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Lignin is a versatile biomass that possesses many different desirable properties such as antioxidant, antibacterial, anti-UV, and good biocompatibility. Natural lignin can be processed through several chemical processes. The processed lignin can be modified into functionalized lignin through chemical modifications to develop and enhance biomaterials. Thus, lignin is one of the prime candidate for various biomaterial applications such as drug and gene delivery, biosensors, bioimaging, 3D printing, tissue engineering, and dietary supplement additive. This review presents the potential of developing and utilizing lignin in the outlook of new and sustainable biomaterials. Thereafter, we also discuss on the challenges and outlook of utilizing lignin as a biomaterial., Graphical abstract Image 1, Highlights • Lignin's antioxidant, antibacterial, anti-UV and biocompatibility properties can be harnessed. • Modification and functionalization of lignin allows synthesis of enhanced biomaterials. • Biomedical applications of lignin-derived biomaterials include drug and gene delivery, biosensors, and tissue engineering.

The rise of antimicrobial-resistant bacteria strains has been a global public health concern due to their ability to cause increased patient morbidity and a greater burden on the healthcare system. As one of the potential solutions to overcome such bacterial infections, hyperbranched copolymers with cationic charges were developed. These copolymers were assessed for their antimicrobial efficacy and their bactericidal mechanisms. They were found to be potent against mobile colistin-resistant 1 strains, which was significant as colistin is known to be the last-resort antibiotic against Gram-negative bacteria. Furthermore, there was no sign of mutational resistance developed by E. Coli ATCC 25922 and MCR 1+ E. Coli against the copolymer even up to 20 passages. The ability to evade inducing resistance would provide invaluable insights for future antibiotic development. Our studies suggest that the bactericidal efficacy comes from the ability to target the outer membrane efficaciously. In vivo study using a Pseudomonas keratitis model showed that the copolymer was compatible with the eye and further supported that the copolymer treatment was effective for complete bacteria elimination.

Eco-friendly superhydrophobic polycaprolactone (PCL) membranes with hierarchical structure for efficient oil/water separation were fabricated via a simple and practical route. First, a series of hi...

Oxidative phosphorylation is an important biological process in the body to produce energy, during which oxygen free radicals are generated as byproduct. Excessive oxygen free radicals cause cell death and reduce the rate of tissue regeneration and healing in a wound. Lignin is a natural antioxidant derived from plants, but its biomedical application is restricted because of the uncertain biocompatibility. In this work, we developed a lignin-incorporated nanogel and explored its application for wound healing. Lignin was extracted from coconut husks and determined to have strong antioxidant activity (IC

Transparency is an important criterion for the application of biomaterials to the eye and essential for use as a vitreous substitute. However, there is a lack of understanding on the features of transparent hydrogels and the boundaries of transparency of various hydrogel systems. In this paper, we tune the poly[(R)-3-hydroxybutyrate-(R)-3-hydroxyhexanoate] (PHBHx) content of biodegradable PHBHx-based polyurethane thermogels and show that the amount of hydrophobic PHBHx correlates with hydrogel cloudiness. We found that PHxEP-0.5 hydrogel shows high light transmittance and suitable gel properties as a vitreous substitute. The PHxEP-0.5 hydrogel is able to maintain transparency when implanted in rabbit eyes as opposed to a cloudy gel and shows negligible inflammation and preservation of the retinal structure over 6 months. In conclusion, we show that PHBHx-based thermogels can be tuned for transparency and are biocompatible in the rabbit eye. These results could be instructive for the design of a new generation of injectable transparent vitreous substitutes.

Scaffolds for stem cell-based therapy of cartilage defect require bioactivity and stiffness mimicking to the native cartilage matrix. In this study, we fabricated electrospun nanofibers composited of cartilage matrix components (collagen or chondroitin sulfate) and poly(e-caprolactone)-polytetrahydrofuran (PCL-PTHF). PCL-PTHF with rat tail derived collagen was named PR and PCL-PTHF with chondroitin sulfate (PS) termed PS, which have a modulus of 7.5 MPa and 3.6 MPa, respectively, within the range of cartilage matrix. Their chondrogenic potential for guiding chondrogenic differentiation and promoting cartilage regeneration were investigated based upon mesenchymal stem cells (MSCs). Results showed that both PR and PS nanofibers have the ability to induce chondrogenesis of MSCs and accelerate the regeneration of injured cartilage surface, probably via the suppression of Tumor necrosis factor (TNF) signaling pathway as evidenced by microarray profiles. Comparatively, PR showed better chondrogenic potential both in vitro and in vivo than that of PS, which may induce chondrogenesis through Hypoxia inducing factor-1 (HIF-1) signaling pathway. This study may provide reference for MSC based therapy of cartilage defects.

Drug therapy of osteoarthritis (OA) is limited by the short retention and lacking of stimulus-responsiveness after intra-articular (IA) injection. The weak acid microenvironment in joint provides a potential trigger for controlled drug release systems in the treatment of OA. Herein, we developed an pH-responsive metal − organic frameworks (MOFs) system modified by hyaluronic acid (HA) and loaded with an anti-inflammatory protocatechuic acid (PCA), designated as MOF@HA@PCA, for the therapy of OA. Results demonstrated that MOF@HA@PCA could smartly respond to acidic conditions in OA microenvironment and gradually release PCA, which could remarkably reduce synovial inflammation in both IL-1β induced chondrocytes and the OA joints. MOF@HA@PCA also down-regulated the expression of inflammatory markers of OA and promoted the expression of cartilage-specific makers. This work may provide a new insight for the design of efficient nanoprobes for precision theranostics of OA .

