stepwise-cell-seeding-on-tessellated-scaffolds-to-study-sprouting

Stepwise Cell Seeding on Tessellated Scaffolds to Study Sprouting Blood Vessels

The cardiovascular system is a key player in human physiology, providing nourishment to most tissues in the body; vessels are present in different sizes, ...

University of Michigan, Ann Arbor

Compartmentalized particles enable co-presentation of dissimilar sets of properties, thereby offering a broad design space for multifunctional particles. Electrohydrodynamic co-jetting is a simple, yet versatile fabrication technique that can be used to prepare such multicompartmental particles and fibers. Processing conditions are summarized for co-jetting of aqueous and organic polymer solutions as well as nanoparticle suspensions. Because particles can comprise distinct polymers in different compartments, selective surface modification becomes possible. The latter can result in unidirectional interactions with cells or may pave new routes towards targeted drug delivery.

Recent progress in nano-biotechnology: compartmentalized micro- and nanoparticles via electrohydrodynamic co-jetting.

In the last several decades, research in the field of drug delivery has been challenged with the fabrication of carrier systems engineered to deliver therapeutics to the target site with sustained and controlled release kinetics. Herein, we report the fabrication of microparticles composed of two distinct compartments: i) one compartment containing a pH responsive polymer, acetal-modified dextran, and PLGA (polylactide-co-glycolide), and ii) one compartment composed entirely of PLGA. We demonstrate the complete release of dextran from the microparticles during a 10-hour period in an acidic pH environment and the complete degradation of one compartment in less than 24h. This is in congruence with the stability of the same microparticles in neutral pH over the 24-hour period. Such microparticles can be used as pH responsive carrier systems for drug delivery applications where their cargo will only be released when the optimum pH window is reached. The feasibility of the microparticle system for such an application was confirmed by encapsulating a cancer therapeutic, irinotecan, in the compartment containing the acetal-modified dextran polymer and the pH dependent release over a 5-day period was studied. It was found that upon pH change to an acidic environment, over 50% of the drug was first released at a rapid rate for 10h, similar to that observed for the dextran release, before continuing at a more controlled rate for 4 days. As such, these microparticles can play an important role in the fabrication of novel drug delivery systems due to the selective, controlled, and pH responsive release of their encapsulated therapeutics.

Multimodal delivery of irinotecan from microparticles with two distinct compartments.

The cellular microenvironment is extremely complex, and a plethora of materials and methods have been employed to mimic its properties in vitro. In particular, scientists and engineers have taken an interdisciplinary approach in their creation of synthetic biointerfaces that replicate chemical and physical aspects of the cellular microenvironment. Here the focus is on the use of synthetic materials or a combination of synthetic and biological ligands to recapitulate the defined surface chemistries, microstructure, and function of the cellular microenvironment for a myriad of biomedical applications. Specifically, strategies for altering the surface of these environments using self-assembled monolayers, polymer coatings, and their combination with patterned biological ligands are explored. Furthermore, methods for augmenting an important physical property of the cellular microenvironment, topography, are highlighted, and the advantages and disadvantages of these approaches are discussed. Finally, the progress of materials for prolonged stem cell culture, a key component in the translation of stem cell therapeutics for clinical use, is featured.

Current Trends and Challenges in Biointerfaces Science and Engineering.

Extrusion, electrospinning, and microdrawing are widely used to create fibrous polymer mats, but these approaches offer limited access to oriented arrays of nanometer-scale fibers with controlled size, shape, and lateral organization. We show that chemical vapor polymerization can be performed on surfaces coated with thin films of liquid crystals to synthesize organized assemblies of end-attached polymer nanofibers. The process uses low concentrations of radical monomers formed initially in the vapor phase and then diffused into the liquid-crystal template. This minimizes monomer-induced changes to the liquid-crystal phase and enables access to nanofiber arrays with complex yet precisely defined structures and compositions. The nanofiber arrays permit tailoring of a wide range of functional properties, including adhesion that depends on nanofiber chirality.

Templated nanofiber synthesis via chemical vapor polymerization into liquid crystalline films.

Glioblastoma (GBM), the most aggressive form of brain cancer, has witnessed very little clinical progress over the last decades, in part, due to the absence of effective drug delivery strategies. Intravenous injection is the least invasive drug delivery route to the brain, but has been severely limited by the blood-brain barrier (BBB). Inspired by the capacity of natural proteins and viral particulates to cross the BBB, we engineered a synthetic protein nanoparticle (SPNP) based on polymerized human serum albumin (HSA) equipped with the cell-penetrating peptide iRGD. SPNPs containing siRNA against Signal Transducer and Activation of Transcription 3 factor (STAT3i) result in in vitro and in vivo downregulation of STAT3, a central hub associated with GBM progression. When combined with the standard of care, ionized radiation, STAT3i SPNPs result in tumor regression and long-term survival in 87.5% of GBM-bearing mice and prime the immune system to develop anti-GBM immunological memory.

Article	Year
Recent progress in nano-biotechnology: compartmentalized micro- and nanoparticles via electrohydrodynamic co-jetting. Small (Weinheim an der Bergstrasse, Germany)\| PubMed ID: 21480519	2011
Multimodal delivery of irinotecan from microparticles with two distinct compartments. Journal of controlled release : official journal of the Controlled Release Society\| PubMed ID: 23973814	2013
Current Trends and Challenges in Biointerfaces Science and Engineering. Annual review of chemical and biomolecular engineering\| PubMed ID: 26247290	2015
Templated nanofiber synthesis via chemical vapor polymerization into liquid crystalline films. Science (New York, N.Y.)\| PubMed ID: 30442805	2018
Systemic brain tumor delivery of synthetic protein nanoparticles for glioblastoma therapy. Nature communications\| PubMed ID: 33173024	2020

Joerg Lahann

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