Radical-Mediated Degradation of Thiol-Maleimide Hydrogels.

Michael addition between thiol- and maleimide-functionalized molecules is a long-standing approach used for bioconjugation, hydrogel crosslinking, and the functionalization of other advanced materials. While the simplicity of this chemistry enables facile synthesis of hydrogels, network degradation is also desirable in many instances. Here, the susceptibility of thiol-maleimide bonds to radical-mediated degradation is reported.

Poly(ethylene glycol)-Based Hydrogel Microcarriers Alter Secretory Activity of Genetically Modified Mesenchymal Stromal Cells.

In order to scale up culture therapeutic cells, such as mesenchymal stromal cells (MSCs), culture in suspension bioreactors using microcarriers (μCs) is preferred. However, the impact of microcarrier type on the resulting MSC secretory activity has not been investigated. In this study, two poly(ethylene glycol) hydrogel formulations with different swelling ratios (named "stiffer" and "softer") were fabricated as μC substrates to culture MSCs and MSCs genetically modified to express the interleukin-1 receptor antagonist (IL-1Ra-MSCs).

Moderate-Affinity Affibodies Modulate the Delivery and Bioactivity of Bone Morphogenetic Protein-2.

Uncontrolled bone morphogenetic protein-2 (BMP-2) release can lead to off-target bone growth and other adverse events. To tackle this challenge, yeast surface display is used to identify unique BMP-2-specific protein binders known as affibodies that bind to BMP-2 with different affinities. Biolayer interferometry reveals an equilibrium dissociation constant of 10.

Development and characterization of Factor Xa-responsive materials for applications in cell culture and biologics delivery.

Stimuli-responsive biomaterials may be used to better control the release of bioactive molecules or cells for applications involving drug delivery and controlled cell release. In this study, we developed a Factor Xa (FXa)-responsive biomaterial capable of controlled release of pharmaceutical agents and cells from in vitro culture. FXa-cleavable substrates were formed as hydrogels that degraded in response to FXa enzyme over several hours.

Tropism of the Novel AAVBR1 Capsid Following Subretinal Delivery.

A serious limitation of current adeno-associated viral (AAV) capsids employed for subretinal delivery is achieving adequate lateral spread beyond the injection site, required for the efficient delivery of gene therapy to the outer retina and/or RPE. AAVBR1 is a unique AAV with exceptional tropism for CNS microvasculature following systemic delivery. Here, we used in vivo and ex vivo analysis to show that subretinal delivery of AAVBR1.

Sodium alginate microencapsulation of human mesenchymal stromal cells modulates paracrine signaling response and enhances efficacy for treatment of established osteoarthritis.

Mesenchymal stromal cells (MSCs) have shown promise as osteoarthritis (OA) treatments; however, effective translation has been limited by high variability and heterogeneity of MSCs, suboptimal delivery strategies, and poor understanding of critical quality and potency attributes. Furthermore, most pre-clinical studies of MSC therapeutics for OA have focused on delaying OA development and not on treating established OA, which brings added clinical relevance. Thus, the objective of the current study was to assess the effects of sodium alginate microencapsulation on human MSC (hMSC) secretion of immunomodulatory cytokines in an OA microenvironment and therapeutic efficacy in treating established OA.

Articular Cartilage- and Synoviocyte-Binding Poly(ethylene glycol) Nanocomposite Microgels as Intra-Articular Drug Delivery Vehicles for the Treatment of Osteoarthritis.

Intra-articular (IA) injection is an attractive route of administration for the treatment of osteoarthritis (OA). However, free drugs injected into the joint space are rapidly cleared and many of them can induce adverse off-target effects on different IA tissues. To overcome these limitations, we designed nanocomposite 4-arm-poly(ethylene glycol)-maleimide (PEG-4MAL) microgels, presenting cartilage- or synoviocyte-binding peptides, containing poly(lactic--glycolic) acid (PLGA) nanoparticles (NPs) as an IA small molecule drug delivery system.

Skin-interfaced microfluidic system with personalized sweating rate and sweat chloride analytics for sports science applications.

Advanced capabilities in noninvasive, in situ monitoring of sweating rate and sweat electrolyte losses could enable real-time personalized fluid-electrolyte intake recommendations. Established sweat analysis techniques using absorbent patches require post-collection harvesting and benchtop analysis of sweat and are thus impractical for ambulatory use. Here, we introduce a skin-interfaced wearable microfluidic device and smartphone image processing platform that enable analysis of regional sweating rate and sweat chloride concentration ([Cl]).

Biomaterial strategies for improved intra-articular drug delivery.

Osteoarthritis (OA) is a joint degenerative disease that has become one of the leading causes of disability in the world. It is estimated that OA affects 50 million adults in the United States. Currently, there are no FDA-approved treatments that slow OA progression and its treatment is limited to pain management strategies and life style changes.

Materials Science and Design Principles of Growth Factor Delivery Systems in Tissue Engineering and Regenerative Medicine.

Growth factors (GFs) are signaling molecules that direct cell development by providing biochemical cues for stem cell proliferation, migration, and differentiation. GFs play a key role in tissue regeneration, but one major limitation of GF-based therapies is dosage-related adverse effects. Additionally, the clinical applications and efficacy of GFs are significantly affected by the efficiency of delivery systems and other pharmacokinetic factors.