Hongyun Tai

A highly effective gene delivery vector – hyperbranched poly(2-(dimethylamino)ethyl methacrylate) from in situ deactivation enhanced ATRP

A hyperbranched 2-(dimethylamino)ethyl methacrylate (DMAEMA) based polymer has been synthesised by a one-pot in situ deactivation enhanced atom transfer radical polymerisation (DE-ATRP); it exhibits much higher transfection ability than linear poly(DMAEMA) and is comparable to the well known branched poly(ethylene imine) (PEI) and the SuperFect dendrimer but with lower cytotoxicity.

Thermoresponsive and Photocrosslinkable PEGMEMA-PPGMA-EGDMA Copolymers from a One-Step ATRP Synthesis

Thermoresponsive and photocrosslinkable polymers can be used as injectable scaffolds in tissue engineering to yield gels in situ with enhanced mechanical properties and stability. They allow easy handling and hold their shapes prior to photopolymerization for clinical practice. Here we report a novel copolymer with both thermoresponsive and photocrosslinkable properties via a facile one-step deactivation enhanced atom transfer radical polymerization (ATRP) using poly(ethylene glycol) methyl ether methylacrylate (PEGMEMA, M(n) = 475) and poly(propylene glycol) methacrylate (PPGMA, M(n) = 375) as monofunctional vinyl monomers and up to 30% of ethylene glycol dimethacrylate (EGDMA) as multifunctional vinyl monomer. The resultant PEGMEMA-PPGMA-EGDMA copolymers have been characterized by gel permeation chromatography (GPC) and 1H NMR analysis, which demonstrate their multivinyl functionality and hyperbranched structures. These water-soluble copolymers show lower critical solution temperature (LCST) behavior at 32 degrees C, which is comparable to poly(N-isopropylacrylamide) (PNIPAM). The copolymers can also be cross-linked by photopolymerization through their multivinyl functional groups. Rheological studies clearly demonstrate that the photocrosslinked gels formed at a temperature above the LCST have higher storage moduli than those prepared at a temperature below the LCST. Moreover, the cross-linking density of the gels can be tuned to tailor their porous structures and mechanical properties by adjusting the composition and concentration of the copolymers. Hydrogels with a broad range of storage moduli from 10 to 400 kPa have been produced.

Putting the fizz into chemistry: applications of supercritical carbon dioxide in tissue engineering, drug delivery and synthesis of novel block copolymers.

This paper describes the recent progress at Nottingham towards the exploitation of the unique properties of scCO(2) (supercritical carbon dioxide) for the preparation of polymeric scaffolds for tissue engineering applications and new devices for controlled drug delivery, as well as the synthesis of novel block copolymers by the combination of eROP (enzymatic ring opening polymerization) and controlled polymerization methods for the potential use as drug carriers.

Photo-Cross-Linked Hydrogels from Thermoresponsive PEGMEMA-PPGMA-EGDMA Copolymers Containing Multiple Methacrylate Groups: Mechanical Property, Swelling, Protein Release, and Cytotoxicity

Photo-cross-linked hydrogels from thermoresponsive polymers can be used as advanced injectable biomaterials via a combination of physical interaction (in situ thermal gelation) and covalent cross-links (in situ photopolymerization). This can lead to gels with significantly enhanced mechanical properties compared to non-photo-cross-linked thermoresponsive hydrogels. Moreover, the thermally phase-separated gels have attractive advantages over non-thermoresponsive gels because thermal gelation upon injection allows easy handling and holds the shape of the gels prior to photopolymerization. In this study, water-soluble thermoresponsive copolymers containing multiple methacrylate groups were synthesized via one-step deactivation enhanced atom transfer radical polymerization (ATRP) of poly(ethylene glycol) methyl ether methacrylate (PEGMEMA, M(n) = 475), poly(propylene glycol) methacrylate (PPGMA, M(n) = 375), and ethylene glycol dimethacrylate (EGDMA) and were used to form covalent cross-linked hydrogels by photopolymerization. The cross-linking density was found to have a significant influence on the mechanical and swelling properties of the photo-cross-linked gels. Release studies using lysozyme as a model protein demonstrated a sustained release profile that varied dependent on the copolymer composition, cross-linking density, and the temperature. Mouse C2C12 myoblast cells were cultured in the presence of the copolymers at concentrations up to 1 mg/mL. It was found that the majority of the cells remained viable, as assessed by Alamar Blue, lactate dehydrogenase (LDH), and Live/Dead cell viability/cytotoxicity assays. These studies demonstrate that thermoresponsive PEGMEMA-PPGMA-EGDMA copolymers offer potential as in situ photopolymerizable materials for tissue engineering and drug delivery applications through a combination of facile synthesis, enhanced mechanical properties, tunable cross-linking density, low cytotoxicity, and accessible functionality for further structure modifications.

The effect of processing variables on morphological and mechanical properties of supercritical CO2 foamed scaffolds for tissue engineering.

