In situ forming stereocomplexed and post-photocrosslinked acrylated star poly(ethylene glycol)-poly(lactide) hydrogels

Biodegradable acrylate end-group functionalized poly(ethylene glycol)-poly(lactide) (PEG-PLA) star block copolymer hydrogels were formed by the consecutive physical gelation through stereocomplexation of star shaped PEG-(PLLA)8 and PEG-(PDLA)8 enantiomers and UV photopolymerization. The 8-armed PEG-PLA star block copolymers were prepared by ring opening polymerization of lactide onto an amine end-group functionalized PEG with a molecular weight of 20 kg/mol using stannous octoate as a catalyst. The degree of polymerization of the PLA blocks was 12 lactyl units and the end hydroxyl groups were reacted with acryloyl chloride to give the required acrylate end groups. Aqueous solutions of enantiomeric mixtures of the PEG-(PLA)8 macromonomers formed physically crosslinked hydrogels above a critical gel concentration of 4 w/v%. Subsequent photopolymerization at 365 nm in the presence of Irgacure 2959 resulted in gels with improved mechanical properties and hydrolytic stability. With 40% polymer mass loss after 45 d in vitro, these hydrogels show excellent resistance against hydrolytic degradation and dissolution, which is believed to result from the combination of stable amide linkages between the PEG and PLA blocks and the high physical and chemical crosslink density owing to the star architecture

Solid-state NMR study of stereocomplexes formed by enantiomeric star-shaped PEG-PLA copolymers in water

Solid-state NMR was applied to samples obtained by freeze-drying hydrogels of 1:1 (PEG65-NHCO-PLLA13)8/(PEG65-NHCO-PDLA13)8 or (PEG65-NHCO-PDLA13)8 only star block copolymers (where PEG, PLLA, and PDLA stand for poly(ethylene glycol), poly(l-lactide), and poly(d-lactide), respectively) in order to get insight into the different structural and dynamic properties of stereocomplexed poly(lactide) (PLA) aggregates with respect to single enantiomer ones responsible for the improved mechanical and degradation properties of the corresponding hydrogels. 13C MAS NMR experiments together with 13C relaxation time measurements indicated that the PLA domains in (PEG65-NHCO-PLLA13)8/(PEG65-NHCO-PDLA13)8 were highly crystalline, whereas those in (PEG65-NHCO-PDLA13)8 were mainly amorphous. On the basis of 1H relaxation and spin-diffusion experiments, similar average dimensions were determined for the PLA aggregates in the two samples. PLA stereocomplexation was found to strongly affect the conformational behavior of PEG chains. Under the assumption that freeze-drying preserves the structure of at least the PLA aggregates, the results obtained are of value for understanding self-aggregation of PEG–PLA star block copolymers in water

Self-assembly and photo-cross-linking of eight-armed PEG-PTMC star block copolymers

Eight-armed poly(ethylene glycol)-poly(trimethylene carbonate) star block copolymers (PEG-(PTMC)8) linked by a carbamate group between the PEG core and the PTMC blocks were synthesized by the metal-free, HCl-catalyzed ring-opening polymerization of trimethylene carbonate using an amine-terminated eight-armed star PEG in dichloromethane. Although dye solubilization experiments, nuclear magnetic resonance spectroscopy, and dynamic light scattering clearly indicated the presence of aggregates in aqueous dispersions of the copolymers, no physical gelation was observed up to high concentrations. PEG-(PTMC9)8 was end-group-functionalized using acryloyl chloride and photopolymerized in the presence of Irgacure 2959. When dilute aqueous dispersions of PEG-(PTMC9)8-Acr were UV irradiated, chemically cross-linked PEG-PTMC nanoparticles were obtained, whereas irradiation of more concentrated PEG-(PTMC9)8-Acr dispersions resulted in the formation of photo-cross-linked hydrogels. Their good mechanical properties and high stability against hydrolytic degradation make photo-cross-linked PEG-PTMC hydrogels interesting for biomedical applications such as matrices for tissue engineering and controlled drug delivery systems