Lignin, one of the most abundant biopolymers on Earth, has been recognized as a renewable alternative to traditional petroleum-based plastics. The integration of lignin with synthetic and engineering plastics is an important approach to develop sustainable polymers. However, it is challenging to blend lignin with other polymers due to its brittle nature and poor dispersion in many composites. In order to improve the miscibility and compatibility of lignin with other plastics, a series of poly(methyl methacrylate) (PMMA) grafted lignin copolymers were prepared from atom transfer radical polymerization. The chain length of PMMA oligomers and glass transition temperature of the lignin copolymers was controlled by varying the lignin: methyl methacrylate ratio. The lignin mass fractions in the copolymers varied from 5.6% to 46.1%. These lignin–PMMA copolymers were further blended with poly(e-caprolactone) (PCL) and engineered into nanofibrous composites by electrospinning. Tensile test and dynamical mechanical analysis showed that the incorporation of lignin–PMMA copolymers significantly improved the tensile strength, Young's modulus, and storage modulus of the resulting nanofibrous composites. The length of the PMMA chain played a crucial role in the miscibility of lignin in PCL, and therefore enhanced the stiffness and ultimate elongation of the resulting nanofibers. Cell culture studies suggested that these PCL/lignin–PMMA nanofibers were biocompatible and promoted the proliferation, attachment and interactions of human dermal fibroblasts. With reinforced mechanical properties and good biocompatibility, these green and stretchable electrospun nanofibers are potentially useful as biomaterial substrates for biomedical applications.

Poly(3-hydroxybutyrate) (PHB) is a sustainable and biodegradable biopolymer from bacteria, but its brittle nature greatly limits its applications. In this study, we developed a lignin-PHB copolymer to enhance the mechanical properties of PHB. β-Butyrolactone was grafted onto the lignin core by using solvent-free ring-opening polymerization (ROP). Then different amounts of lignin-PHB copolymers were blended into PHB and then engineered into nanofibers via electrospinning. The composite nanofibers with lignin-PHB copolymer exhibit much stronger mechanical properties than pure PHB fibers. Composite nanofibers with 2% lignin copolymer demonstrate the best mechanical performance with tensile strength increasing from 1.45 ± 0.36 MPa to 5.61 ± 0.63 MPa, Young's modulus increasing from 54.7 ± 1.2 MPa to 84.6 ± 10.0 MPa, and elongation increasing from 9.6 ± 2.2% to 93.5 ± 7.6%. Moreover, PHB/lignin nanofibers demonstrate tunable antioxidant activity, allowing the neutralization of excess free radicals in our body. Animal studies also demonstrate that the PHB/lignin nanofibers are nonirritating and biocompatible. Hence, these new PHB/lignin nanofibers hold great potential for biomedical applications.

Cartilage cannot self-repair and thus regeneration is a promising approach to its repair. Here we developed new electrospun nanofibers , made of poly (e-caprolactone)/polytetrahydrofuran (PCL-PTHF urethane) and collagen I from calf skin (termed PC), to trigger the chondrogenic differentiation of mesenchymal stem cells (MSCs) and the cartilage regeneration in vivo . We found that the PC nanofibers had a modulus (4.3 Mpa) lower than the PCL-PTHF urethane nanofibers without collagen I from calf skin (termed P) (6.8 Mpa) although both values are within the range of the modulus of natural cartilage (1–10 MPa). Both P and PC nanofibers did not show obvious difference in the morphology and size. Surprisingly, in the absence of the additional chondrogenesis inducers, the softer PC nanofibers could induce the chondrogenic differentiation in vitro and cartilage regeneration in vivo more efficiently than the stiffer P nanofibers. Using mRNA-sequence analysis, we found that the PC nanofibers outperformed P nanofibers in inducing chondrogenesis by specifically blocking the NF–kappa B signaling pathway to suppress inflammation. Our work shows that the PC nanofibers can serve as building blocks of new scaffolds for cartilage regeneration and provides new insights on the effect of the mechanical properties of the nanofibers on the cartilage regeneration.

Poly(3-hydroxybutyrate) (PHB) is an attractive biopolymer potential for various applications, but its brittle nature is a big handicap. In this study, we proposed lignin copolymers as mechanical reinforcement agents for PHB. A series of lignin copolymers (random and block) were synthesized via the solvent free ring-opening polymerization (ROP) of β-butyrolactone and/or e-caprolactone onto lignin core. The lignin copolymers were characterized by nuclear magnetic resonance (NMR), gel permeation chromatography (GPC) and differential scanning calorimetry (DSC). Next, these lignin copolymers were incorporated into PHB nanofibers as reinforcement fillers, in order to improve their mechanical properties. It is found that the lignin block copolymer with poly(e-caprolactone) (PCL) segment followed by PHB segment (LPC + H) displayed the best mechanical improvement. Tensile strength of PHB nanofibers enhanced from 1.81 MPa to 3.13 MPa, and elongation at break increased from 15% of 55%. In the reinforced system, lignin plays as a rigid core, PCL acts a rubbery layer and PHB segment forms strong bonding with fiber matrix. Moreover, PHB/lignin nanofibers were demonstrated with superior biodegradability and biocompatibility, indicating that the new nanofibrous system holds great potential for biomedical applications.

