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RNA-based therapeutics have shown tremendous promise in disease intervention at the genetic level, and some have been approved for clinical use, including the recent COVID-19 messenger RNA vaccines. The clinical success of RNA therapy is largely dependent on the use of chemical modification, ligand conjugation or non-viral nanoparticles to improve RNA stability and facilitate intracellular delivery. Unlike molecular-level or nanoscale approaches, macroscopic hydrogels are soft, water-swollen three-dimensional structures that possess remarkable features such as biodegradability, tunable physiochemical properties and injectability, and recently they have attracted enormous attention for use in RNA therapy. Specifically, hydrogels can be engineered to exert precise spatiotemporal control over the release of RNA therapeutics, potentially minimizing systemic toxicity and enhancing in vivo efficacy. This Review provides a comprehensive overview of hydrogel loading of RNAs and hydrogel design for controlled release, highlights their biomedical applications and offers our perspectives on the opportunities and challenges in this exciting field of RNA delivery., (© 2023. Springer Nature Limited.)

Towards the repair of damaged tissues, numerous scaffolds have been fabricated to recreate the complex extracellular matrix (ECM) environment to support desired cell behaviors; however, it is often challenging to design scaffolds with the requisite cell-anchorage sites, mechanical stability, and tailorable physicochemical properties necessary for many applications. To address this and to improve on the properties of hyaluronic acid (HA) hydrogels, we combined photocrosslinkable norbornene-modified HA (NorHA) with human platelet lysate (PL). These PL-NorHA hybrid hydrogels supported the adhesion of cells when compared to NorHA hydrogels without PL, exhibited tailorable physicochemical properties based on the concentration of individual components, and released proteins over time. Using microfluidic techniques with on-chip mixing of NorHA and PL and subsequent photocrosslinking, spherical PL-NorHA microgels with a hierarchical fibrillar network were fabricated that exhibited the sustained delivery of PL proteins. Microgels could be jammed into granular hydrogels that exhibited shear-thinning and self-healing properties, enabling ejection from syringes and the fabrication of stable 3D constructs with 3D printing. Again, the inclusion of PL enhanced cellular interactions with the microgel structures. Overall, the combination of biomolecules and fibrin self-assembly arising from the enriched milieu of PL-derived proteins improved the bioactivity of HA-based hydrogels, enabling the formation of dynamic systems with modular design. The granular systems can be engineered to meet the complex demands of functional tissue repair using versatile processing techniques, such as with 3D printing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Photocrosslinkable magnetic hydrogels are attracting great interest for tissue engineering strategies due to their versatility and multifunctionality, including their remote controllability ex vivo, thus enabling engineering complex tissue interfaces. This study reports the development of a photocrosslinkable magnetic responsive hydrogel made of methacrylated chondroitin sulfate (MA-CS) enriched with platelet lysate (PL) with tunable features, envisioning their application in tendon-to-bone interface. MA-CS coated iron-based magnetic nanoparticles were incorporated to provide magnetic responsiveness to the hydrogel. Osteogenically differentiated adipose-derived stem cells and/or tendon-derived cells were encapsulated within the hydrogel, proliferating and expressing bone- and tendon-related markers. External magnetic field (EMF) application modulated the swelling, degradation and release of PL-derived growth factors, and impacted both cell morphology and the expression and synthesis of tendon- and bone-like matrix with a more evident effect in co-cultures. Overall, the developed magnetic responsive hydrogel represents a potential cell carrier system for interfacial tissue engineering with EMF-controlled properties., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The extracellular matrix (ECM)-biomimetic fibrillar structure of platelet lysate (PL) gels along with their enriched milieu of biomolecules has drawn significant interest in regenerative medicine applications. However, PL-based gels have poor structural stability, which severely limits their performance as a bioinstructive biomaterial. Here, rod-shaped cellulose nanocrystals (CNC) are used as a novel approach to modulate the physical and biochemical microenvironment of PL gels enabling their effective use as injectable human-based cell scaffolds with a level of biomimicry that is difficult to recreate with synthetic biomaterials. The incorporation of CNC (0 to 0.61 wt%) into the PL fibrillar network during the coagulation cascade leads to decreased fiber branching, increased interfiber porosity (from 66 to 83%) and modulates fiber (from 1.4 ± 0.7 to 27 ± 12 kPa) and bulk hydrogel (from 18 ± 4 to 1256 ± 82 Pa) mechanical properties. As a result of these physicochemical alterations, nanocomposite PL hydrogels resist the typical extensive clot retraction (from 76 ± 1 to 24 ± 3 at day 7) and show favored retention of PL bioactive molecules. The feedback of these cues on the fate of human adipose-derived stem cells is evaluated, showing how it can be explored to modulate the commitment of encapsulated stem cells toward different genetic phenotypes without the need for additional external biological stimuli. These fibrillar nanocomposite hydrogels allow therefore the exploration of the outstanding biological properties of human-based PL as an efficient engineered ECM which can be tailored to trigger specific regenerative pathways in minimal invasive strategies.

The article focuses on the development of a biomimetic hydrogel, called EKGel, as an alternative to basement membrane extract (BME) for cultivating patient-derived breast tumor organoids (PDOs). Topics include the properties and advantages of EKGel, its effectiveness in supporting breast PDOs, and its potential applications in cancer research and drug development, offering improved stability and reduced contamination compared to BME-based cultures.

Abstract Photocrosslinkable magnetic hydrogels are attracting great interest for tissue engineering strategies due to their versatility and multifunctionality, including their remote controllability ex vivo , thus enabling engineering complex tissue interfaces. This study reports the development of a photocrosslinkable magnetic responsive hydrogel made of methacrylated chondroitin sulfate (MA-CS) enriched with platelet lysate (PL) with tunable features, envisioning their application in tendon-to-bone interface. MA-CS coated iron-based magnetic nanoparticles were incorporated to provide magnetic responsiveness to the hydrogel. Osteogenically differentiated adipose-derived stem cells and/or tendon-derived cells were encapsulated within the hydrogel, proliferating and expressing bone- and tendon-related markers. External magnetic field (EMF) application modulated the swelling, degradation and release of PL-derived growth factors, and impacted both cell morphology and the expression and synthesis of tendon- and bone-like matrix with a more evident effect in co-cultures. Overall, the developed magnetic responsive hydrogel represents a potential cell carrier system for interfacial tissue engineering with EMF-controlled properties. Graphical Abstract A versatile magnetic responsive hydrogel of methacrylated chondroitin sulfate (MA-CS) incorporating iron-based superparamagnetic nanoparticles (MA-CS MNPs) and enriched with platelet lysate was successfully developed. The modulation of intrinsic properties like swelling, degradation and release of platelet lysate-origin growth factors were controlled upon the actuation of an external magnetic field (EMF). Tendon-to-bone magnetic responsive hydrogels units were assembled encapsulating tendon derived cells (TDCs), osteogenically differentiated adipose derived stem cells (O-ASCs) and a co-culture of both under EMF stimulation aiming at interfacial approaches. The developed magnetic system represents a potential cell carrier system for interfacial tissue engineering with EMF-controlled properties. Image 2 [ABSTRACT FROM AUTHOR]