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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.

SQR29 organophotosensitizer was encapsulated into poly(lignin/PEG/PPG urethane) to form a hydrogel (LSQR29), providing excellent antibacterial photodynamic therapy (aPDT) property to combat antibiotic-resistant pathogenic bacteria in wound infection.

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.

A high prevalence of middle one-third clavicle fracture has been reported. Both superior and anterior clavicle plates have been used in clinical and biomechanical research, but no decisive advantage for either design has been reported. Spiral clavicle plates have not been well studied in terms of their structural stability and implant safety. The present study analyses the multi-directional biomechanical performance of spiral clavicle plates using the finite element method. Two commercial spiral clavicle plate designs were reconstructed to simulate the surgical reduction of a middle one-third oblique clavicle fracture (OTA classification: 15-B1.2). Mechanical load, including axial compression, inferior bending, and axial torsion, was applied to evaluate the multi-directional structural stability and implant safety of the plates. The two spiral clavicle plate designs enhanced structural stiffness under axial compression, inferior bending, and axial torsion by 59–71%, 38–82%, and 31–46%, respectively, compared to that of the intact clavicle model. Stress concentrations were found around the reconstruction feature of the plate and the screw hole, especially under inferior bending. The improvement in multi-directional biomechanical stability provided by a spiral clavicle plate is worth considering in clinical applications. Implant safety should be further investigated based on mechanical tests and clinical observations.

Iron oxide nanomaterials with mimic enzymes activity have been paid more attention in the clinical diagnosis field. The modified surface molecules would influence the catalytic activity of nanozyme, which is worth studying. Furthermore, the traditional detection strategy is based on colorimetric change of substrates, however, the optical signal is easy to be interfered in complex biological applications. In our research, an efficient and facile preparation strategy was developed to obtain functional artificial nanozymes. Herein, three kinds of surfactants, including citrate acid, poly(ethylene glycol) bis (carboxymethyl) ether and tannic acid have been applied to modify these nanomaterials that showed uniform size, high soluble dispersity and stability. Furthermore, these nanozymes exhibited different peroxidase-like activity to catalyze the hydrogen peroxide and 3,3′,5,5′-tetramethylbenzidine. More importantly, magnetic relaxation effect of iron oxide nanozymes was found to be changed during the catalytic reaction. In addition, the relationship between the magnetic signal of nanozymes and the substrate concentration showed a good linear dependence. Combined with the natural enzymes, the magnetic detection of iron oxide nanozymes also exhibited excellent substrate specificity. On these bases, a dual-function specific assay was constructed and further used for glucose detection. In conclusion, this study demonstrated an efficient iron oxide nanozymes preparation method and constructed a new synergistically colorimetric-magnetic diagnosis strategy.

Background Osteoarthritis (OA) is common musculoskeletal disorders associated with overgeneration of free radicals, and it causes joint pain, inflammation, and cartilage degradation. Lignin as a natural antioxidant biopolymer has shown its great potential for biomedical applications. In this work, we developed a series of lignin-based nanofibers as antioxidative scaffolds for cartilage tissue engineering. Results The nanofibers were engineered by grafting poly(lactic acid) (PLA) into lignin via ring-opening polymerization and followed by electrospinning. Varying the lignin content in the system was able to adjust the physiochemical properties of the resulting nanofibers, including fiber diameters, mechanical and viscoelastic properties, and antioxidant activity. In vitro study demonstrated that the PLA-lignin nanofibers could protect bone marrow-derived mesenchymal stem/stromal cells (BMSCs) from oxidative stress and promote the chondrogenic differentiation. Moreover, the animal study showed that the lignin nanofibers could promote cartilage regeneration and repair cartilage defects within 6 weeks of implantation. Conclusion Our study indicated that lignin-based nanofibers could serve as an antioxidant tissue engineering scaffold and facilitate the cartilage regrowth for OA treatment. Graphical Abstract

Hydrogels composed from biomolecules have gained great interests as biomaterials for tissue engineering. However, their poor mechanical properties limit their application potential. Here, we synthesized a series of tough composite hydrogels from poly (vinyl alcohol) (PVA) and pectin for bone tissue engineering. With a balance of scaffold stiffness and pore size, PVA-Pec-10 hydrogel enhanced adhesion and proliferation of osteoblasts. The hydrogel significantly promoted osteogenesis

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.

