Yixiao Dong

3D Single Cyclized Polymer Chain Structure from Controlled Polymerization of Multi-Vinyl Monomers: Beyond Flory–Stockmayer Theory

Controlled/living radical polymerization (CRP) is a widely used technique that allows the synthesis of defined polymer architectures through precise control of molecular weights and distributions. However, the architectures of polymers prepared by the CRP techniques are limited to linear, cross-linked, and branched/dendritic structures. Here, we report the preparation of a new 3D single cyclized polymer chain structure from an in situ deactivation enhanced atom transfer radical polymerization of multivinyl monomers (MVMs), which are conventionally used for the production of branched/cross-linked polymeric materials as defined by P. Flory and W. Stockmayer nearly 70 years ago. We provide new evidence to demonstrate that it is possible to kinetically control both the macromolecular architecture and the critical gelling point in the polymerization of MVMs, suggesting the classical Flory-Stockmayer mean field theory should be supplemented with a new kinetic theory based on the space and instantaneous growth boundary concept.

Performance of an in situ formed bioactive hydrogel dressing from a PEG-based hyperbranched multifunctional copolymer.

Hydrogel dressings have been widely used for wound management due to their ability to maintain a hydrated wound environment, restore the skins physical barrier and facilitate regular dressing replacement. However, the therapeutic functions of standard hydrogel dressings are restricted. In this study, an injectable hybrid hydrogel dressing system was prepared from a polyethylene glycol (PEG)-based thermoresponsive hyperbranched multiacrylate functional copolymer and thiol-modified hyaluronic acid in combination with adipose-derived stem cells (ADSCs). The cell viability, proliferation and metabolic activity of the encapsulated ADSCs were studied in vitro, and a rat dorsal full-thickness wound model was used to evaluate this bioactive hydrogel dressing in vivo. It was found that long-term cell viability could be achieved for both in vitro (21days) and in vivo (14days) studies. With ADSCs, this hydrogel system prevented wound contraction and enhanced angiogenesis, showing the potential of this system as a bioactive hydrogel dressing for wound healing.

A rapid crosslinking injectable hydrogel for stem cell delivery, from multifunctional hyperbranched polymers via RAFT homopolymerization of PEGDA

Stem cell therapies have attracted much attention for the last few decades in the field of regenerative medicine and tissue engineering. The 3-dimensional (3D) microenvironment surrounding the transplanted stem cells plays an essential role that influences the cell fate and behaviors. Thus advanced functional biomaterials and extracellular matrix (ECM) replacements with adjustable chemical, mechanical and bioactive properties are requisites in this field. In this study, PEG-based hyperbranched multifunctional homopolymers were developed via RAFT homopolymerization of the divinyl monomer of poly(ethylene glycol) diacrylate (PEGDA). Due to its high degree of multi-acrylate functionality, the hyperbranched polyPEGDA can rapidly crosslink with a thiolated hyaluronic acid under physiological conditions and form an injectable hydrogel for cell delivery. In addition, by simply varying the synthesis conditions such as the reaction time and the ratio of the monomer to the chain transfer agent (CTA), the polymer molecular weight, acrylate functionality degree and the cyclized/hyperbranched polymeric architecture can be finely controlled in a one-step reaction. The gelation speed and the mechanical properties of this hydrogel can be easily adjusted by altering the crosslinking conditions. Rat adipose-derived stem cells (rASCs) were embedded into the in situ crosslinked hydrogels, and their cellular behavior such as the morphology, viability, metabolic activity and proliferation were fully evaluated. The results suggested that the hydrogel maintained good cell viability and it can be easily modified with other bioactive signals, which provide this injectable hydrogel delivery system with good potential for polymeric biomaterials and tissue regeneration applications.

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.

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.

An in vitro approach for production of non-scar minicircle DNA vectors

Minicircle (MC) DNA vectors have shown prolonged expression in gene transfection studies. Here we have developed a facile approach based on enzyme-catalyzed reactions to produce the MC DNA in vitro. eGFP plasmid was inserted by two mirror-symmetry pairs of EcoRV and HindIII restriction enzyme sites at both sides of the expression cassette. The highly purified eGFP MC DNA vector was obtained through a dephosphorylating/re-exposing process, followed by a selective ligation of MC DNA and selective removal of the bacterial backbone fragment. The GFP expression study showed a significant improvement by using MC vectors. This method mimics the recombination process in vitro, avoids the need for specific bacterial strains, strict inducing strategy and complex purification approach, which provides potential for manufacturing the high-quality minicircle DNA vectors for vaccination and gene therapy applications.

