PEG-fibrinogen hydrogel microspheres as a scaffold for therapeutic delivery of immune cells

Abstract

Recent advances in the field of cell therapy have proposed new solutions for tissue repair and regeneration using various cell delivery approaches. Here we studied ex vivo a novel topical delivery system of encapsulated cells in hybrid polyethylene glycol-fibrinogen (PEG-Fb) hydrogel microspheres to respiratory tract models. We investigated basic parameters of cell encapsulation, delivery and release in conditions of inflamed and damaged lungs of bacterial-infected mice. The establishment of each step in the study was essential for the proof of concept. We demonstrated co-encapsulation of alveolar macrophages and epithelial cells that were highly viable and equally distributed inside the microspheres. We found that encapsulated macrophages exposed to bacterial endotoxin lipopolysaccharide preserved high viability and secreted moderate levels of TNFα, whereas non-encapsulated cells exhibited a burst TNFα secretion and reduced viability. LPS-exposed encapsulated macrophages exhibited elongated morphology and out-migration capability from microspheres. Microsphere degradation and cell release in inflamed lung environment was studied ex vivo by the incubation of encapsulated macrophages with lung extracts derived from intranasally infected mice with Yersinia pestis, demonstrating the potential in cell targeting and release in inflamed lungs. Finally, we demonstrated microsphere delivery to a multi-component airways-on-chip platform that mimic human nasal, bronchial and alveolar airways in serially connected compartments. This study demonstrates the feasibility in using hydrogel microspheres as an effective method for topical cell delivery to the lungs in the context of pulmonary damage and the need for tissue repair.

Development of a local controlled release system for therapeutic proteins in the treatment of skeletal muscle injuries and diseases

“…There are several methods used to produce hydrogel microcarriers in the form of microspheres that are sufficiently small to enable such injectability, including microfluidic polymerization, emulsion-polymerization, and drop-wise polymerization [ 69 ]. In this study, the PF microspheres were fabricated using a water-in-oil emulsion-polymerization method, which has previously been shown to efficiently encapsulate mRNA and viable cells in PF microspheres [ 59 , 66 , 70 , 71 ] The estimated dimensions of the microspheres, in the range of 100 micrometers, were compatible with intramuscular administration procedures [ 72 ]. Although the dual-photoinitiator aqueous-oil emulsion polymerization technique worked well for producing very small PF microspheres, there are several limitations to this approach.…”

Injectable Near-Infrared Photothermal Responsive Drug-Loaded Multiwalled Carbon Nanotube Hydrogels for Spinal Cord Injury Repair

“…38,41 Hydrogel microspheres hold great promise for tissue repair applications, such as cellular and drug therapy delivery. 14,42 In this study, GG was selected to prepare the hydrogel microspheres. GG is a thermosensitive hydrogel scaffold that is a transparent solution at elevated temperatures and a transparent solid at low temperatures.…”

“…Further on, [PTX/VEGF]@DMWCNTs/GG microspheres were prepared by microfluidic technology. Compared with other methods for microsphere fabrication such as single emulsion, phase separation, spray drying, and membrane emulsification, microfluidic technology has many advantages, such as the ability to control microsphere shape and size, high drug loading capacity, and control over the physical and chemical properties of microspheres by manipulating solvent type and polymer concentration. , Hydrogel microspheres hold great promise for tissue repair applications, such as cellular and drug therapy delivery. , In this study, GG was selected to prepare the hydrogel microspheres. GG is a thermosensitive hydrogel scaffold that is a transparent solution at elevated temperatures and a transparent solid at low temperatures. , GG possesses unique physical and chemical properties, such as the ability to form a gel through both thermal and ion-cross-linking mechanisms. , In this study, Ca 2+ was used to induce GG gelation.…”

Hydrogel Microparticles for Bone Regeneration

“…Furthermore, the release profile has been reported to differ between monodisperse and polydisperse HMPs, with monodisperse microparticles exhibiting a significantly reduced burst release compared to their polydisperse counterparts [41]. Collecting a specific size of HMPs can be achieved using sieves [42] or filters [43].…”