Sing Shy Liow

Biodegradable polymers for electrospinning: towards biomedical applications.

Electrospinning has received much attention recently due to the growing interest in nano-technologies and the unique material properties. This review focuses on recent progress in applying electrospinning technique in production of biodegradable nanofibers to the emerging field of biomedical. It first introduces the basic theory and parameters of nanofibers fabrication, with focus on factors affecting the morphology and fiber diameter of biodegradable nanofibers. Next, commonly electrospun biodegradable nanofibers are discussed, and the comparison of the degradation rate of nanoscale materials with macroscale materials are highlighted. The article also assesses the recent advancement of biodegradable nanofibers in different biomedical applications, including tissue engineering, drug delivery, biosensor and immunoassay. Future perspectives of biodegradable nanofibers are discussed in the last section, which emphasizes on the innovation and development in electrospinning of hydrogels nanofibers, pore size control and scale-up productions.

Long-Term Real-Time In Vivo Drug Release Monitoring with AIE Thermogelling Polymer

A new drug concentration meter is developed. In vivo drug release can be monitored precisely via a self-indicating drug delivery system consisting of a new aggregation-induced emission thermoresponsive hydrogel. By taking the advantage of a self-indicating system, one can easily detect the depletion of drugs, and reinject to maintain a dosage in the optimal therapeutic window.

Biodegradable Thermogelling Polymers: Working Towards Clinical Applications

As society ages, aging medical problems such as organ damage or failure among senior citizens increases, raising the demand for organ repair technologies. Synthetic materials have been developed and applied in various parts of human body to meet the biomedical needs. Hydrogels, in particular, have found extensive applications as wound healing, drug delivery and controlled release, and scaffold materials in the human body. The development of the next generation of soft hydrogel biomaterials focuses on facile synthetic methods, efficacy of treatment, and tunable multi-functionalities for applications. Supramolecular 3D entities are highly attractive materials for biomedical application. They are assembled by modules via various non-covalent bonds (hydrogen bonds, p-p stacking and/or van der Waals interactions). Biodegradable thermogels are a class of such supramolecular assembled materials. Their use as soft biomaterials and their related applications are described in this Review.

Elastic poly(ε-caprolactone)-polydimethylsiloxane copolymer fibers with shape memory effect for bone tissue engineering.

A porous shape memory scaffold with biomimetic architecture is highly promising for bone tissue engineering applications. In this study, a series of new shape memory polyurethanes consisting of organic poly(ε-caprolactone) (PCL) segments and inorganic polydimethylsiloxane (PDMS) segments in different ratios (9 : 1, 8 : 2 and 7 : 3) was synthesised. These PCL-PDMS copolymers were further engineered into porous fibrous scaffolds by electrospinning. With different ratios of PCL: PDMS, the fibers showed various fiber diameters, thermal behaviour and mechanical properties. Even after being processed into fibrous structures, these PCL-PDMS copolymers maintained their shape memory properties, and all the fibers exhibited excellent shape recovery ratios of  >90% and shape fixity ratios of  >92% after 7 thermo-mechanical cycles. Biological assay results corroborated that the fibrous PCL-PDMS scaffolds were biocompatible by promoting osteoblast proliferation, functionally enhanced biomineralization-relevant alkaline phosphatase expression and mineral deposition. Our study demonstrated that the PCL-PDMS fibers with excellent shape memory properties are promising substrates as bioengineered grafts for bone regeneration.

PHB-Based Gels as Delivery Agents of Chemotherapeutics for the Effective Shrinkage of Tumors

Injectable thermogel to deliver chemotherapeutics in a minimally invasive manner and to achieve their long term sustained release at tumor sites to minimize side effects is attractive for chemotherapy and precision medicine, but its rational design remains a challenge. In this work, a copolymer with natural biodegradable poly[(R)-3-hydroxybutyrate] (PHB), hydrophilic poly(ethylene glycol), and temperature sensitive poly(propylene glycol) blocks linked by urethane linkages is designed to show thermogelling characteristics which are beneficial for minimally invasive injection and safe degradation. This thermogelling polymer possesses in vitro biocompatibility with very low cyto-toxicity in HEK293 cells. Furthermore, it is able to form the gel to achieve the controllable release of paclitaxel (PTX) and doxorubicin (DOX) by adjusting polymer concentrations. A rodent model of hepatocarcinoma has been performed to demonstrate the in vivo applications of this PHB-based thermogel. The drug-loaded thermogel has been intratumorally injected and both PTX-loaded and DOX-loaded thermogel have significantly slowed down tumor growth. This work represents the first time that injectable PHB thermogels have possessed good controllable release effect of chemotherapeutics against the in vivo model of tumors and will benefit various applications, including on-demand drug delivery and personalized medicine.

