4.2.1. Polyethylene Glycol

Polyethylene glycol (PEG) is one of the most widely used synthetic polymers in the tissue engineering field. It is characterized by being chemically and biologically inert and by the high hydrophilicity of the polymer backbone. There is a wide range of polymer architectures and lengths that are commercially or synthetically accessible [181].

MSCs cultured on 3D thixotropic PEG-silica nanocomposite gel with high stiffness (≥75 Pa) expressed the highest level of Runx2 and osteocalcin. Additionally, RGD celladhesion peptide sequence immobilization in the gel of 75 Pa stiffness promoted ~13% higher expression of the osteogenic transcription factor [182]. Rat BMMSCs cultured on relatively soft (130 kPa) and stiff (3170 kPa) PEG hydrogels with RGD nano-spacings of 49 and 135 nm, incubated in the mixed osteogenic and adipogenic medium, exhibited a higher density of adherent MSCs, and osteogenesis was promoted on stiffer hydrogels. When the hydrogel stiffness was controlled, the large RGD nano-spacing was beneficial for osteogenesis, while the small RGD nano-spacing generated more adipogenesis [183].

Human MSCs were encapsulated in a multilayer PEG-based hydrogel composed of a soft cartilage-like layer of chondroitin sulfate (48 kPa) and low RGD concentrations, a stiff bone-like layer 345 kPa with high RGD concentrations, and an intermediate interfacial layer with 100 kPa. The recorded stiffness of the multilayer hydrogel was 90 kPa. Opposite to static conditions, dynamic mechanical stimulation generated a high expression of collagens with collagen II in the cartilage-like layer, collagen X in the interfacial layer, and collagen I in the bone-like layer with the presence of mineral deposits in the bone layer [184].

PEG/silk fibroin/HA (PEG/SF/HA) scaffold was prepared with varying HA concentrations, which influenced scaffold stiffness (80.98 to 190.51 kPa). PEG/SF/HA containing 50 mg HA cultured with rat BMMSCs enhanced cell adhesion, viability, the expression of all the osteogenesis-related markers in vitro and promoted superior calvarial defect repair in vivo, through modulating gene and protein expression levels [185].

Additionally, human MSCs seeded on regularly and randomly patterned photodegradable PEG hydrogel surfaces with different stiff-to-soft ratios from ~2–3 kPa to ~10–12 kPa displayed higher cell spread, elongated morphologies, and superior YAP activation and osteogenic differentiation on the regularly patterned regions, as compared to those cultured on random patterns [186]. High PEG substrate stiffness (~25 kPa) and α5β1 integrin signaling stimulated by c(RRETAWA) induced osteogenic differentiation of human MSCs [187].