CpG oligodeoxynucleotides (CpG ODNs) bind to toll-like receptor 9 (TLR9) and activate the immune system. Thus, CpG ODNs have attracted considerable interest as immunotherapeutic agents or adjuvants for many diseases. Herein we report that polyethylenimine (PEI) functions as a multifunctional vector for both enhancing and regulating the immunostimulatory activity of CpG ODNs. PEI and CpG ODNs formed nanopolyplexes (NPs), which possessed good biocompatibility. PEI-CpG ODN NPs facilitated the internalization of CpG ODNs and induced increasing amounts of cytokines. Most importantly, PEI-CpG ODN NPs induced interleukin-6 (IL-6) and interferon-α (IFN-α) simultaneously, while class B CpG ODNs induced only IL-6. In contrast to class C CpG ODNs, which also simultaneously induce IFN-α and IL-6, the ratio of IFN-α and IL-6 induced by PEI-CpG ODN NPs could be regulated by changing the N/P ratio. This flexible bifurcated cytokine is promising for treating diseases such as cancer that require IL-6 and IFN-α simultaneously. Our findings propose a regulatory effect of PEI on the immunostimulatory activity of CpG ODNs, which will shed light on the development of highly efficient nonviral vectors for CpG ODN-based immunotherapy.

There are various concerns with current sunscreen actives in the sun care industry which pushes for a natural-based active that is sustainable as well as effective. Lignin is a natural polymer, capable of ultraviolet (UV) filtration and maintaining photostability. In this study, a variety of tuneable lignin-poly(ethylene glycol) (LP) nanodiamond (LP–ND) complexes were developed with varying ratios of LP to NDs. There are two fractions of LP–NDs, which use detonation NDs (LP–rNDs) and furnace NDs (LP–mNDs). Both complexes demonstrated favorable UV filtration, enhanced photostability, and uniform dispersion in water and cream. The LP–mND had maintained its particle size at

Rational design of new wound dressing materials aims to accelerate wound healing. Traditional hydrophilic wound dressings, however, tend to cause retention of wound exudate retention, which increases the risk of bacterial infection, resulting in slower wound healing. Herein, a multifunctional amphiphilic wound dressing nanofibrous materials with Janus superhydrophilic/ superhydrophobic feature is designed to accelerate wound healing. In this design, the top superhydrophilic polycaprolactone (PCL)-Gelatin (PCL-Gelatin, WCA ~ 0°) fibers function as a pump-like suction layer that can effectively isolate wound exudate from the wound site, thereby providing drier condition which lowers the risk of wound infection. More importantly, the superhydrophobic PCL-poly(perfluorodecyl methacrylate)-block-poly(dimethylsiloxane)-block-poly(perfluorodecyl methacrylate) (PFMA-b-PDMS-b-PFMA) (PCL-PFMA, WCA ~ 140°) in contact with the wound site showed excellent anti-adhesion effect to bacterial, cells and tissues, thereby further lowering the risk of bacterial infection and preventing the secondary injuries caused by dressing changes. Sprague-Dawley (SD) rat skin lesion model demonstrated significant improvement in wound healing of the Janus amphipathic PCL-Gelatin / PCL-PFMA fiber films compared with the conventional hydrophilic- and hydrophobic-only wound dressing materials. After 14 days of treatment, the wound healing area in this group was close to 100%. To the best our acknowledge, this is a pioneer exploration of Janus amphipathic wound dressing with unidirectional drainage function and anti-adhesive ability, which may have great potential for real life usage on clinical patients.

Lignin polymerization has been considered as an effective approach for lignin valorization. Herein we report the synthesis of a series of new lignin-based copolymers (lignin–poly(e-caprolactone-co-lactide), lignin–PCLLA) via solvent-free ring-opening polymerization. Lignin–PCLLA copolymers with tunable molecular weights (10 to 16 kDa) and glass transition temperatures (−40 to 40 °C) were obtained. Such copolymers were engineered into ultrafine nanofibers by blending with polyesters (polycaprolactone, PCL and poly(l-lactic acid), PLLA) via electrospinning. Both PCL/lignin–PCLLA and PLLA/lignin–PCLLA nanofibers displayed uniform and beadless nanofibrous morphology. The size (diameters ranging from 300 to 500 nm) and tensile tests of the obtained nanofibers indicated that the lignin copolymers are miscible with the polyester matrices and can significantly improve the mechanical properties of the nanofibers. Moreover, good antioxidant activity and biocompatibility of the lignin nanofibers were demonstrated in...

TiO2-based nanomaterials are among the most promising photocatalysts for degrading organic dye pollutants. In this work, Au–TiO2 nanofibers were fabricated by the electrospinning technique, followed by calcination in air at 500 °C. Morphological and structural analyses revealed that the composite consists of TiO2 nanofibers with embedded Au nanoparticles that are extensively distributed throughout the porous fibrous structure of TiO2. The photocatalytic performance of these Au-embedded TiO2 nanofibers was evaluated in the photodegradation of Rhodamine B and methylene blue under solar simulator irradiation. Compared with pristine TiO2 nanofibers, the Au-embedded TiO2 nanofibers displayed far better photocatalytic degradation efficiency. The plasmon resonance absorption of Au nanoparticles in the visible spectral region and the effective charge separation at the heterojunction of the Au–TiO2 hybrid are the key factors that have led to the considerable enhancement of the photocatalytic activity. The results of this study clearly demonstrate the potential of Au–TiO2 electrospun nanofibers as solar-light-responsive photocatalysts for the effective removal of dye contaminants from aquatic environments.

Biodegradable poly(lactic acid) (PLA)–lignin composites are considered to be promising renewable plastic materials toward a sustainable world. The addition of lignin to PLA may assist to combat the oxidative stress induced by PLA as biomaterials. In this study, PLA–lignin copolymers with various contents of alkylated lignin (10–50%) were synthesized by ring-opening polymerization. The molecular weight of such copolymers ranged from 28 to 75 kDa, while the PLA chain length varied from 5 to 38. These PLA–lignin copolymers were further blended with poly(l-lactide) (PLLA) and fabricated into nanofibrous composites by electrospinning. The PLLA/PLA–lignin nanofibers displayed uniform and bead-free nanostructures with fiber diameter of 350–500 nm, indicating the miscibility of PLLA and lignin copolymers in nanoscale. Unlike bulk materials, incorporation of PLA–lignin copolymers did not enhance the mechanical properties of the nanofibrous composites. Antioxidant assay showed that the lignin copolymers and PLLA/PL...