The porous structure of a scaffold determines the ability of bone to regenerate within this environment. In situations where the scaffold is required to provide mechanical function, balance must be achieved between optimizing porosity and maximizing mechanical strength. Supercritical CO(2) foaming can produce open-cell, interconnected structures in a low-temperature, solvent-free process. In this work, we report on foams of varying structural and mechanical properties fabricated from different molecular weights of poly(DL-lactic acid) P(DL)LA (57, 25 and 15 kDa) and by varying the depressurization rate. Rapid depressurization rates produced scaffolds with homogeneous pore distributions and some closed pores. Decreasing the depressurization rate produced scaffolds with wider pore size distributions and larger, more interconnected pores. In compressive testing, scaffolds produced from 57 kDa P(DL)LA exhibited typical stress-strain curves for elastomeric open-cell foams whereas scaffolds fabricated from 25 and 15 kDa P(DL)LA behaved as brittle foams. The structural and mechanical properties of scaffolds produced from 57 kDa P(DL)LA by scCO(2) ensure that these scaffolds are suitable for potential applications in bone tissue engineering.

Image-based characterization of foamed polymeric tissue scaffolds

Tissue scaffolds are integral to many regenerative medicine therapies, providing suitable environments for tissue regeneration. In order to assess their suitability, methods to routinely and reproducibly characterize scaffolds are needed. Scaffold structures are typically complex, and thus their characterization is far from trivial. The work presented in this paper is centred on the application of the principles of scaffold characterization outlined in guidelines developed by ASTM International. Specifically, this work demonstrates the capabilities of different imaging modalities and analysis techniques used to characterize scaffolds fabricated from poly(lactic-co-glycolic acid) using supercritical carbon dioxide. Three structurally different scaffolds were used. The scaffolds were imaged using: scanning electron microscopy, micro x-ray computed tomography, magnetic resonance imaging and terahertz pulsed imaging. In each case two-dimensional images were obtained from which scaffold properties were determined using image processing. The findings of this work highlight how the chosen imaging modality and image-processing technique can influence the results of scaffold characterization. It is concluded that in order to obtain useful results from image-based scaffold characterization, an imaging methodology providing sufficient contrast and resolution must be used along with robust image segmentation methods to allow intercomparison of results.

In situ formed hybrid hydrogels from PEG based multifunctional hyperbranched copolymers: a RAFT approach

Polyethylene glycol (PEG) based multifunctional hyperbranched copolymers with a high degree of vinyl functional groups were developed using RAFT polymerisation. This platform technology allowed the development of in situ crosslinkable hybrid injectable hydrogels via “click” type reactions for the delivery of human adipose derived stem cells.

A fluorescently labeled, hyperbranched polymer synthesized from DE-ATRP for the detection of DNA hybridization

The early detection of oligonucleotide biomarkers of disease, such as microRNAs, has been established as a fundamental factor in cancer diagnosis. As the levels of these small molecules (microRNAs) in blood have recently been found to be significantly affected in cancer patients, they offer a means of early stage detection of cancer. Towards the goal of creating a novel method of DNA hybridization detection, we report the detection of specific sequences of small oligonucleotides in a model experiment carried out in serum. The results shown here display the versatility of the DE-ATRP method in synthesizing a specific polymer structure capable of changing its physical properties in the presence of double stranded DNA. The polymer was labeled and used to detect single-stranded DNA in serum successfully.

Water soluble hyperbranched polymers from controlled radical homopolymerization of PEG diacrylate

A series of water soluble PEG based hyperbranched polymers were successfully synthesized by homopolymerization of poly(ethylene glycol) diacrylate (PEGDA) (Mn = 575 and 700 g mol−1 respectively) via vinyl oligomer combination. The homopolymerization of diacrylate macromers underwent a slow vinyl propagation combined with a polycondensation by coupling of reactive oligomers. At a high initiator-to-monomer ratio (e.g. 1 : 2), high monomer conversions up to 96% were achieved in concentrated reaction conditions (60% w/v) without gelation. The hyperbranched polymers obtained from homopolymerization of PEGDA575 show concentration-dependent thermoresponsive properties in aqueous solutions.

Can Flory-Stockmayer theory be applied to predict conventional free radical polymerization of multivinyl monomers? A study via Monte Carlo simulations

The conventional free radical polymerization (FRP) of multivinyl monomers (MVMs) inevitably leads to gelation even at low monomer conversion resulting in difficulties to control and monitor the reaction process. Flory and Stockmayer (F-S theory) studied it based on two fundamental assumptions: (1) independent and equivalent vinyl groups; (2) no intramolecular cyclization. However, until now its applicability to FRP of MVMs (especially regarding the extent of intramolecular cyclization) is still controversial. In this paper, Monte Carlo simulations are used to study FRP of divinyl monomers by two kinetic models: with/without cyclization models. The results of the simulations are compared with the calculated gel points based on F-S theory and the experimental data. It is found that the intramolecular cyclization has a negligible impact on the polymerization process and the gel point before gelation, which are in agreement with the prediction by F-S theory, but the effect becomes significant above the gel points.