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

Advanced Functional Polymers for Unmet Medical Challenges

International audienceA significant part of medicine relies on biomaterials, which are designed to interact with biological tissues for therapeutic or diagnostic purposes. A number of major trends can be distinguished in the multidisciplinary field of biomaterials science, including the precise synthesis of biomaterial building blocks, elucidation of biomaterial processing–structure–property correlations, as well as clarification of the interactions between living tissues and biomaterials. Moreover, advances in biofabrication facilitate the development of tailored implants with improved functionality, whereas recent achievements in medical imaging allow for a detailed evaluation of the performance and spatiotemporal behavior of medical devices and nanomedicine formulations

Bio-based composite hydrogels for biomedical applications

International audienceHydrogels are three-dimensional, water-swollen polymer networks that have been widely studied for biomedical applications such as tissue engineering and the controlled delivery of biologically active agents. Since the pioneering work of Wichterle and Lim in the 1960s, hydrogel research has shifted from relatively simple single polymer networks to multifunctional composite hydrogels that better mimic the complex nature of living tissues. Bio-based polymers, which can be obtained from renewable natural resources, attract increasing attention for use in biomaterials in view of the recent demands for a reduction in the environmental impact of the polymer industry and the development of a sustainable society. Moreover, biobased polymers are often biodegradable and exhibit a significant level of biocompatibility and biomimicry, which are highly desired properties with regard to in vivo application. This review presents the state-of-the-art in the field of bio-based composite hydrogels for biomedical applications, thereby focusing on different types of polymeric components that have been combined with hydrogels to obtain materials with unique, synergistic properties: particles (including micelles and microspheres), electrospun fibres and nanocellulose. In addition, the challenges are described that should be overcome to facilitate clinical application of these versatile and environmentally responsible biomaterials

Hydrogels based on amphiphilic PEG star block copolymers

Hydrogels are hydrophilic polymer networks that are able to retain large amounts of water. They generally exhibit excellent biocompatibility and are accordingly of interest for biomedical and pharmaceutical applications such as systems for the controlled delivery of biologically active agents. Hydrogels are networks that can be physically crosslinked by non-covalent interactions and/or chemically crosslinked by covalent bonds. Both approaches have been used in recent years for the preparation of hydrogels that can be applied under physiological conditions. Of special interest are biodegradable injectable hydrogels, also called “in situ” forming hydrogels. These gels are formed at the injection site after the introduction of fluid precursors in a minimally invasive manner. “In situ” forming hydrogels offer several advantages over implantation of pre-shaped devices. There is no need for surgical procedures and their initially flowing nature ensures proper shape adaptation as well as a good fit with the surrounding tissue. Moreover, cells or biologically active agents can be easily incorporated in the injectable fluid.\ud Hydrogel based controlled drug delivery systems can potentially be used to address a number of issues that are encountered in conventional drug delivery, such as poor control of local or systemic drug concentration and the low solubility of many therapeutic agents in biological fluids. Most physically and chemically crosslinked biodegradable hydrogels that have been applied as controlled drug delivery systems are based on linear amphiphilic block copolymers of poly(ethylene glycol) (PEG) and aliphatic polyesters. Star block copolymers offer various advantages over linear polymers, such as increased solubility in aqueous media and a higher concentration of functional end groups. Starting from an 8-armed PEG block we designed and explored different block copolymers composed of outer poly(lactide) (PLA) or poly(trimethylene carbonate) (PTMC) blocks, for the preparation of physically or chemically crosslinked injectable hydrogels. The gelation and hydrogel degradation mechanisms involved were investigated in detail and their potential as systems for the controlled delivery of biologically active agents was evaluated

Pectin hydrogels, aerogels, cryogels and xerogels: Influence of drying on structural and release properties

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Tuning bio-aerogel properties for controlling drug delivery. Part 2: Cellulose-pectin composite aerogels

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Robust & thermosensitive poly(ethylene glycol)-poly(ε-caprolactone) star block copolymer hydrogels

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