Characterizing influence of rCHOP treatment on diffuse large B-cell lymphoma microenvironment through in vitro microfluidic spheroid model.

For over two decades, Rituximab and CHOP combination treatment (rCHOP) has remained the standard treatment approach for diffuse large B-cell lymphoma (DLBCL). Despite numerous clinical trials exploring treatment alternatives, few options have shown any promise at further improving patient survival and recovery rates. A wave of new therapeutic approaches have recently been in development with the rise of immunotherapy for cancer, however, the cost of clinical trials is prohibitive of testing all promising approaches.

Cyclic Thiosulfinates as a Novel Class of Disulfide Cleavable Cross-Linkers for Rapid Hydrogel Synthesis.

We recently reported that cyclic thiosulfinates are cysteine selective cross-linkers that avoid the "dead-end" modifications that contribute to other cross-linkers' toxicity. In this study, we generalize the chemistry of cyclic thiosulfinates to that of thiol selective cross-linking and apply them to the synthesis of hydrogels. Thiol-functionalized four-arm poly(ethylene glycol) and hyaluronic acid monomers were cross-linked with 1,2-dithiane-1-oxide to form disulfide cross-linked hydrogels within seconds.

Thiolated Thermoresponsive Polymer Scaffolds with Tunable Mucoadhesivity for Intestinal Applications.

Treatments for inflammatory bowel disease largely involve lifelong drug prescriptions or surgical intervention that can lead to poor quality of life for patients. Regenerative therapies involving stem cells have been shown to induce tissue regeneration but are limited in their efficacy by inefficient delivery mechanisms. Scaffold-based delivery of cells has been a key research focus of tissue engineers seeking to translate advances in stem cell research into clinical solutions.

Spray Delivery of Intestinal Organoids to Reconstitute Epithelium on Decellularized Native Extracellular Matrix.

The native extracellular matrix (ECM) serves as a unique platform for tissue engineering because it provides an organ-specific scaffold in terms of both matrix composition and tissue architecture. However, efficacious cell-seeding techniques for recellularizing the ECM constructs with appropriate cell types to restore biological function remain under development. In this study, the impact of spraying as a seeding technique for repopulation of decellularized small intestine was investigated.

Free Epoxide Content Mediates Encapsulated Cell Viability and Activity through Protein Interactions in a Thermoresponsive, In Situ Forming Hydrogel.

The development of synthetic and well-defined extracellular matrices that are free of xenogeneic components and are capable of inducing desired cellular responses holds great potential for use in vitro as 3D cell culture environments and in vivo as scaffolds for tissue regeneration. In this study, the impact of free and partially occupied epoxide groups on the viability, activity, and behavior of rat fibroblasts encapsulated in thermoresponsive hydrogels based on poly(N-isopropylacrylamide) (pNiPAAm) was investigated. While fibroblasts encapsulated in neat pNiPAAm remained rounded and showed significant toxicity by 5 days, those encapsulated in the epoxide-modified thermogels demonstrated not only high viability but also an ability to proliferate, attach, produce extracellular matrix (ECM) components, and cluster.

In situ spray deposition of cell-loaded, thermally and chemically gelling hydrogel coatings for tissue regeneration.

In this study, the efficacy of creating cellular hydrogel coatings on warm tissue surfaces through the minimally invasive, sprayable delivery of thermoresponsive liquid solutions was investigated. Poly(N-isopropylacrylamide)-based (pNiPAAm) thermogelling macromers with or without addition of crosslinking polyamidoamine (PAMAM) macromers were synthesized and used to produce in situ forming thermally and chemically gelling hydrogel systems. The effect of solution and process parameters on hydrogel physical properties and morphology was evaluated and compared to poly(ethylene glycol) and injection controls.

In vitro and in vivo evaluation of self-mineralization and biocompatibility of injectable, dual-gelling hydrogels for bone tissue engineering.