In situ gel delivery systems are preferred over conventional systems due to sustained and prolonged release action of therapeutic payload onto the targeted site. Thermogel, a form of in situ gel-forming polymeric formulation, undergoes sol-gel transition after administration into the body. At room temperature, the system is an aqueous polymer solution that easily entraps therapeutic payload by mixing. Upon injection, the higher physiological temperature causes gelation in situ because of the presence of thermosensitive polymers. The gel degrades gradually over time, allowing sustained release of therapeutics localized to the site of interest. This minimizes systemic toxicity and improved efficacy of drug release to the targeted site. Thermogel properties can be easily altered for specific applications via substitution and modification of components in diblock and triblock copolymer systems. The feasibility of fine-tuning allows modifications to biodegradability, biocompatibility, biological functionalization, mechanical properties, and drug release profile. This review summarized recent development in thermogel research with a focus on synthesis and self-assembly mechanisms, gel biodegradability, and applications for drug delivery, cell encapsulation and tissue engineering. This review also assessed inadequacy of material properties as a stand-alone factor on therapeutic action efficacy in human trials, with a focus on OncoGel, an experimental thermogel that demonstrated excellent individual or synergistic drug delivery system in preclinical trials but lacked therapeutic impact in human trials. Detailed analysis from all aspects must be considered during technology development for a successful thermogel platform in drug delivery and tissue engineering.

With an ever-increasing attention on the climate change and the growing amount of plastic wastes generated, the search for an alternative to the petroleum-based plastics has never been as imperative. Inspired by the structure of natural wood, we aim to reproduce artificial equivalent using modified lignin and cellulose acetate. As natural wood are made up of an aggregation of fibers, electrospinning was used to produce the fiber component. Besides exploring the influence of various polymers on the properties of the eventual fibers, its properties were also examined in terms of its orientation – random and aligned. The addition of lignin copolymers was shown to remarkably improve the tensile strength and the Young’s modulus of cellulose acetate fibers up to 500% and 7,000% respectively. In contrast to the random fibers, the aligned fibers demonstrated better tensile strength and Young’s modulus which could be attributed to the higher crystallinity. Among the fibers, the longitudinal aligned C.A. + Lig-PHB fibers exhibited the best tensile strength and Young’s modulus which could be explored for load bearing applications.

Electrospinning is a common method to prepare nanofiber scaffolds for tissue engineering. One of the common cellulose esters, cellulose acetate butyrate (CAB), has been electrospun into nanofibers and studied. However, the intrinsic hydrophobicity of CAB limits its application in tissue engineering as it retards cell adhesion. In this study, the properties of CAB nanofibers were improved by fabricating the composite nanofibers made of CAB and hydrophilic polyethylene glycol (PEG). Different ratios of CAB to PEG were tested and only the ratio of 2:1 resulted in smooth and bead-free nanofibers. The tensile test results show that CAB/PEG composite nanofibers have 2-fold higher tensile strength than pure CAB nanofibers. The hydrophobicity of the composite nanofibers was also reduced based on the water contact angle analysis. As the hydrophilicity increases, the swelling ability of the composite nanofiber increases by 2-fold with more rapid biodegradation. The biocompatibility of the nanofibers was tested with normal human dermal fibroblasts (NHDF). The cell viability assay results revealed that the nanofibers are non-toxic. In addition to that, CAB/PEG nanofibers have better cell attachment compared to pure CAB nanofibers. Based on this study, CAB/PEG composite nanofibers could potentially be used as a nanofiber scaffold for applications in tissue engineering.

Osteoarthritis (OA) is one of the most common musculoskeletal disorders worldwide. Oxidative stress initiated by excessive free radicals such as reactive oxygen species (ROS) is a leading cause of cartilage degradation and OA. However, conventional injection or oral intake of antioxidants usually cannot provide effective treatment due to rapid clearance and degradation or low bioavailability. Here, a new strategy is proposed based on nanofibers made of poly (ε-caprolactone) (PCL) and PCL-grafted lignin (PCL-g-lignin) copolymer. Lignin offers intrinsic antioxidant activity while PCL tailors the mechanical properties. Electrospun PCL-lignin nanofibers show excellent antioxidant activity, low cytotoxicity and excellent anti-inflammatory effects as demonstrated using both H2O2-stimulated human chondrocytes and an OA rabbit model. PCL-lignin nanofibers inhibit ROS generation and activate antioxidant enzymes through autophagic mechanism. Arthroscopic implantation of nanofibrous membrane of PCL-lignin is effective to OA therapy because it is biocompatible, biodegradable and able to provide sustained antioxidant activity. Agency for Science, Technology and Research (A*STAR) This study was financially supported by National key R&D program of China (2018YFC1105900), the Guangxi Science and Technology Base and Talent Special Project (Grant No. GuikeAD17129012), and the local Science and Technology Development Project leading by the central government (the three-D printing and digital medical platform, Grant No. GuikeZY18164004), High level innovation teams and outstanding scholars in Guangxi Universities (The third batch). The authors gratefully acknowledge the financial support from the Institute of Materials Research and Engineering (IMRE) under the Agency of Science, Technology and Research (A*STAR).

