Thermosensitive block copolymer hydrogels based on poly(ɛ‐caprolactone) and polyethylene glycol for biomedical applications: State of the art and future perspectives

Abstract

This review focuses on the challenges associated with the design and development of injectable hydrogels of synthetic origin based on FDA approved blocks, such as polyethylene glycol (PEG) and poly(ɛ-caprolactone) (PCL). An overview of recent studies on inverse thermosensitive PEG/PCL hydrogels is provided. These systems have been proposed to overcome the limitations of previously introduced degradable thermosensitive hydrogels [e.g., PEG/poly(lactide-co-glycolic acid) hydrogels]. PEG/PCL hydrogels are advantageous due to their higher gel strength, slower degradation rate and availability in powder form. Particularly, triblock PEG/PCL copolymers have been widely investigated, with PCL-PEG-PCL (PCEC) hydrogels showing superior gel strength and slower degradation kinetics than PEG-PCL-PEG (PECE) hydrogels. Compared to triblock PEG/PCL copolymers, concentrated solutions of multiblock PEG/PCL copolymers were stable due to their slower crystallization rate. However, the resulting hydrogel gel strength was low. Inverse thermosensitive triblock PEG/PCL hydrogels have been mainly applied in tissue engineering, to decrease tissue adherence or, in combination with bioactive molecules, to promote tissue regeneration. They have also found application as in situ drug delivery carriers. On the other hand, the wide potentialities of multiblock PEG/PCL hydrogels, associated with the stability of their water-based solutions under storage, their higher degradation time compared to triblock copolymer hydrogels and the possibility to insert bioactive building blocks along the copolymer chains, have not been fully exploited yet. A critical discussion is provided to highlight advantages and limitations of currently developed themosensitive PEG/PCL hydrogels, suggesting future strategies for the realization of PEG/PCL-based copolymers with improved performance in the different application fields.

Advancing biomaterials of human origin for tissue engineering

“…Due to its exceptional qualities, such as its biocompatibility, low immunogenicity, hydrolysis under physiological conditions, and FDA approval for clinical use, poly( ε -caprolactone) (PCL) is another synthetic polyester based on hydroxyalkanoic acids that has attracted intense attention in tissue engineering. This polymer is used either alone, as hydrophobic PCL, or as a PCL-containing amphiphilic block copolymer when in combination with other agents, resulting in improved performance in certain applications [70,79,80]. …”

The rheological anomaly in water-silicate systems: a possible thermodynamic explanation

“…In Table 1 It should be noted that despite the lack of a sufficiently reliable theoretical explanation of the effect in any system that demonstrates it, the phenomenon itself has become practical, in particular, in ceramic production when casting ceramic gels with methylcellulose as a thickener [12][13][14], as well as in medicine [15].…”

In Vivo Osteogenic Differentiation of Human Dental Pulp Stem Cells Embedded in an Injectable In Vivo‐Forming Hydrogel

“…[ 19 ] PC was synthesized via the polymerization of CL (7.8 g, 68.4 mmol) using MPEG ( M n , 750 g mol −1 ) (2.25 g, 3 mmol) as an initiator in the presence of 1.0 m solution of HCl in diethyl ether (6 mL, 6 mmol) at 25 °C. After 24 h, the reaction mixture was poured into hexane to precipitate a polymer that was separated from the supernatant by decantation.…”

“…PC aqueous solutions are fluid at room temperature and convert into in vivo hydrogels after subcutaneous injection. [18,19] Importantly, PC was sterilizable to prevent infection, easy to handle, and maintain adequate mechanical properties for the intended period.…”