Tianyu Zhao

Mussel-inspired hyperbranched poly(amino ester) polymer as strong wet tissue adhesive

Current medical adhesives based on cyanoacrylates typically exhibit cellular toxicity. In contrast, fibrin adhesives are non-toxic but have poor adhesive properties. To overcome these drawbacks we designed a simple and scalable adhesive precursor inspired by marine mussel adhesion that functioned with strong adhesion in wet conditions and with low cytotoxicity. Dopamine, an-amine derivative of an amino acid abundantly present in mussel adhesive proteins, was co-polymerised with a tri-functional vinyl monomer, to form a hyperbranched poly(β-amino ester) polymer termed poly(dopamine-co-acrylate) (PDA). A variety of molecular weights and crosslinking methods were analysed using an ex vivo porcine skin model and an almost 4 fold increase in wet adhesion strength was observed compared to TISSEEL(®) fibrin sealant. With a fast curing time, degradable properties and low cytotoxicity, PDA is highly attractive for medical purposes and could have a broad impact on surgeries where surgical tissue adhesives, sealants, and haemostatic agents are used.

A biomimetic hyperbranched poly(amino ester)-based nanocomposite as a tunable bone adhesive for sternal closure

A novel mussel-inspired adhesive can bond well to the surface of wet bone and be programmed to set in a suitable manner for sternal closure applications. With good wet adhesion properties, low exothermic properties, biodegradability and low toxicity, we believe that this technology, which can be further built upon and modified, will endow intriguing potential for sternal closure.

On-demand and negative-thermo-swelling tissue adhesive based on highly branched ambivalent PEG–catechol copolymers

A series of well-designed highly branched PEG-catechol based thermo-responsive copolymers were synthesized via a one-pot RAFT polymerization. A varying degree of photocrosslinkable (meth)acrylate moieties were incorporated within the 3D structure to allow on-demand photocuring (strong cohesion, unlike conventional PEG adhesives). At the same time, multitudes of free catechol groups inspired from adhesive proteins of marine mussels were also introduced in the hyperbranched structure, giving rise to adherence to skin and cardiac tissue. The resulting ambivalent PEG-catechol based copolymers were systematically studied to investigate the effects of polymer composition on tissue bioadhesive and swelling properties, comparing acrylates to methacrylates and PEG to 2-hydroxyethyl acrylamide (HEAA). It was proved that DOPA played a major role in the adhesion performance as it significantly enhanced the adhesion performances on varied substrates. The highly branched PEG-catechol copolymers demonstrate the great potential in the design of novel surgical glues, sealants or drug delivery vectors.

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.

Main-chain degradable single-chain cyclized polymers as gene delivery vectors

Single-chain technology (SCT) allows the manipulation of polymeric architectures at an individual polymer chain level, providing a new platform for the fabrication of nanoscale polymeric objects. However, it remains problematic to apply this newborn technology to the biological and medical fields, since synthesis of single-chain polymeric nanoparticles relies heavily on controlled/living radical polymerization of vinyl based monomers, yielding a persistent non-degradable carbon-carbon based backbone. Moreover, the ultrahigh dilution conditions often required for single-chain polymer nanoparticle synthesis limits large-scale applicability. A versatile approach to achieve backbone degradability in single-chain cyclized polymers was developed by combining ring-opening addition polymerization and intramolecular cyclization into a one-pot RAFT copolymerization of cyclic and mono/multi-vinyl monomers system under concentrated conditions. The in situ intramolecular cyclization of individual propagating chains was achieved by kinetic control and statistical manipulation of mono- and multi-vinyl monomer copolymerization. The cyclic allylsulfide monomer 3-methylidene-1,9-dioxa-5,12,13-trithiacyclopentadecane-2,8-dione (MDTD) was copolymerized via the ring-opening pathway to introduce disulfide groups into the vinyl-based backbone without compromising the single chain propagation nature. Backbone degradable single chain polymeric nanoparticles were obtained with molecular weights of 10kDa and MDTD incorporation ratios of 4.7%. Chemical degradation of the nanoparticles confirmed both their single chain nature, as well as backbone degradability. The single-chain cyclized polymeric nanoparticles were evaluated for their gene transfection capabilities. The backbone degradable nanoparticles displayed high transfection efficiencies and low cytotoxicities in both 3T3 and HeLa 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.

Is it ATRP or SET-LRP? part I: Cu0&CuII/PMDETA – mediated reversible – deactivation radical polymerization

There is a controversial matter of debate as to the mechanism of the Cu0 catalyzed radical polymerization. Two models exist, one based upon ATRP whilst the other upon SET-LRP. Here we present new experimental results and insights into the nature of this polymerization. A good controlled/living polymerization was eventually obtained by Cu0&CuII/PMDETA-mediated radical polymerization. A comparative analysis shows that the mechanism behind this reaction lies between the competition and equilibrium results of SET-LRP and ATRP.

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.