Cationic polymers remain attractive tools for non-viral gene transfer. The effectiveness of these vectors rely on the ability to deliver plasmid DNA (pDNA) into the nucleus of cells. While we have previously demonstrated the potential of Lignin-PGEA-PEGMA as a non-viral gene delivery vector, alterations of cellular phenotype and cytotoxicity were observed post transfection. The present study aims to explore transfection conditions for high efficiency and low toxicity of the Lignin-PGEA-PEGMA based gene delivery system. Cellular toxicity was significantly reduced by using the centrifugation protocol, which enables rapid deposition of DNA complexes. Replacement of media post centrifugation resulted in minimal exposure of cells to excess polymers, which were toxic to cells. At an optimized DNA amount (500–750 ng) and molar ratios of nitrogen (N) in polymer to phosphate (P) in pDNA (N/P = 30–40), with the use of a novel transfection enhancer that facilitates endosomal escape and nuclear trafficking, the efficiency of gene delivery was increased significantly 24 h post transfection. The present study demonstrated an appropriately optimized protocol that enabled the utility of a novel cationic polymer blend with a mixture of fusogenic lipids and a histone deacetylate inhibitor in non-viral transfection, thereby providing an attractive alternative to costly commercial gene carriers.

Antioxidant is critical for the successful of nerve tissue regeneration, and biomaterials with antioxidant activity might be favorable for peripheral nerve repair. Lignin, a biopolymer from wood with excellent antioxidant properties, is still “unexplored” as biomaterials. To design an antioxidative bioscaffold for nerve regeneration, here we synthesized lignin-polycaprolactone (PCL) copolymers via solvent free ring-opening polymerization (ROP). Then such lignin-PCL copolymers were incorporated with PCL and engineered into nanofibrous scaffolds for supporting the growth of neuron and Schwann cell. Our results showed that the addition of lignin-PCL enhanced the mechanical properties of PCL nanofibers and endowed them with good antioxidant properties (up to 98.3 ± 1.9% free radical inhibition within 4 h). Cell proliferation assay showed that PCL/lignin-PCL nanofibers increased cell viability compared to PCL fibers, especially after an oxidative challenge. Moreover, Schwann cells and dorsal root ganglion (DRG) neurons cultured on the nanofibers to assess their potential for nerve regeneration. These results suggested that nanofibers with lignin copolymers promoted cell proliferation of both BMSCs and Schwann cells, enhanced myelin basic protein expressions of Schwann cells and stimulated neurite outgrowth of DRG neurons. In all, these sustainable, intrinsically antioxidant nanofibers may be a potential candidate for nerve TE applications.

The desire for protection against UV exposure has resulted in the development of an increasing number of sunscreen agents. Lignin-based polymers have potential to serve as promising sunscreen agents as they have good UV absorption and antioxidant properties contributing towards the reduction of UV-induced skin damage. In this study, a series of lignin–poly(ethylene glycol) methacrylate (PEGMA) copolymers were synthesized via atom transfer radical polymerization (ATRP) to enhance the dispersion efficiency of lignin in the commercial creams. These copolymers showed tunability in both molecular weight (10–25 kDa) and particle size (100–200 nm), as well as excellent antioxidant properties. Different amounts of such copolymers were blended into commercial creams to investigate their sunscreen performance. Results indicated that adding lignin–PEGMA copolymers into sunblock creams improved their SPF values from 15.36 ± 2.44 to 38.53 ± 0.26. In summary, such lignin-based polymers with good UV protection and antioxidant properties offer a green alternative for developing the next generation of sunscreen creams.

In light of the incessant consumption of raw materials in the world today, the search for sustainable resources is ever pressing. Lignin, the second most naturally abundant biomass, which makes up 15% to 35% of the cell walls of terrestrial plants, has always been treated as waste and used in low-value applications such as heat and electricity generation. However, its abundance in nature could potentially solve the problem of the rapidly depleting resources if it was successfully translated into a renewable resource or valorized to higher value materials. Advanced lignin modification chemistry has generated a number of functional lignin-based polymers, which integrate both the intrinsic features of lignin and additional properties of the grafted polymers. These modified lignin and its copolymers display better miscibility with other polymeric matrices, leading to improved performance for these lignin/polymer composites. This review summarizes the progress in using such biopolymers as reinforcement fillers, antioxidants, UV adsorbents, antimicrobial agents, carbon precursors and biomaterials for tissue engineering and gene therapy. Recent developments in lignin-based smart materials are discussed as well.

The development of functional polymers from renewable lignin is attractive due to the depletion of fossil fuel and increasing environmental usage. A series of poly(ethylene glycol) methyl ether methacrylate (PEGMA)-grafted lignin hyperbranched copolymers were prepared by atom transfer radical polymerization (ATRP). The chemical structures, molecular characteristic and thermal properties of these copolymers were evaluated and such copolymers were prepared in a range of molecular weights from 38.7 to 65.0 kDa by adjusting the PEGMA-to-lignin weight ratio. As a result from their hyperbranch architecture, their aqueous solutions were found to form supramolecular hydrogels with a very low critical gelation concentration of 1 wt % copolymers, in the presence of α-cyclodextrin (α-CD). The rheological properties of the supramolecular assemblies were investigated and these hydrogel systems showed tunable mechanical response and excellent self-healing capability. Combined with good biocompatibility, these new types...

The dinuclear complex [Cu2 I2 (L1)2 ] (1) (L1=3-((4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl)methyl)benzonitrile) is characterized by single-crystal X-ray diffraction (XRD), powder XRD, IR, photoluminescence spectroscopy, and thermogravimetric analysis. Unlike other related, known copper iodide complexes, it exhibits strong yellow emission in the solid state at both room temperature and 77 K. Showing good compatibility with PMMA, it is blended with the polymer in different weight ratios to prepare luminescent composite fibers.