Hydrogels for Therapeutic Delivery : Current Developments and Future Directions

Hydrogels are attractive materials for the controlled release of therapeutics because of their capacity to embed biologically active agents in their water-swollen network. Recent advances in organic and polymer chemistry, bioengineering and nanotechnology have resulted in several new developments in the field of hydrogels for therapeutic delivery. In this Perspective, we present our view on the state-of-the-art in the field, thereby focusing on a number of exciting topics, including bioorthogonal cross-linking methods, multicomponent hydrogels, stimuli-responsive hydrogels, nanogels, and the release of therapeutics from 3D printed hydrogels. We also describe the challenges that should be overcome to facilitate translation from academia to the clinic and last, we share our ideas about the future of this rapidly evolving area of research

Hydrogels for Therapeutic Delivery : Current Developments and Future Directions

Hydrogels are attractive materials for the controlled release of therapeutics because of their capacity to embed biologically active agents in their water-swollen network. Recent advances in organic and polymer chemistry, bioengineering and nanotechnology have resulted in several new developments in the field of hydrogels for therapeutic delivery. In this Perspective, we present our view on the state-of-the-art in the field, thereby focusing on a number of exciting topics, including bioorthogonal cross-linking methods, multicomponent hydrogels, stimuli-responsive hydrogels, nanogels, and the release of therapeutics from 3D printed hydrogels. We also describe the challenges that should be overcome to facilitate translation from academia to the clinic and last, we share our ideas about the future of this rapidly evolving area of research

Influence of amide versus ester linkages on the properties of eight-armed PEG-PLA star block copolymer hydrogels

Water-soluble eight-armed poly(ethylene glycol)-poly(l-lactide) star block copolymers linked by an amide or ester group between the PEG core and the PLA blocks (PEG-(NHCO)-(PLA)8 and PEG-(OCO)-(PLA)8) were synthesized by the stannous octoate catalyzed ring-opening polymerization of l-lactide using an amine- or hydroxyl-terminated eight-armed star PEG. At concentrations above the critical gel concentration, thermosensitive hydrogels were obtained, showing a reversible single gel-to-sol transition. At similar composition PEG-(NHCO)-(PLA)8 hydrogels were formed at significantly lower polymer concentrations and had higher storage moduli. Whereas the hydrolytic degradation/dissolution of the PEG-(OCO)-(PLA)8 takes place by preferential hydrolysis of the ester bond between the PEG and PLA block, the PEG-(NHCO)-(PLA)8 hydrogels degrade through hydrolysis of ester bonds in the PLA main chain. Because of their relatively good mechanical properties and slow degradation in vitro, PEG-(NHCO)-(PLA)8 hydrogels are interesting materials for biomedical applications such as controlled drug delivery systems and matrices for tissue engineering

Self-Aggregation of Gel Forming PEG-PLA Star Block Copolymers in Water

The aggregation behavior and dynamics of poly(ethylene glycol) (PEG) and poly(lactide) (PLA) chains in a homologous series of eight-armed PEG-PLA star block copolymers ((PEG65-NHCO-PLAn)8 with n = 11, 13, and 15) in water at different concentrations and temperatures were studied by means of 1H and 13C NMR spectroscopy and 1H longitudinal relaxation time analysis. The state of water in these systems was also investigated through the combined use of 1H and 2H longitudinal relaxation time measurement. On the basis of the NMR experimental findings and of dynamic light scattering measurements, (PEG65-NHCO-PLAn)8 in water can be described as self-aggregated systems with quite rigid hydrophobic domains made of PLA chains and aqueous domains where both PEG chains and water molecules undergo fast dynamics. A smaller number of rigid domains was found for (PEG65-NHCO-PLA11)8 with respect to the homologous copolymers with longer PLA chains. At low concentrations, the PLA domains are mainly formed by chains belonging to the same molecule, thus giving rise to unimolecular micelles. At intermediate concentrations, that is, above the critical association concentration (CAC) but below the critical gel concentration (CGC), nanogels are formed by interconnection of several PLA domains through shared unimers. Above the CGC, the network is extended to the entire system, giving rise to macroscopic gels. In all cases, a fraction of PLA chains remains quite mobile and exposed to water due to topological constraints of the star architecture