Biocompatible electrically conductive nanofibers from inorganic-organic shape memory polymers

A porous shape memory scaffold with both biomimetic structures and electrical conductivity properties is highly promising for nerve tissue engineering applications. In this study, a new shape memory polyurethane polymer which consists of inorganic polydimethylsiloxane (PDMS) segments with organic poly(ε-caprolactone) (PCL) segments was synthesized. Based on this poly(PCL/PDMS urethane), a series of electrically conductive nanofibers were electrospun by incorporating different amounts of carbon-black. Our results showed that after adding carbon black into nanofibers, the fiber diameters increased from 399±76 to 619±138nm, the crystallinity decreased from 33 to 25% and the resistivity reduced from 3.6 GΩ/mm to 1.8 kΩ/mm. Carbon black did not significantly influence the shape memory properties of the resulting nanofibers, and all the composite nanofibers exhibited decent shape recovery ratios of >90% and shape fixity ratios of >82% even after 5 thermo-mechanical cycles. PC12 cells were cultured on the shape memory nanofibers and the composite scaffolds showed good biocompatibility by promoting cell-cell interactions. Our study demonstrated that the poly(PCL/PDMS urethane)/carbon-black nanofibers with shape memory properties could be potentially used as smart 4-dimensional (4D) scaffolds for nerve tissue regeneration.

New Linear and Star‐Shaped Thermogelling Poly([R]‐3‐hydroxybutyrate) Copolymers

The synthesis of multi-arm poly([R]-3-hydroxybutyrate) (PHB)-based triblock copolymers (poly([R]-3-hydroxybutyrate)-b-poly(N-isopropylacrylamide)-b-[[poly(methyl ether methacrylate)-g-poly(ethylene glycol)]-co-[poly(methacrylate)-g-poly(propylene glycol)]], PHB-b-PNIPAAM-b-(PPEGMEMA-co-PPPGMA), and their subsequent self-assembly into thermo-responsive hydrogels is described. Atom transfer radical polymerization (ATRP) of N-isopropylacrylamide (NIPAAM) followed by poly(ethylene glycol) methyl ether methacrylate (PEGMEMA) and poly(propylene glycol) methacrylate (PPGMA) was achieved from bromoesterified multi-arm PHB macroinitiators. The composition of the resulting copolymers was investigated by (1) H and (13) C J-MOD NMR spectroscopy as well as size-exclusion chromatography (SEC), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The copolymers featuring different architectures and distinct hydrophilic/hydrophobic contents were found to self-assemble into thermo-responsive gels in aqueous solution. Rheological studies indicated that the linear one-arm PHB-based copolymer tend to form a micellar solution, whereas the two- and four-arm PHB-based copolymers afforded gels with enhanced mechanical properties and solid-like behavior. These investigations are the first to correlate the gelation properties to the arm number of a PHB-based copolymer. All copolymers revealed a double thermo-responsive behavior due to the NIPAAM and PPGMA blocks, thus allowing first the copolymer self-assembly at room temperature, and then the delivery of a drug at body temperature (37 °C). The non-significant toxic response of the gels, as assessed by the cell viability of the CCD-112CoN human fibroblast cell line with different concentrations of the triblock copolymers ranging from 0.03 to 1 mg mL(-1) , suggest that these PHB-based thermo-responsive gels are promising candidate biomaterials for drug-delivery applications.

Cationic Micelles Based on Polyhedral Oligomeric Silsesquioxanes for Enhanced Gene Transfection

The synthesis and gene transfection efficiency of a series of amphiphilic copolymers, poly(2-(dimethylamino)ethyl methacrylate)-poly (methacrylate isobutyl polyhedral oligomeric silsesquioxane) (PDMAEMA-POSS) copolymers are reported. The hydrophobic POSS interior allows a cell-sensitizing drug such as paclitaxel to be incorporated, whereas the cationic and hydrophilic PDMAEMA corona allows the complexation of anionic DNA to form a nano-sized polyplex. These drug-encapsulated copolymers display excellent gene transfection efficiency compared with polyethylenimine or PDMAEMA homopolymers.

Thermoplastic biodegradable elastomers based on ε-caprolactone and l-lactide block co-polymers: A new synthetic approach

Although biodegradable polymers have found extensive application in medical devices, there are very few commercially available elastomeric biodegradable polymers. In this work, starting with the well-known monomers L-lactide and ε-caprolactone, we developed elastomers using a multiblock co-polymer approach. This ensures that the degradation products of such elastomers are also acceptable from a cytotoxicity standpoint. A series of polymers with various structures was synthesized utilizing a design of experiment approach. The basic structure is that of a diblock, with each block being modified by the addition of co-monomer. The synthesized polymers exhibited a range of mechanical properties from a typical thermoplastic polymer to that approaching a good thermoplastic elastomer. 13C nuclear magnetic resonance analysis, size exclusion chromatography and differential scanning calorimetry measurements have been utilized to relate the observed range of mechanical properties to the structure. In addition, the elastomeric nature has been established with the use of creep and recovery measurements. Such elastomers may find a variety of biomedical applications, ranging from stent coatings to atrial septal defect occluders.

Synthesis of a new poly([R]-3-hydroxybutyrate) RAFT agent

Poly[(R)-3-hydroxybutyrate] (PHB) has attracted more and more attention in biomedical applications in recent years, due to its excellent properties of sustainability, biodegradability and biocompatibility. In this work, purified natural PHB was modified by 1-hexanol through transesterification reaction to form mono-hydroxylated PHB. The kinetic process of transesterification was carefully investigated. The mono-hydroxylated PHB was reacted with the thiocarbonylthio compound to generate a biodegradable macro mono-hydroxylated PHB chain transfer agent (CTA), which could react with other monomers to produce block copolymers. The monomer, 2-dimethylaminoethyl methacrylate (DMAEMA) was chosen to demonstrate the copolymerization process and the block copolymer PHB-b-PDMAEMA was obtained.