Heart disease, especially myocardial infarction (MI), has become the leading cause of death all over the world, especially since the myocardium lacks the ability to regenerate after infarction. The capability of mesenchymal stem cells (MSCs) to differentiate into the cardiac lineage holds great potential in regenerative medicine for MI treatment. In this study, we investigated the potential of human MSCs (hMSCs) to differentiate into cardiomyogenic cell lineages, using 5-azacytidine (5-aza) on electrospun poly(e-caprolactone)-gelatin (PCL-gelatin) nanofibrous scaffolds. Immunofluorescence staining analysis showed that after 15 days of in vitro culture the hMSCs differentiated to cardiomyogenic cells on PCL-gelatin (PG) nanofibers and expressed a higher level of cardiac-specific proteins, such as α-actinin and troponin-T, compared to the MSC-differentiated CMs on tissue culture plates (control). To further induce the cardiac differentiation, vascular endothelial growth factor (VEGF) was incorporated into the nanofibers by blending or co-axial electrospinning, and in vitro release study showed that the growth factor could cause sustained release of VEGF from the nanofibers for a period of up to 21 days. The incorporation of VEGF within the nanofibers improved the proliferation of MSCs and, more importantly, enhanced the expression of cardiac-specific proteins on PG-VEGF nanofibers. Our study demonstrated that the electrospun PG nanofibers encapsulated with VEGF have the ability to promote cardiac differentiation of hMSCs, and might be promising scaffolds for myocardial regeneration. Copyright © 2015 John Wiley & Sons, Ltd.

The interpenetrating alginate-based hybrid hydrogel network is a tough yet recoverable material. This is believed to be caused by the combination of the strength of a covalent network, and the reversibility of an ionic network. However, hydrogen bonds are believed to also be responsible for the exceptional properties of these hydrogels. In this paper, the effect of varying the reactant concentrations on the mechanical properties of the hydrogels was first studied. By changing the monomer used (from polyacrylamide to polydimethylacrylamide) in the fabrication of the hydrogel, the effect of hydrogen bonding was studied. Compression test results showed that the presence of hydrogen bonds is critical for the high toughness of the hybrid hydrogel. Additionally, co-polymeric hybrid hydrogels were synthesized and shown to have improved mechanical properties over the original hybrid hydrogel, with an elastic modulus and compressive toughness of 350 kPa and 70 J m−3, respectively. The results of this experiment can be used to optimise the mechanical properties of future hybrid hydrogels.

A lignin-based copolymer with good biocompability was successfully prepared via atom transfer radical polymerization (ATRP) for efficient gene delivery. Kraft lignin was modified into lignin-based macroinitiators and then poly(glycidyl methacrylate)-co-poly(ethylene glycol)methacrylate (PGMA-PEGMA) side chains were prepared via ATRP grafting onto lignin. Ethanolamine was sequentially functionalized onto lignin-PGMA-PEGMA and a cationic lignin-PGEA-PEGMA copolymer consisting of a lignin core and different-length PGEA-PEGMA side chains was produced. Lignin-PGEA-PEGMA copolymers could efficiently compact pDNA into nanoparticles with sizes ranging from 150 to 250 nm at N/P ratios of 10 or higher. The gene transfection efficiency depends greatly on the mass percentage of PGEA units and the N/P ratio. The lignin-PGEA-PEGMA with 46.9% (mass%) of PGEA units (i.e. LG100) has highest transfection efficiency in comparison with the copolymers with a lower amount of PGEA units. In addition, LG100 has high transfection efficiency under serum conditions, which is comparable to or much higher than PEI control in HEK 293T and Hep G2 cell lines. More importantly, lignin-PGEA-PEGMA copolymers have excellent antioxidant activity. The novel cationic lignin-PGEA-PEGMA copolymers can be promising gene carriers for gene delivery.

Natural polysaccharide pectin has for the first time been grafted with polyhydroxybutyrate (PHB) via ring-opening polymerization of β-butyrolactone. This copolymer, pectin-polyhydroxybutyrate (pec-PHB), was blended with PHB in various proportions and electrospun to produce nanofibers that exhibited uniform and bead-free nanostructures, suggesting the miscibility of PHB and pec-PHB. These nanofiber blends exhibited reduced fiber diameters from 499 to 336–426 nm and water contact angles from 123.8 to 88.2° on incorporation of pec-PHB. They also displayed 39–335% enhancement of elongation at break relative to pristine PHB nanofibers. pec-PHB nanofibers were found to be noncytotoxic and biocompatible. Human retinal pigmented epithelium (ARPE-19) cells were seeded onto pristine PHB and pec-PHB nanofibers as scaffold and showed good proliferation. Higher proportions of pec-PHB (pec-PHB10 and pec-PHB20) yielded higher densities of cells with similar characteristics to normal RPE cells. We propose, therefore, that nanofibers of pec-PHB have significant potential as retinal tissue engineering scaffold materials.

The potential of pluripotent embryonic stem cells (ESCs) isolated from the inner mass of blastocysts are investigated for its ability to differentiate on biocompatible electrospun nanofibers, for regeneration of the myocardially infracted heart. Nanostructured poly(d,l-lactide-co-glycolide)/collagen (PLGA/Col) scaffolds with fiber diameters in the range of 300 ± 65 nm, was fabricated by electrospinning to mimic the extracellular matrix of the native tissue. During the culture of embryoid bodies outgrowth on the scaffolds, and further differentiation of ESCs to cardiomyocytes, the PLGA/Col nanofibers was found better than that of the electrospun PLGA nanofibers, where a better interaction and growth of ESC differentiated cardiomyocytes was observed on the composite scaffolds. The phenotypical characteristics of ESC-derived cardiomyocytes and molecular protein expression were carried out by scanning electron microscopy and immunocytochemistry, respectively. Our studies highlight the significance of a suitable material, its architecture, and cell–biomaterial interactions that is essential at a nanoscale level signifying the application of a bioengineered cardiac graft for stem cell differentiation and transplantation, which could be an intriguing strategy for cardiac regeneration. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 447–454, 2014.

