3D Culture of Adipose-Tissue-Derived Stem Cells Mainly Leads to Chondrogenesis in Poly(ethylene glycol)-Poly(l-alanine) Diblock Copolymer Thermogel

Abstract

Poly(ethylene glycol)-b-poly(L-alanine) (PEG-L-PA)s with L-PA molecular weights of 620, 1100, and 2480 Da and a fixed molecular weight of PEG at 5000 Da were synthesized to compare the thermosensitive behavior, and to investigate their potential as a three-dimensional (3D) culture matrix of adipose-tissue-derived stem cells (ADSCs). The sol-to-gel transition temperature and the concentration ranges where the transition was observed decreased as the L-PA molecular weight increased. ADSCs were cultured in the 3D matrixes of in situ formed PEG-L-PA hydrogels, which were produced by increasing the temperature of cell-suspended PEG-L-PA aqueous solutions. The spherical morphology was maintained in the PEG-L-PA hydrogel, while the cells underwent fibroblastic morphological changes in the Matrigel over 14 days of incubation. ADSCs exhibited high expression of type II collagen in the PEG-L-PA thermogel. In addition, they also moderately expressed the biomarker of myogenic differentiation factor 1 as the same mesodermal lineages, as well as the type III β-tubulin as a cross-differentiation biomarker. Similar to the in vitro study, the ADSCs predominantly exhibited chondrogenic biomarkers in the in vivo study. The study demonstrates that the polypeptide thermogel of PEG-L-PA is promising as a 3D culture matrix of ADSCs and as an injectable tissue engineering biomaterial.

Sustained intravitreal delivery of dexamethasone using an injectable and biodegradable thermogel

“…The use of organic solvents is thoroughly avoided during the whole process of application. So far, thermogelling PEG/polyester block copolymers [22][23][24][25][26][27], PEG/polypeptide block copolymers [28,29] and poly(phosphazenes) [30,31] have been reported.…”

Thermogelling Polymer–Platinum(IV) Conjugates for Long-Term Delivery of Cisplatin

“…2,6−13 Generally, these materials exhibited injectable sol states at low or room temperature and could spontaneously transform into gel states at the injection sites due to heating. 2,14−16 Typically biodegradable thermogels were composed of PEG/polyester block copolymers, 17−21 PEG/polypeptide block copolymers, 15,22 and poly-(phosphazenes). 23,24 These amphiphilic thermogelling polymers self-assemble into micelles in water, and further, micellar aggregation upon heating leads to thermogelation.…”

Microsphere‐Incorporated Hybrid Thermogel for Neuronal Differentiation of Tonsil Derived Mesenchymal Stem Cells

“…[ 27,28 ] Based on the methyl peak (1.4-1.9 ppm) and PEG peak (3.8-4.2 ppm) in the 1 H NMR spectra of the polymer, the polymer molecular weight were calculated to be 1000-795 ( Figure S1a, Supporting Information). The gel permeation chromatography exhibited the unimodal distribution of the polymer, where the number average molecular weight and molecular weight distribution calculated against PEG standards were 1, 100, and 1.1, respectively ( Figure S1b, Supporting Information).…”

“…[ 27,28 ] N -carboxy anhydrides of L -alanine were polymerized on the α-amino-ω-methoxy PEG. α-amino-ω-methoxy PEG (5.0 g, 5.0 mmole; M w 1000 Da) and N -carboxy anhydrides of L -alanine (10.2 g, 88.7 mmole) were used as a feed.…”