Temperature‐Induced Hydrogels Through Self‐Assembly of Cholesterol‐Substituted Star PEG‐b‐PLLA Copolymers: An Injectable Scaffold for Tissue Engineering

Abstract

Partially cholesterol‐substituted 8‐arm poly(ethylene glycol)‐block‐poly(L‐lactide) (8‐arm PEG‐b‐PLLA‐cholesterol) has been prepared as a novel star‐shaped, biodegradable copolymer derivative. The amphiphilic 8‐arm PEG‐b‐PLLA‐cholesterol aqueous solution (polymer concentration, above 3 wt%) exhibits instantaneous temperature‐induced gelation at 34 °C, but the virgin 8‐arm PEG‐b‐PLLA does not, irrespective of concentration. Moreover, an extracellular matrix (ECM)‐like micrometer‐scale network structure has been created with favorable porosity for three‐dimensional proliferation of cells inside the hydrogel. This network structure is mainly attributed to specific self‐assembly between cholesterol groups. The 10 and 20 wt% hydrogels are eroded gradually in phosphate buffered saline at 37 °C over the course of a month, and after that the gel becomes completely dissociated. Moreover, L929 cells encapsulated into the hydrogel are viable and proliferate three‐dimensionally inside the hydrogels. Thus, in‐vitro cell culture studies demonstrate that 8‐arm PEG‐b‐PLLA‐cholesterol is a promising candidate as a novel injectable cellular scaffold.

Injectable Biodegradable Hydrogels

“…[106] BSA was released from the wafers over the course of 30 days with an initial burst release. L929 cells encapsulated in cholesterol end-capped star PEG-PLLA hydrogels (10 and 20 wt.-%) were viable and proliferated in three dimensions within the hydrogels, [46] indicating that the polymer could be used as an injectable cellular scaffold. The PEG/PPG/PHB hydrogel is a promising candidate for the controlled release of protein.…”

“…PLGA Chondrocyte MPEG-PCL rBMSC, dexamethasone [104] FITC-BSA, BSA [105,106] Cholesterol end-capped star PEG-PLLA L929 cells [46] PEG/PPG/PHB BSA [48] Polyphosphazenes FITC-dextran, HSA [107] Doxorubicin, paclitaxel [108,112] FITC-albumin [109] Pancreatic islets, hepatocytes [110,111] C/GP Camptothecin, insulin [113,114] Bovine chondrocytes [115] pH/temperature-sensitive OSM-PCLA-PEG-PCLA-OSM Paclitaxel [116] hMSCs [117] PAE-PCL-PEG-PCL-PAE Insulin [82,118] (PCL-PEG-PCL-PAU) n Paclitaxel [86] (PEG-PAU) m Chlorambucil [87] PAA-PEG-PAA Flurbiprofen [90] PAE-PEG-PAE Lidocaine [89] matrices or cell growth depots. Table 1 summarizes the biomedical applications of the biodegradable injectable hydrogels.…”

“…Cholesterol endcapped star PEG-PLLA copolymers (above 3 wt.-%) in water also exhibited thermal gelation, but PEG-PLLA itself did not. [46] Gelation was induced by the strong hydrophobic association of the cholesterol group. Poly[(R)-3-hydroxybutyrate] (PHB) is a natural biodegradable polyester produced by bacteria.…”

Mixing a Sol and a Precipitate of Block Copolymers with Different Block Ratios Leads to an Injectable Hydrogel

“…Ohya and co-workers synthesized partially cholesterol-substituted 8-arm PEG-b-PLLA copolymers. 39 The main advantage of this injectable hydrogel is its high mechanical strength to act as a cellular scaffold. In our preceding researches, a surprising end-group effect on macroscopic physical gelation of PLGA-PEG-PLGA triblock copolymer aqueous solutions has been found, 40 which revealed that an end-capping approach could be employed to obtain novel thermosensitive hydrogels.…”

“…[35][36][37][38][39][40] Vermonden et al developed thermosensitive hydrogels based on poly(N-(2-hydroxypropyl) methacrylamide lactate)-b-poly(ethylene glycol)-b-poly(N-(2-hydroxypropyl) methacrylamide lactate) (PHPMAm lac -PEG-PHPMAm lac ) triblock copolymers. 36 The copolymers can become soluble in physiological conditions following the hydrolyzation of lactate groups which linked with the HPMAm monomers.…”