The current limitations of calcium phosphate cements (CPCs) used in the field of bone regeneration consist of their brittleness, low injectability, disintegration in body fluids and low biodegradability. Moreover, no method is currently available to measure the setting time of CPCs in correlation with the evolution of the setting reaction. The study proposes that it is possible to improve and tune the properties of CPCs via the addition of a thermosensitive, biodegradable, thixotropic copolymer based on poly(lactic acid), poly(glycolic acid) and poly(ethylene glycol) (PLGA–PEG–PLGA) which undergoes gelation under physiological conditions. The setting times of alpha-tricalcium phosphate (α-TCP) mixed with aqueous solutions of PLGA–PEG–PLGA determined by means of time-sweep curves revealed a lag phase during the dissolution of the α-TCP particles. The magnitude of the storage modulus at lag phase depends on the liquid to powder ratio, the copolymer concentration and temperature. A sharp increase in the storage modulus was observed at the time of the precipitation of calcium deficient hydroxyapatite (CDHA) crystals, representing the loss of paste workability. The PLGA–PEG–PLGA copolymer demonstrates the desired pseudoplastic rheological behaviour with a small decrease in shear stress and the rapid recovery of the viscous state once the shear is removed, thus preventing CPC phase separation and providing good cohesion. Preliminary cytocompatibility tests performed on human mesenchymal stem cells proved the suitability of the novel copolymer/α-TCP for the purposes of mini-invasive surgery.

This paper deals with the influence of an incubation medium pH on the hydrolytic degradation of a novel thermosensitive biodegradable triblock copolymer based on hydrophilic poly(ethylene glycol) and hydrophobic copolymer poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA), consequently modified at α,ω-ends with itaconic acid (ITA) resulting in α,ω-itaconyl(PLGA-PEG-PLGA). Itaconic acid, obtained from renewable resources, delivers a reactive double bond and carboxylic functional group to the end of PLGA-PEG-PLGA copolymer: this is important for a reaction with biologically active substances. The suitability of the sample degradation was assessed depending on whether the copolymer formed a gel at 37 °C. Two reversible physical sol-gel-sol transitions from a sol (liquid phase) to a gel (solid phase) and back to a sol (suspension) were verified using the tube inverting method. The hydrolytical degradation was evaluated at a physiological temperature (37 °C) in the presence of phosphate solutions, at a pH of either 4.2 or 7.4 by monitoring the decrease of the number average molecular weight of copolymers by GPC. Moreover, the degradation kinetics was confirmed by the HPLC/DAD method, where the increasing amount of final degradation products (lactic and glycolic acids) was detected. The study demonstrated that the carboxylic groups modified copolymer (ITA/PLGA–PEG– PLGA/ITA) is more susceptible to hydrolytical degradation than the unmodified copolymer within first days of degradation at pH 7.4

Biodegradable amphiphilic PLGA–PEG–PLGA triblock copolymers end-terminated with itaconic acid (ITA) having reactive double bonds were synthesized by ring opening polymerization. The prepared α,ω-itaconyl-PLGA–PEG–PLGA telechelic macromonomers were additionally covalently crosslinked under an inert atmosphere by blue light irradiation without the use of a further cross-linker resulting in end-linked polymeric networks. The effects of the ITA amount attached to the α,ω-itaconyl-PLGA–PEG–PLGA copolymers and the crosslinking time on swelling behaviours and hydrolytic stability of the prepared well-defined polymeric network were investigated. Physicochemical properties were characterized by proton and carbon nuclear magnetic resonance spectroscopy (¹H NMR, ¹³C NMR), proton nuclear magnetic resonance relaxometry, attenuated total reflectance Fourier transformed infrared spectroscopy (ATR-FTIR) and thermogravimetric analysis (TGA). It was found that the hydrolytic stability of ITA modified PLGA–PEG–PLGA end-linked hydrogels enhances with both increasing the time of crosslinking and the amount of double bonds attached to α,ω-itaconyl-PLGA–PEG–PLGA polymer chains. In comparison with the original un-crosslinked α,ω-itaconyl-PLGA–PEG–PLGA copolymer, the hydrolytic stability of the end-linked hydrogels significantly increased. Three kinds of water fractions (unbound, weakly and strongly bonded) were determined by proton NMR relaxometry in hydrogels containing 63 mol% of ITA crosslinked for 40 minutes. Even for hydrogels surviving 32 days in water the NMR relaxometry showed structural collapse of the hydrogel probably due to breaking of end-linked nodes followed by hydrolysis faster than water diffusion after day 15 of immersion. End-linked α,ω-itaconyl-PLGA–PEG–PLGA hydrogels can be used in medical, biological or tissue engineering applications.