Synthesis, characterization and application of reversible PDLLA-PEG-PDLLA copolymer thermogels in vitro and in vivo

Abstract

In this study, a series of injectable thermoreversible and thermogelling PDLLA-PEG-PDLLA copolymers were developed and a systematic evaluation of the thermogelling system both in vitro and in vivo was performed. The aqueous PDLLA-PEG-PDLLA solutions above a critical gel concentration could transform into hydrogel spontaneously within 2 minutes around the body temperature in vitro or in vivo. Modulating the molecular weight, block length and polymer concentration could adjust the sol-gel transition behavior and the mechanical properties of the hydrogels. The gelation was thermally reversible due to the physical interaction of copolymer micelles and no crystallization formed during the gelation. Little cytotoxicity and hemolysis of this polymer was found, and the inflammatory response after injecting the hydrogel to small-animal was acceptable. In vitro and in vivo degradation experiments illustrated that the physical hydrogel could retain its integrity as long as several weeks and eventually be degraded by hydrolysis. A rat model of sidewall defect-bowel abrasion was employed, and a significant reduction of post-operative adhesion has been found in the group of PDLLA-PEG-PDLLA hydrogel-treated, compared with untreated control group and commercial hyaluronic acid (HA) anti-adhesion hydrogel group. As such, this PDLLA-PEG-PDLLA hydrogel might be a promising candidate of injectable biomaterial for medical applications.

Black‐Phosphorus‐Incorporated Hydrogel as a Sprayable and Biodegradable Photothermal Platform for Postsurgical Treatment of Cancer

“…Typically, the aqueous polymer solutions at room temperature or below can spontaneously turn into nonflowing gels in response to the physiological temperature. Here, PLEL, a typical biodegradable and biocompatible temperature‐sensitive hydrogel,47, 48 is selected as the agent to load the BP nanosheets. As shown in Figure 2 a, the polymeric chains of PLEL can self‐assemble into core–shell like micelles in the aqueous solution.…”

“…Multimodes emerge during degradation (see the red dashed rectangle in Figure 4c) possibly due to degradation products with small molecular weights. According to previous studies,47 degradation of PLEL hydrogels is proceeded by steady hydrolysis of the ester linkage into segments (reduced molecular weight), oligomers and monomers, and finally dissociation to carbon dioxide and water. The BP@PLEL hydrogel with reasonable biodegradability not only provides excellent wound‐healing performance, but also enables clearance of the BP@PLEL hydrogel after fulfilling the therapeutic functions.…”

“…Moreover, BP nanosheets degrade naturally in the physiological environment forming harmless PO 4 3− as the final degradation product 44, 45, 46. Here, by combining BP with PLEL which is a biodegradable and biocompatible thermosensitive hydrogel,47, 48 the BP@PLEL is photothermally responsive to NIR irradiation and the cross‐linked gel structure is formed as the temperature is increased. In vitro and in vivo experiments are performed to investigate the biodegradability and biocompatibility of the BP@PLEL hydrogel and a PTT postoperative treatment strategy is described to prevent the recurrence of cancer.…”

Development of hydrogels for regenerative engineering

“…The most commonly used natural hydrogel materials include: collagen, hyaluronic acid, gelatin, chitosan, alginate, and chondroitin sulfate . On the other hand, synthetic biodegradable polymers with controlled microstructures and mechanical properties have also been widely utilized for the fabrication of hydrogels, including: poly(ethylene glycol) (PEG), poly( N ‐isopropylacrylamide) (PNIPAm), poly(glycolic acid) (PGA), and poly(lactic‐co‐glycolic) acid (PLGA) . However, due to the limited biological moieties of synthetic hydrogels, various combinations of natural and synthetic hydrogels have been developed with enhanced biological and mechanical properties, such as chitosan‐PEG, collagen‐PNIPAm, and chitosan‐poly(vinyl alcohol) (PVA) .…”

“…The most commonly used natural hydrogel materials include: collagen, hyaluronic acid, gelatin, chitosan, alginate, and chondroitin sulfate [12]. On the other hand, synthetic biodegradable polymers with controlled microstructures and mechanical properties have also been widely utilized for the fabrication of hydrogels, including: poly(ethylene glycol) (PEG), poly(N-isopropylacrylamide) (PNIPAm), poly(glycolic acid) (PGA), and poly(lactic-co-glycolic) acid (PLGA) [13][14][15]. However, due to the limited biological moieties of synthetic hydrogels, various combinations of natural and synthetic hydrogels have been developed with enhanced N-hydroxysuccinimide; PCL, polycaprolactone; PDGF-BB, platelet-derived growth factor-BB; PEG, polyethylene glycol; PEGDA, PEG-diacrylate; PGA, poly(glycolic acid); PLGA, poly(L-glutamic acid); PNIPAm, poly(N-isopropylacrylamide); PVA, polyvinyl alcohol; QL6, K 2 (QL) 6 K 2 ; RGD, arginyl-glycylaspartic acid; ROS, reactive oxygen species; SAPs, self-assembling peptides; SEM, scanning electron microscope; TCP, tricalcium phosphate; TGF-β, transforming growth factor-β; UV, ultraviolet; VEGF, vascular endothelial growth factor biological and mechanical properties, such as chitosan-PEG, collagen-PNIPAm, and chitosan-poly(vinyl alcohol) (PVA) [16][17][18][19].…”