Myocardial tissue engineering offers a novel technology to improve or regenerate cardiac functions using a combination of cells, biomaterials and engineering strategies. Inspired by low-resistance pathways for electrical signal propagation in the native heart tissue, electrically conductive nanofibrous scaffolds composed of melanin, poly(L-lactide-co-e-caprolactone) and gelatin were fabricated to provide electrophysiological cues to cardiac myocytes and mimic the native myocardial environment. Our results show that by increasing the concentration of melanin to 40% within the composite, the fiber diameters reduced to 153 ± 30 nm, modulus decreased to 7.1 ± 0.6 MPa, and conductance increased to 259.51 ± 187.60 μS cm−1. Results of cell proliferation and immunostaining analysis of human cardiac myocytes demonstrated that the conductive nanofibers containing 10% melanin promote cell interaction with expression of cardiac-specific proteins compared to other scaffolds. Electrical stimulation through the scaffolds showed enhanced cell proliferation and the expression of connexin-43, signifying the potential of using melanin containing nanofibers as a suitable cardiac patch for the regeneration of infarct myocardium.

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.

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.

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.

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.

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.

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.

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.

The potential of cardiomyogenic differentiation of human mesenchymal stem cells (hMSCs) on emulsion electrospun scaffold containing poly(l-lactic acid)-co-poly-(e-caprolactone), gelatin and vascular endothelial growth factor (PLCL/GV) was investigated in this study. The characterizations of the scaffold were carried out using scanning electron microscope (SEM), transmission electron microscope, water contact angle and porometer. The proliferation of hMSCs showed that 73.4 % higher cell proliferation on PLCL/GV scaffolds than that on PLCL scaffold after 20 days of cell culture. Results of 5-chloromethylfluorescein diacetate staining and SEM morphology analysis indicated that hMSCs differentiated on PLCL/GV scaffolds showed irregular morphology of cardiomyocyte phenotype compared to the typical long and thin hMSC phenotype. Immunostaining results showed the expression of alpha actinin and myosin heavy chain. Our studies identified emulsion electrospinning as a method for fabrication of core–shell fibers suitable for the differentiation of stem cells to cardiac cells, with potential application in cardiac regeneration.

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.

Cardiac tissue engineering (TE) is one of the most promising strategies to reconstruct the infarct myocardium and the major challenge involves producing a bioactive scaffold with anisotropic properties that assist in cell guidance to mimic the heart tissue. In this study, random and aligned poly(e-caprolactone)/gelatin (PG) composite nanofibrous scaffolds were electrospun to structurally mimic the oriented extracellular matrix (ECM). Morphological, chemical and mechanical properties of the electrospun PG nanofibers were evaluated by scanning electron microscopy (SEM), water contact angle, attenuated total reflectance Fourier transform infrared spectroscopy and tensile measurements. Results indicated that PG nanofibrous scaffolds possessed smaller fiber diameters (239 ± 37 nm for random fibers and 269 ± 33 nm for aligned fibers), increased hydrophilicity, and lower stiffness compared to electrospun PCL nanofibers. The aligned PG nanofibers showed anisotropic wetting characteristics and mechanical properties, which closely match the requirements of native cardiac anisotropy. Rabbit cardiomyocytes were cultured on electrospun random and aligned nanofibers to assess the biocompatibility of scaffolds, together with its potential for cell guidance. The SEM and immunocytochemical analysis showed that the aligned PG scaffold greatly promoted cell attachment and alignment because of the biological components and ordered topography of the scaffolds. Moreover, we concluded that the aligned PG nanofibrous scaffolds could be more promising substrates suitable for the regeneration of infarct myocardium and other cardiac defects. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.

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.

Myocardial infarction (MI) leads to the loss of cardiomyocytes, followed by left ventricular (LV) remodeling and cardiac dysfunction. The authors hypothesize that an elastic, biodegradable nanofibrous cardiac patch loaded with mesenchymal stem cells (MSC) could restrain LV remodeling and improve cardiac function after MI. Poly(e-caprolactone)/gelatin (PG) nanofibers were fabricated by electrospinning, and the nanofibers displayed a porous and uniform nanofibrous structure with a diameter of 244±51nm. An MI model was established by ligation of the left anterior descending coronary artery of female Sprague-Dawley rats. The PG nanofibrous patch seeded with MSC, isolated from rat bone marrow, was implanted on the epicardium of the infarcted region of the LV wall of the heart. After transplantation, the PG-cell patch restricted the expansion of the LV wall effectively and reduced the scar size, and the density of the microvessels increased. Cells within the patch were able to migrate towards the scar tissue, and promoted new blood vessel formation at the infarct site. Angiogenesis and the cardiac functions improved significantly after 4weeks of implantation. The MSC-seeded PG nanofibrous patches are demonstrated to provide sufficient mechanical support, to induce angiogenesis and to accelerate cardiac repair in a rat model of MI. The study highlights the positive impact of implantation of an MSC-seeded PG nanofibrous patch as a novel constituent for MI repair.

