In some traumatic nerve injuries, autologous nerve grafting is the first choice for bridging the gap between the severed nerve ends. However, this therapeutic strategy has some disadvantages, including permanent loss of donor function and requirement of multiple surgeries. An attractive alternative to this therapeutic technique is the use of artificial nerve conduit. Poly (L-lactic acid) (PLLA) is widely used as a substrate for artificial nerve conduit because it is readily biodegradable, but it is not inherently biologically active. In this study, we developed a PLLA nanofibrous nerve conduit, modified with a conjugate of oligo (D-lactic acid) (ODLA) and the neurite outgrowth, thereby promoting peptide AG73 (RKRLQVQLSIRT) to improve nerve regeneration. PLA/ODLA-AG73 nanofibrous conduit was fabricated by electrospinning and then transplanted at the 10 mm gap of rat sciatic nerve. After six months, electrophysiological evaluation revealed that it achieved better functional reinnervation than silicone tube (used as a reference) or unmodified PLLA nanofibrous conduit. Full article

The aim of this study was to investigate non-viral pDNA carriers based on diblock-copolymers consisting of poly(2-(dimethyl amino)ethyl methacrylate) (pDMAEMA) and poly(2-hydroxyethyl methacrylate) (pHEMA). Specifically the block-lengths and molecular weights were varied to determine the minimal requirements for transfection. Such vectors should allow better transfection at acceptable toxicity levels and the entire diblock-copolymer should be suitable for renal clearance. For this purpose, a library of linear poly(2-(dimethyl amino)ethyl methacrylate-block-poly(2-hydroxyl methacrylate) (pDMAEMA-block-pHEMA) copolymers was synthesized via RAFT (reversible addition-fragmentation chain transfer) polymerization in a molecular weight (Mw) range of 17–35.7 kDa and analyzed using ¹H and ¹³C NMR (nuclear magnetic resonance), ATR (attenuated total reflectance), GPC (gel permeation chromatography) and DSC (differential scanning calorimetry). Copolymers possessing short pDMAEMA-polycation chains were 1.4–9.7 times less toxic in vitro than polyethylenimine (PEI) 25 kDa, and complexed DNA into polyplexes of 100–170 nm, favorable for cellular uptake. The DNA-binding affinity and polyplex stability against competing polyanions was comparable with PEI 25 kDa. The zeta-potential of polyplexes of pDMAEMA-grafted copolymers remained positive (+15–30 mV). In comparison with earlier reported low molecular weight homo pDMAEMA vectors, these diblock-copolymers showed enhanced transfection efficacy under in vitro conditions due to their lower cytotoxicity, efficient cellular uptake and DNA packaging. The homo pDMAEMA₁₁₅ (18.3 kDa) self-assembled with DNA into small positively charged polyplexes, but was not able to transfect cells. The grafting of 6 and 57 repeating units of pHEMA (0.8 and 7.4 kDa) to pDMAEMA₁₁₅ increased the transfection efficacy significantly, implying a crucial impact of pHEMA on vector-cell interactions. The intracellular trafficking, in vivo transfection efficacy and kinetics of low molecular weight pDMAEMA-block-pHEMA are subject of ongoing studies. Full article

The development of growth factor delivery strategies to circumvent the burst release phenomenon prevalent in most current systems has driven research towards encapsulating molecules in resorbable polymer matrices. For these polymer release techniques to be efficacious in a clinical setting, several key points need to be addressed. This present study has investigated the encapsulation of the growth factor, BMP-2 within PLGA/PLGA-PEG-PLGA microparticles. Morphology, size distribution, encapsulation efficiency and release kinetics were investigated and we have demonstrated a sustained release of bioactive BMP-2. Furthermore, biocompatibility of the PLGA microparticles was established and released BMP-2 was shown to promote the differentiation of MC3T3-E1 cells towards the osteogenic lineage to a greater extent than osteogenic supplements (as early as day 10 in culture), as determined using alkaline phosphatase and alizarin red assays. This study showcases a potential BMP-2 delivery system which may now be translated into more complex delivery systems, such as 3D, mechanically robust scaffolds for bone tissue regeneration applications. Full article

