow for straightforward synthesis, self-assembly, and reproducibility. Applications are currently limited, however, due to potential toxicity of the chemical modifications that drive self-assembly and harsh gelation conditions.

Laser nanobubbles induce immunogenic cell death in breast cancer.

Recent advances in immunotherapy have highlighted a need for therapeutics that initiate immunogenic cell death in tumors to stimulate the body's immune response to cancer. This study examines whether laser-generated bubbles surrounding nanoparticles ("nanobubbles") induce an immunogenic response for cancer treatment. A single nanosecond laser pulse at 1064 nm generates micron-sized bubbles surrounding gold nanorods in the cytoplasm of breast cancer cells.

Cell-Inspired Biomaterials for Modulating Inflammation.

Inflammation is a crucial part of wound healing and pathogen clearance. However, it can also play a role in exacerbating chronic diseases and cancer progression when not regulated properly. A subset of current innate immune engineering research is focused on how molecules such as lipids, proteins, and nucleic acids native to a healthy inflammatory response can be harnessed in the context of biomaterial design to promote healing, decrease disease severity, and prolong survival.

A Model for Studying the Biomechanical Effects of Varying Ratios of Collagen Types I and III on Cardiomyocytes.

Purpose: To develop a novel model composed solely of Col I and Col III with the lower and upper limits set to include the ratios of Col I and Col III at 3:1 and 9:1 in which the structural and mechanical behavior of the resident CM can be studied. Further, the progression of fibrosis due to change in ratios of Col I:Col III was tested.

Methods: Collagen gels with varying Col I:Col III ratios to represent a healthy (3:1) and diseased myocardial tissue were prepared by manually casting them in wells.

Hydrogel scaffolds with elasticity-mimicking embryonic substrates promote cardiac cellular network formation.

Hydrogels are a class of biomaterials used for a wide range of biomedical applications, including as a three-dimensional (3D) scaffold for cell culture that mimics the extracellular matrix (ECM) of native tissues. To understand the role of the ECM in the modulation of cardiac cell function, alginate was used to fabricate crosslinked gels with stiffness values that resembled embryonic (2.66 ± 0.

Thin-Film Freeze-Drying Is a Viable Method to Convert Vaccines Containing Aluminum Salts from Liquid to Dry Powder.

Aluminum salts are used as an adjuvant in many human and veterinary vaccines. However, aluminum salt-adjuvanted vaccines are sensitive to temperature change and must be stored at 2-8 °C. Inadvertently exposing them to slow freezing temperatures can cause irreversible aggregation of aluminum salt microparticles and loss of potency and/or immunogenicity of the vaccines.

Poly-d-lysine coated nanoparticles to identify pro-inflammatory macrophages.

Identifying pro-inflammatory macrophages (M1) is of immense importance to diagnose, monitor, and treat various pathologies. In addition, adoptive cell therapies, where harvested cells are isolated, modified to express an M1-like phenotype, then re-implanted to the patient, are also becoming more prevalent to treat diseases such as cancer. In a step toward identifying, labeling, and monitoring macrophage phenotype for adoptive cell therapies, we developed a reactive oxygen species (ROS)-sensitive, gold nanoparticle (AuNP) that fluorescently labels M1 macrophages.

Dynamic extracellular matrix stiffening induces a phenotypic transformation and a migratory shift in epithelial cells.

Soft tissue tumors, including breast cancer, become stiffer throughout disease progression. This increase in stiffness has been shown to correlate to malignant phenotype and epithelial-to-mesenchymal transition (EMT) in vitro. Unlike current models, utilizing static increases in matrix stiffness, our group has previously created a system that allows for dynamic stiffening of an alginate-matrigel composite hydrogel to mirror the native dynamic process.

Self-assembled nucleo-tripeptide hydrogels provide local and sustained doxorubicin release.

Self-assembled nucleo-peptide hydrogels have a nanofibril structure composed of noncovalent molecular interactions between peptide groups as well as π-π stacking and Watson-Crick interactions via complementary nucleobases. These hydrogels have specific benefits for biomedical applications due to their DNA-like interactions in addition to the well-known advantages of peptide biomaterials: biocompatibility, extracellular matrix (ECM)-like structure, and bottom-up design. Inspired by the nucleobase stacking structure, we hypothesized that nucleo-peptides would be able to deliver the DNA-intercalating chemotherapeutic, doxorubicin (Dox) in a sustained manner when delivered locally to a solid tumor.

A Visible Light-Cross-Linkable, Fibrin-Gelatin-Based Bioprinted Construct with Human Cardiomyocytes and Fibroblasts.