Myocardial infarction is the major cause of death in many industrialized nations as it leads to end-stage heart failure. Tissue engineering (TE) approaches for treatment of the infarcted tissue have gained huge attention over the recent years and research in this direction mainly aims for the optimization of a biomaterial scaffold with suitable cell source for tissue regeneration. In this regard, we fabricated completely natural polymeric scaffolds using fibrinogen and gelatin in two different weight ratios and performed cross-linking [Fib/Gel(1:4)-CL; Fib/Gel(2:3)-CL] while cross-linked fibrinogen scaffolds were used as the control. The fiber diameters of the fabricated scaffolds were obtained in the range of 150-300 nm. Chemical characterization of the scaffolds confirmed the presence of both the proteins and showed the absence of any chemical reactions between them. The tensile strength and the stiffness values of Fib/Gel(1:4)-CL matrices were found to be 0.0125 and 0.46 MPa, respectively, which were much similar to the innate properties of the native myocardium. Cell culture studies using human cardiomyocytes revealed higher cell proliferation on Fib/Gel(1:4)-CL scaffolds compared to cell proliferation on Fib/Gel(2:3)-CL scaffolds, which was even higher than the cell proliferation on cross-linked fibrinogen scaffolds. Moreover, the cardiomyocytes seeded on composite substrates expressed the typical functional cardiac proteins such as alpha-actinin, troponin I, connexin-43, and myosin heavy chain, and could be potential for application in cardiac TE.

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.

Poly(3-hexylthiophene) (P3HT) is one of the most promising photovoltaic (PV) polymers in photocurrent therapy. A novel photosensitive scaffold for skin tissue engineering was fabricated by blending P3HT with polycaprolactone (PCL) and electrospun to obtain composite PCL/P3HT nanofibers with three different weight ratios of PCL : P3HT (w/w) of 150 : 2 [PCL/P3HT(2)], 150 : 10 [PCL/P3HT(10)] and 150 : 20 [PCL/P3HT(20)]. The photosensitive properties of the blend solutions and the composite nanofibers of PCL/P3HT were investigated. The incident photon-to-electron conversion efficiencies of the PCL/P3HT(2), PCL/P3HT(10), PCL/P3HT(20) were identified as 2.0 × 10(-6), 1.6 × 10(-5) and 2.9 × 10(-5), respectively, which confirm the photosensitive ability of the P3HT-containing scaffolds. The biocompatibility of the scaffold was evaluated by culturing human dermal fibroblasts and the results showed that the proliferation of HDFs under light stimulation on PCL/P3HT(10) was 12.8%, 11.9%, and 11.6% (p ≤ 0.05) higher than the cell growth on PCL, PCL/P3HT(2) and PCL/P3HT(20), respectively. Human dermal fibroblasts cultured under light stimulation on PCL/P3HT(10) not only showed better cell proliferation but also retained cell morphology similar to the phenotype observed on tissue culture plates (control). Our experimental results suggest novel and potential application of an optimized amount of P3HT-containing scaffold, especially PCL/P3HT(10) nanofibrous scaffold in photocurrent therapy for skin regeneration.

A bioengineered construct that matches the chemical, mechanical, biological properties and extracellular matrix morphology of native tissue could be suitable as a cardiac patch for supporting the heart after myocardial infarction. The potential of utilizing a composite nanofibrous scaffold of poly(dl-lactide-co-glycolide)/gelatin (PLGA/Gel) as a biomimetic cardiac patch is studied by culturing a population of cardiomyocyte containing cells on the electrospun scaffolds. The chemical characterization and mechanical properties of the electrospun PLGA and PLGA/Gel nanofibers were studied by Fourier transform infrared spectroscopy, scanning electron microscopy and tensile measurements. The biocompatibility of the scaffolds was also studied and the cardiomyocytes seeded on PLGA/Gel nanofibers were found to express the typical functional cardiac proteins such as alpha-actinin and troponin I, showing the easy integration of cardiomyocytes on PLGA/Gel scaffolds. Our studies strengthen the application of electrospun PLGA/Gel nanofibers as a bio-mechanical support for injured myocardium and as a potential substrate for induction of endogenous cardiomyocyte proliferation, ultimately reducing the cardiac dysfunction and improving cardiac remodeling.