Hydrolytically Degradable Hyperbranched PEG‐Polyester Adhesive with Low Swelling and Robust Mechanical Properties

Photocrosslinkable and water soluble hyperbranched PEG-polyester polymers (HPEGDA) have been developed as robust degradable adhesives. The HPEGDA polymers have been synthesized from controlled homopolymerization of poly(ethylene glycol) diacrylate (PEGDA700 ) via in situ deactivation enhanced atom transfer radical polymerization (DE-ATRP). By introducing a high initiator-to-monomer ratio, the obtained HPEGDA polymer is composed of extremely short carbon-carbon backbones interconnected together by the long PEG chains as well as pendent photocrosslinkable acrylate moieties. Due to the extremely short C-C backbone, the long PEG chains can therefore be seen as the main chain, thus, HPEGDA polymers behave more like polyester which is a category of polymers that contain the ester functional group in their main chain. Photo-cured HPEGDA can be readily adhered to tissue forming a patch with robust mechanical and adhesive strengths. The degradation profile by hydrolysis of polyester blocks as well as a significantly low swelling ratio of HPEGDA gels in an aqueous environment allow them to have great potential for sealing and repair of internal tissue. Furthermore, HPEGDA gels appear to have minor significant cytotoxicity in vitro. These unique properties indicate that the reported HPEGDA polymers are well poised for the development of adhesive tissue engineering matrixes, wound dressings, and sealants.

An acetal-based polymeric crosslinker with controlled pH-sensitivity

Even though collagen hydrogels have been used in many biomedical applications due to their unique characteristics, they lack in mechanical stability and resistance to enzymatic degradation. Aiming at the elimination of these drawbacks, collagen hydrogels have been crosslinked with a variety of synthetic crosslinkers all of which presented increased toxicity, which resulted in their limited use in biomedical devices. In order to overcome this limitation, a branched copolymer based on N-hydroxysuccinimide (NHS) activated poly(ethylene glycol) (PEG) groups was synthesized by in situ deactivation enhanced atom transfer radical polymerization (DE-ATRP) and used as crosslinker for collagen hydrogels. The NHS-PEG polymer was modified with labile acetal linkages (acetal-NHS) which made it responsive to pH-alterations and its responsiveness was studied at various pH. The activated acetal-NHS polymeric crosslinker demonstrated long-term stability at neutral pH but underwent hydrolysis at acidic pH, showing strongly pH-dependent degradation properties. By using the acetal-NHS polymeric crosslinker, collagen hydrogels with controlled degradation profiles were fabricated. Both the acetal-NHS crosslinker and the crosslinked collagen hydrogels exhibited excellent cytocompatibility.

PEG based hyperbranched polymeric hollow nanospheres

The synthesis of a new PEG based hyperbranched copolymer of poly(ethylene glycol) methyl ether methacrylate-co-ethylene glycol dimethacrylate (PEGMEMA-co-EGDMA) was achieved via a one-step in situ deactivation enhanced atom transfer radical polymerization (DE-ATRP). Then, hollow PEG based nanospheres were fabricated from this polymer using a solvent evaporation method and post-stabilisation strategy. Furthermore, the analysis using a cellular metabolic activity assay proved that the copolymer did not affect cellular metabolism, indicating that this PEG based polymeric nanosphere has potential for use in drug delivery applications.

Synthesis, characterisation and phase transition behaviour of temperature-responsive physically crosslinked poly (N-vinylcaprolactam) based polymers for biomedical applications

Poly (N-vinylcaprolactam) (PNVCL) is a polymer which offers superior characteristics for various potential medical device applications. In particular it offers unique thermoresponsive capabilities, which fulfils the material technology constraints required in targeted drug delivery applications. PNVCL phase transitions can be tailored in order to suit the requirements of current and next generation devices, by modifying the contents with regard to the material composition and aqueous polymer concentration. In this study, physically crosslinked Poly (N-vinylcaprolactam)-Vinyl acetate (PNVCL-VAc) copolymers were prepared by photopolymerisation. The structure of the polymers was established by Fourier transform infrared spectroscopy, nuclear magnetic resonance and gel permeation chromatography. The polymers were further characterised using differential scanning calorimetry and swelling studies. Determination of the LCST of the polymers in aqueous solution was achieved by employing four techniques; cloud point, UV-spectrometry, differential scanning calorimetry and rheometry. Sol-gel transition was established using tube inversion method and rheological analysis. This study was conducted to determine the characteristics of PNVCL with the addition of VAc, and to establish the effects on the phase transition. The PNVCL based polymers exhibited a decrease in the LCST as the composition of VAc increased. Sol-gel transition could be controlled by altering the monomeric feed ratio and polymer concentration in aqueous milieu. Importantly all copolymers (10wt% in solution) underwent gelation between 33.6 and 35.9°C, and based on this and the other materials properties recorded in this study, these novel copolymers have potential for use as injectable in situ forming drug delivery systems for targeted drug delivery.