Thermogels are stimuli-responsive soft materials which undergo sol–gel transition with temperature changes. The gel is fluid at room temperature and can be blended with therapeutics by mixing. The higher physiological temperature that a gel encounters upon injection results in gelation due to the presence of thermosensitive polymers. The degradation of the gel allows sustained release of therapeutics localized to the site of interest. Thermogel properties, such as biodegradability, biocompatibility, biological functionalization, mechanical properties and the therapeutic release profile, can be fine-tuned via the substitution and modification of components in these diblock and triblock copolymer systems. This chapter examines the key concepts behind the technology development of these thermogels to successfully translate thermogels for therapeutic conveyance and tissue repair and replacement.

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(e-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 ± 138 nm, 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.

In light of the incessant consumption of raw materials in the world today, the search for sustainable resources is ever pressing. Lignin, the second most naturally abundant biomass, which makes up 15% to 35% of the cell walls of terrestrial plants, has always been treated as waste and used in low-value applications such as heat and electricity generation. However, its abundance in nature could potentially solve the problem of the rapidly depleting resources if it was successfully translated into a renewable resource or valorized to higher value materials. Advanced lignin modification chemistry has generated a number of functional lignin-based polymers, which integrate both the intrinsic features of lignin and additional properties of the grafted polymers. These modified lignin and its copolymers display better miscibility with other polymeric matrices, leading to improved performance for these lignin/polymer composites. This review summarizes the progress in using such biopolymers as reinforcement fillers, antioxidants, UV adsorbents, antimicrobial agents, carbon precursors and biomaterials for tissue engineering and gene therapy. Recent developments in lignin-based smart materials are discussed as well.

Silver nanoparticles (AgNPs) and silver ions (Ag(+)) show growth-inhibitory activity against microorganisms and have been used for decades as antibacterial agents in various fields. To fabricate a nanofibrous scaffold which is antibacterial against bacteria and non-toxic to cells, we electrospun composite poly(L-lactic acid)-co-poly(ϵ-caprolactone) nanofibres containing silver nanoparticles (PLLCL-AgNPs) with different concentrations (0.25, 0.50 and 0.75 wt%) of silver nitrate (AgNO3) in PLLCL. The diameters of the electrospun PLLCL-AgNPs nanofibres decreased with the increase of AgNO3 concentration in PLLCL solutions. Human skin fibroblasts cultured on the scaffolds showed that the PLLCL nanofibres containing lesser amounts of AgNPs (0.25 wt%) had better cell proliferation and retained the cell morphology similar to the phenotype observed on tissue culture plates (control). The antibacterial activity of AgNPs in PLLCL nanofibres was investigated against Staphylococcus aureus and Salmonella enterica and the antimicrobial activity was found to increase with the increasing concentration of nanoparticles present in the scaffold. Based on our studies, we propose that PLLCL nanofibres containing 0.25 wt% AgNO3 or PLLCL-Ag(25), favors cell proliferation and inhibits bacteria and could be a suitable substrate for wound healing.

A biocompatible and elastomeric nanofibrous scaffold is electrospun from a blend of poly(1,8-octanediol-co-citrate) [POC] and poly(L-lactic acid) -co-poly-(3-caprolactone) [PLCL] for application as a bioengineered patch for cardiac tissue engineering. The characterization of the scaffolds was carried out by Fourier transform infra red spectroscopy, scanning electron microscopy (SEM), and tensile measurement. The mechanical properties of the scaffolds are studied with regard to the percentage of POC incorporated with PLCL and the results of the study showed that the mechanical property and degradation behavior of the composites can be tuned with respect to the concentration of POC blended with PLCL. The composite scaffolds with POC: PLCL weight ratio of 40:60 [POC/PLCL4060] was found to have a tensile strength of 1.04 ± 0.11 MPa and Young's Modulus of 0.51 ± 0.10 MPa, comparable to the native cardiac tissue. The proliferation of cardiac myoblast cells on the electrospun POC/PLCL scaffolds was found to increase from Days 2 to 8, with the increasing concentration of POC in the composite. The morphology and cytoskeletal observation of the cells also demonstrated the biocompatibility of the POC containing scaffolds. Electrospun POC/PLCL4060 nanofibers are promising elastomeric substrates that might provide the necessary mechanical cues to cardiac muscle cells for regeneration of the heart. © 2012 Wiley Periodicals, Inc. Biopolymers 97:529–538, 2012.

Emulsion electrospinning is a novel approach to fabricate core–shell nanofibers, and it is associated with several advantages such as the alleviation of initial burst release of drugs and it protects the bioactivity of incorporated drugs or proteins. Aiming to develop a sustained release scaffold which could be a promising substrate for cardiovascular tissue regeneration, we encapsulated vascular endothelial growth factor (VEGF) with either of the protective agents, dextran or bovine serum albumin (BSA) into the core of poly(l-lactic acid-co-e-caprolactone) (PLCL) nanofibers by emulsion electrospinning. The morphologies and fiber diameters of the emulsion electrospun scaffolds were determined by scanning electron microscope, and the core–shell structure was evaluated by laser scanning confocal microscope. Uniform nanofibers of PLCL, PLCL–VEGF–BSA, and PLCL–VEGF–DEX with fiber diameters in the range of 572 ± 92, 460 ± 63, and 412 ± 61 nm, respectively were obtained by emulsion spinning. The release profile of VEGF in phosphate-buffered saline for up to 672 h (28 days) was evaluated, and the scaffold functionality was established by performing cell proliferations using human bone marrow derived mesenchymal stem cells. Results of our study demonstrated that the emulsion electrospun VEGF containing core–shell structured PLCL nanofibers offered controlled release of VEGF through the emulsion electrospun core–shell structured nanofibers and could be potential substrates for cardiac tissue regeneration.