In this study, fibrin was added to a photo-polymerizable gelatin-based bioink mixture to fabricate cardiac cell-laden constructs seeded with human induced pluripotent stem cell-derived cardiomyocytes (iPS-CM) or CM cell lines with cardiac fibroblasts (CF). The extensive use of platelet-rich fibrin, its capacity to offer patient specificity, and the similarity in composition to surgical glue prompted us to include fibrin in the existing bioink composition. The cell-laden bioprinted constructs were cross-linked to retain a herringbone pattern via a two-step procedure including the visible light cross-linking of furfuryl-gelatin followed by the chemical cross-linking of fibrinogen via thrombin and calcium chloride.

Modulating inflammatory macrophages with an apoptotic body-inspired nanoparticle.

Macrophages play a critical role in the initiation, maintenance, and resolution of inflammation because of their diverse and plastic phenotypic responses to extracellular stimuli. Inflammatory stimuli drive the recruitment and activation of inflammatory (M1) macrophages, capable of significant cytokine production that potentiates inflammation. Local environmental signals including apoptotic cell efferocytosis drive a phenotypic transition toward pro-reparative (M2) macrophages to facilitate the resolution of inflammation.

Design and Characterization of Nucleopeptides for Hydrogel Self-Assembly.

Self-assembling peptides can be used in a bottom-up approach to build hydrogels that are similar to the extracellular matrix at both structural and functional levels. In this study, a nucleo-tripeptide library was constructed to identify molecules that form hydrogels under physiological conditions. We used both experimental and computational approaches to study these self-assembled structures.

Photoacoustic Tracking of Mesenchymal Stem Cell Viability.

Adult stem cell therapy has demonstrated improved outcomes for treating cardiovascular diseases in preclinical trials. The development of imaging tools may increase our understanding of the mechanisms of stem cell therapy, and a variety of imaging tools have been developed to image transplanted stem cells ; however, they lack the ability to interrogate stem cell function longitudinally. Here, we report the use of a nanoparticle-based contrast agent that can track stem cell viability using photoacoustic imaging.

A Comparative Study of a 3D Bioprinted Gelatin-Based Lattice and Rectangular-Sheet Structures.

3D bioprinting holds great promise in the field of regenerative medicine as it can create complex structures in a layer-by-layer manner using cell-laden bioinks, making it possible to imitate native tissues. Current bioinks lack both high printability and biocompatibility required in this respect. Hence, the development of bioinks that exhibit both properties is needed.

Phenotypic Basis for Matrix Stiffness-Dependent Chemoresistance of Breast Cancer Cells to Doxorubicin.

The persistence of drug resistant cell populations following chemotherapeutic treatment is a significant challenge in the clinical management of cancer. Resistant subpopulations arise via both cell intrinsic and extrinsic mechanisms. Extrinsic factors in the microenvironment, including neighboring cells, glycosaminoglycans, and fibrous proteins impact therapy response.

Design and Evaluation of Short Self-Assembling Depsipeptides as Bioactive and Biodegradable Hydrogels.

Described herein is the design of a cell-adherent and degradable hydrogel. Our goal was to create a self-assembling, backbone ester-containing analogue of the cell adhesion motif, arginine-glycine-aspartic acid (RGD). Two depsipeptides containing Fmoc (-(fluorenyl)-9-methoxycarbonyl), Fmoc-FR-Glc-D, and Fmoc-F-Glc-RGD (where "Glc" is glycolic acid) were designed based on the results of integrin-binding affinity and cell interaction analyses.

The applicability of furfuryl-gelatin as a novel bioink for tissue engineering applications.

Three-dimensional bioprinting is an innovative technique in tissue engineering, to create layer-by-layer structures, required for mimicking body tissues. However, synthetic bioinks do not generally possess high printability and biocompatibility at the same time. So, there is an urgent need for naturally derived bioinks that can exhibit such optimized properties.

Recruitment and therapeutic application of macrophages in skeletal muscles after hind limb ischemia.

Objective: Peripheral arterial disease can cause not only ischemia but also skeletal muscle damage. It has been known that macrophages (MPs) play an important role in coordinating muscle repair; however, phenotype transition of monocyte-MP in ischemic muscle has not been well defined. Hence, the purpose of this study was to examine the temporal recruitment of MPs and to explore their therapeutic effect on ischemic muscle regeneration.

Electrospun poly(N-isopropyl acrylamide)/poly(caprolactone) fibers for the generation of anisotropic cell sheets.

Cell alignment in muscle, nervous tissue, and cartilage is requisite for proper tissue function; however, cell sheeting techniques using the thermosensitive polymer poly(N-isopropyl acrylamide) (PNIPAAm) can only produce anisotropic cell sheets with delicate and resource-intensive modifications. We hypothesized that electrospinning, a relatively simple and inexpensive technique to generate aligned polymer fibers, could be used to fabricate anisotropic PNIPAAm and poly(caprolactone) (PCL) blended surfaces that both support cell viability and permit cell sheet detachment via PNIPAAm dissolution. Aligned electrospun PNIPAAm/PCL fibers (0%, 25%, 50%, 75%, 90%, and 100% PNIPAAm) were electrospun and characterized.