In this study, we investigated the mineralization capacity and biocompatibility of injectable, dual-gelling hydrogels in a rat cranial defect as a function of hydrogel hydrophobicity from either the copolymerization of a hydrolyzable lactone ring or the hydrogel polymer content. The hydrogel system comprised a poly(N-isopropylacrylamide)-based thermogelling macromer (TGM) and a polyamidoamine crosslinker. The thermogelling macromer was copolymerized with (TGM/DBA) or without (TGM) a dimethyl-γ-butyrolactone acrylate (DBA)-containing lactone ring that modulated the lower critical solution temperature and thus, the hydrogel hydrophobicity, over time.

Mesenchymal stem cell and gelatin microparticle encapsulation in thermally and chemically gelling injectable hydrogels for tissue engineering.

In this work, we investigated the viability and osteogenic differentiation of mesenchymal stem cells encapsulated with gelatin microparticles (GMPs) in an injectable, chemically and thermally gelling hydrogel system combining poly(N-isopropylacrylamide)-based thermogelling macromers containing pendant epoxy rings with polyamidoamine-based hydrophilic and degradable diamine crosslinking macromers. Specifically, we studied how the parameters of GMP size and loading ratio affected the viability and differentiation of cells encapsulated within the hydrogel. We also examined the effects of cell and GMP co-encapsulation on hydrogel mineralization.

Synthesis, physicochemical characterization, and cytocompatibility of bioresorbable, dual-gelling injectable hydrogels.

Injectable, dual-gelling hydrogels were successfully developed through the combination of physical thermogellation at 37 °C and favorable amine:epoxy chemical cross-linking. Poly(N-isopropylacrylamide)-based thermogelling macromers with a hydrolyzable lactone ring and epoxy pendant groups and a biodegradable diamine-functionalized polyamidoamine cross-linker were synthesized, characterized, and combined to produce nonsyneresing and bioresorbable hydrogels. Differential scanning calorimetry and oscillatory rheometry demonstrated the rapid and dual-gelling nature of the hydrogel formation.

Perspectives on the interface of drug delivery and tissue engineering.

Controlled drug delivery of bioactive molecules continues to be an essential component of engineering strategies for tissue defect repair. This article surveys the current challenges associated with trying to regenerate complex tissues utilizing drug delivery and gives perspectives on the development of translational tissue engineering therapies which promote spatiotemporal cell-signaling cascades to maximize the rate and quality of repair.

Structure-property evaluation of thermally and chemically gelling injectable hydrogels for tissue engineering.

The impact of synthesis and solution formulation parameters on the swelling and mechanical properties of a novel class of thermally and chemically gelling hydrogels combining poly(N-isopropylacrylamide)-based thermogelling macromers containing pendant epoxy rings with polyamidoamine-based hydrophilic and degradable diamine cross-linking macromers was evaluated. Through variation of network hydrophilicity and capacity for chain rearrangement, the often problematic tendency of thermogelling hydrogels to undergo significant syneresis was addressed. The demonstrated ability to tune postformation dimensional stability easily at both the synthesis and formulation stages represents a significant novel contribution toward efforts to utilize poly(N-isopropylacrylamide)-based polymers as injectable biomaterials.

Synthesis and characterization of thermally and chemically gelling injectable hydrogels for tissue engineering.

Novel, injectable hydrogels were developed that solidify through a physical and chemical dual-gelation mechanism upon preparation and elevation of temperature to 37 °C. A thermogelling, poly(N-isopropylacrylamide)-based macromer with pendant epoxy rings and a hydrolytically degradable polyamidoamine-based diamine cross-linker were synthesized, characterized, and combined to produce in situ forming hydrogel constructs. Network formation through the epoxy-amine reaction was shown to be rapid and facile, and the progressive incorporation of the hydrophilic polyamidoamine cross-linker into the hydrogel was shown to mitigate the often problematic tendency of thermogelling materials to undergo significant postformation gel syneresis.

Extraction of hyperoside and quercitrin from mimosa (Albizia julibrissin) foliage.

Mimosa, an excellent energy crop candidate because of its high growth yield, also contains, on a dry basis, 0.83% hyperoside and 0.90% quercitrin.