Fine‐Tunable and Injectable 3D Hydrogel for On‐Demand Stem Cell Niche

Abstract

Stem‐cell‐based tissue engineering requires increased stem cell retention, viability, and control of differentiation. The use of biocompatible scaffolds encapsulating stem cells typically addresses the first two problems. To achieve control of stem cell fate, fine‐tuned biocompatible scaffolds with bioactive molecules are necessary. However, given that the fine‐tuning of stem cell scaffolds is associated with UV irradiation and in situ scaffold gelation, this process is in conflict with injectability. Herein, a fine‐tunable and injectable 3D hydrogel system is developed with the use of thermosensitive poly(organophosphazene) bearing β‐cyclodextrin (β‐CD PPZ) and two types of adamantane‐peptides (Ad‐peptides) that are associated with mesenchymal stem cell (MSC) differentiation and that serve as stoichiometrically controlled pendants for fine‐tuning. Given that complexation of hosts and guests subject to strict stoichiometric control is achieved with simple mixing, these fabricated hydrogels exhibit well‐aligned, fine‐tuning responses, even in living animals. Injection of MSCs in fine‐tuned hydrogels also results in various chondrogenic differentiation levels at three weeks postinjection. This is attributed to the differential controls of Ad‐peptides, if MSC preconditioning is excluded. Eventually, the fine‐tunable and injectable 3D hydrogel could be applied as platform technology by simply switching the types of peptides bearing adamantane and their stoichiometry.

Advances in the Application of Supramolecular Hydrogels for Stem Cell Delivery and Cartilage Tissue Engineering

“…Injection of MSCs encapsulated in this fine-tuned hydrogel triggered various chondrogenic differentiation stages in 3 weeks post-injection by the stoichiometrically strict control of Ad-peptides based on host–guest interaction. Thus, simply changing the adamantane-bearing peptide and its stoichiometry, the adjustable and injectable 3D hydrogel can be used as a platform technology for on-demand stem cell niche ( Hong et al, 2019 ).…”

“…The fate of the MSCs can be controlled by varying the stoichiometric ratio of the different molecules. Adapted with permission from Hong et al (2019) .…”

Injectable polymeric nanoparticle hydrogel system for long-term anti-inflammatory effect to treat osteoarthritis

“…A hybrid system of nanoscaled drug delivery and 3D hydrogel formation could fulfill the requirements of a powerful tool for successful OA treatment. For this purpose, a poly(organophosphazenes), which has substituted hydrophobic and hydrophilic side chains, could be a good candidate as an injectable in situ hydrogel-forming, and biodegradable drug delivery carrier with favorable drug loading process and long-term drug release characteristics [ [34] , [35] , [36] ]. In an aqueous solution, the polymer exists in the form of unfolded chains or nanosized spherical particles according to changes in hydrophobicity with temperature alterations [ 37 , 38 ].…”

Dual stimuli-responsive polyphosphazene-based molecular gates for controlled drug delivery in lung cancer cells

“…7 Of these, polyphosphazenes 8 are quite advanced in biomedical applications, 9,10 with uorinated derivatives having FDA approval as stent coatings 11 and vaccine adjuvants in advanced clinical trials. 12,13 Thermoresponsive polyphosphazenes have been extensively investigated, in particular for their use as thermosensitive injectable hydrogels, with, among others, delivery or siRNA for gene silencing, stem cell delivery 14 and combinatorial cancer therapy. 15 Due to a widely observed phenomenon for amphiphilic polymers, 16,17 thermoresponsive polymers commonly possess a lower critical solution temperature (LCST) in aqueous solutions, above which the macromolecules collapse, followed oen by agglomeration and/or gelation.…”