An injectable calcium phosphate cement (CPC) with porous structure and excellent anti-washout ability was developed in the study. Citric acid and sodium bicarbonate were added into the CPC powder consisting of tetracalcium phosphate (TTCP) and dicalcium phosphate dihydrate (DCPD) to form macro-pores, then different concentrations of sodium hyaluronate (NaHA) solution, as liquid phase, was added into the cement to investigate its effect on CPC's performance. The prepared CPCs were tested on workability (injectable time and setting time), mechanical strength, as well as anti-washout ability. The experimental results showed that addition of NaHA not only enhanced the anti-washout ability of the CPC dramatically but also improve its other properties. When NaHA concentration was 0.6 wt%, the injectable time elongated to 15.7 +/- 0.6 min, the initial and final setting times were respectively shorten to 18.3 +/- 1.2 and 58.7 +/- 2.1 min, and the compressive strength were increased to 18.78 +/- 1.83 MPa. On the other hand, Addition of NaHA showed little effect on porous structure of the CPC and enhanced its bioactivity obviously, which was confirmed by the apatite formation on its surface after immersion in simulated body fluid (SBF). In conclusion, as an in situ shaped injectable biomaterials, the CPC with appropriate addition of NaHA would notably improve its performance and might be used in minimal invasive surgery for bone repair or reconstruction.

In the present study, three types of tetracalcium phosphate (TTCP) were prepared by solid-solid reaction or co-precipitation method and by different cooling modes. The effect of TTCP on the performance of calcium phosphate cement (CPC) was investigated. The result showed that the characteristic of TTCP varied with preparation method and played an important role in CPC performance. A solid-solid reacted TTCP yielded smaller particle size and resulted in bad workability and mechanical strength of CPC. The fast cooling of sintering TTCP by liquid nitrogen could avoid the decomposition of TTCP and make pure TTCP. TTCP prepared by wet-precipitation could improve performance of CPC and was promising to optimization of CPC.

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. ASTAR (Agency for Sci., Tech. and Research, S’pore) MOE (Min. of Education, S’pore) Accepted version

With advances in the field of tissue engineering, it is increasingly recognized that biodegradable and biocompatible scaffolds incorporated with multiple wound healing mediators might serve as the most promising medical devices for skin tissue regeneration. Through controlled drug delivery, these medical devices can reduce the toxicity effects and optimize clinical efficiency. In this study, we first encapsulated multiple epidermal induction factors (EIF) such as the epidermal growth factor (EGF), insulin, hydrocortisone, and retinoic acid (RA) with gelatin and poly( l -lactic acid)-co-poly-(e-caprolactone) (PLLCL) solutions and performed electrospinning by two different approaches: blend spinning and core–shell spinning. No burst release was detected from EIF encapsulated core–shell nanofibers; however, an initial 44.9% burst release from EIF blended nanofibers was observed over a period of 15 days. The epidermal differentiation potential of adipose-derived stem cells (ADSCs) was evaluated for EIF-containing scaffolds prepared either by core–shell spinning or by blend spinning. After 15 days of cell culture, the proliferation of ADSCs on EIF encapsulated core–shell nanofibers was the highest. Moreover, a higher percentage of ADSCs got differentiated to epidermal lineages on EIF encapsulated core–shell nanofibers compared to the cell differentiation on EIF blended nanofibers, which can be attributed to the sustained release of EIF from the core–shell nanofibers. Our study demonstrated that the EIF encapsulated core–shell nanofibers might serve as a promising tissue engineered graft for skin regeneration.

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(e-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.

Use of plant extracts for treatment of burns and wound is a common practice followed over the decades and it is an important aspect of health management. Many medicinal plants have a long history of curative properties in wound healing. Electrospun nanofibers provide high porosity with large surface area-to-volume ratio and are more appropriate for cell accommodation, nutrition infiltration, gas exchange and waste excretion. Electrospinning makes it possible to combine the advantages of utilizing these plant extracts in the form of nanofibrous mats to serve as skin graft substitutes. In this study, we investigated the potential of electrospinning four different plant extracts, namely Indigofera aspalathoides, Azadirachta indica, Memecylon edule (ME) and Myristica andamanica along with a biodegradable polymer, polycaprolactone (PCL) for skin tissue engineering. The ability of human dermal fibroblasts (HDF) to proliferate on the electrospun nanofibrous scaffolds was evaluated via cell proliferation assay. HDF proliferation on PCL/ME nanofibers was found the highest among all the other electrospun nanofibrous scaffolds and it was 31% higher than the proliferation on PCL nanofibers after 9 days of cell culture. The interaction of HDF with the electrospun scaffold was studied by F-actin and collagen staining studies. The results confirmed that PCL/ME had the least cytotoxicity among the different plant extract containing scaffolds studied here. Therefore we performed the epidermal differentiation of adipose derived stem cells on PCL/ME scaffolds and obtained early and intermediate stages of epidermal differentiation. Our studies demonstrate the potential of electrospun PCL/ME nanofibers as substrates for skin tissue engineering.