Fibers that can provide topographical, biochemical and electrical cues would be attractive for directing the differentiation of stem cells into electro-responsive cells such as neuronal or muscular cells. Here we report on the fabrication of polypyrrole-incorporated collagen-based fibers via interfacial polyelectrolyte complexation (IPC). The mean ultimate tensile strength of the fibers is 304.0 ± 61.0 MPa and the Young’s Modulus is 10.4 ± 4.3 GPa. Human bone marrow-derived mesenchymal stem cells (hMSCs) are cultured on the fibers in a proliferating medium and stimulated with an external electrical pulse generator for 5 and 10 days. The effects of polypyrrole in the fiber system can be observed, with hMSCs adopting a neuronal-like morphology at day 10, and through the upregulation of neural markers, such as noggin, MAP2, neurofilament, β tubulin III and nestin. This study demonstrates the potential of this fiber system as an attractive 3D scaffold for tissue engineering, where collagen is present on the fiber surface for cellular adhesion, and polypyrrole is encapsulated within the fiber for enhanced electrical communication in cell-substrate and cell-cell interactions. Full article

We succeeded in causing transmittance self-oscillations of a novel self-oscillating polymer chain induced by the Belouzov-Zhabotinsky (BZ) reaction under constant conditions. The novel polymer chain was composed of a biocompatible and non-thermoresponsive poly-vinylpyrrolidone (PVP) main-chain, covalently-bonded to the ruthenium catalyst (Ru(bpy)₃) of the BZ reaction. We investigated the influence of initial substrate concentrations of the three BZ substrates on the transmittance self-oscillation of the novel polymer solution. As a result, we demonstrated that the width of the transmittance self-oscillation is significantly affected by these initial concentrations. However, the amplitude of the transmittance self-oscillation is hardly affected by the BZ substrate conditions. Furthermore, the period of the self‑oscillation has a good linear relationship to the concentration of the BZ substrates. Therefore, the period of the self-oscillation can be controlled by the selection of the initial concentrations of the BZ substrates. Full article

An in vitro method for the time-resolved quantification of acid-mediated tooth demineralisation has been developed and evaluated against putative non-permanent protective formulations based on a series of poly(alkyl methacrylate)s. Using a thermostatted carousel, dentally relevant substrates consisting of hydroxyapatite discs or sections of bovine teeth have been exposed to aqueous citric acid under controlled conditions, before and after being treated with the polymeric coatings. The dissolution of phosphate was monitored by the determination of ³¹P by Inductively Coupled Plasma—Mass Spectrometry and by the spectrophotometric phosphovanadomolybdate method. Dose-response plots constructed for both groups of treated substrates have revealed that the coatings significantly reduce erosion rates but are less effective at inhibiting tooth demineralisation than the standard fluoride treatment. The approach has enabled an evaluation of the erosion-protection efficiency of each coating. Full article

The ability to reproducibly load bioactive molecules into polymeric microspheres is a challenge. Traditional microsphere fabrication methods typically provide inhomogeneous release profiles and suffer from lack of batch to batch reproducibility, hindering their potential to up-scale and their translation to the clinic. This deficit in homogeneity is in part attributed to broad size distributions and variability in the morphology of particles. It is thus desirable to control morphology and size of non-loaded particles in the first instance, in preparation for obtaining desired release profiles of loaded particles in the later stage. This is achieved by identifying the key parameters involved in particle production and understanding how adapting these parameters affects the final characteristics of particles. In this study, electrospraying was presented as a promising technique for generating reproducible particles made of polycaprolactone, a biodegradable, FDA-approved polymer. Narrow size distributions were obtained by the control of electrospraying flow rate and polymer concentration, with average particle sizes ranging from 10 to 20 µm. Particles were shown to be spherical with a homogeneous embossed texture, determined by the polymer entanglement regime taking place during electrospraying. No toxic residue was detected by this process based on preliminary cell work using DNA quantification assays, validating this method as suitable for further loading of bioactive components. Full article

In the present work, the immobilization of gelatin as biopolymer on two types of implantable biomaterials, polyimide and titanium, was compared. Both materials are known for their biocompatibility while lacking cell-interactive behavior. For both materials, a pre-functionalization step was required to enable gelatin immobilization. For the polyimide foils, a reactive succinimidyl ester was introduced first on the surface, followed by covalent grafting of gelatin. For the titanium material, methacrylate groups were first introduced on the Ti surface through a silanization reaction. The applied functionalities enabled the subsequent immobilization of methacrylamide modified gelatin. Both surface modified materials were characterized in depth using atomic force microscopy, static contact angle measurements, confocal fluorescence microscopy, attenuated total reflection infrared spectroscopy and X-ray photo-electron spectroscopy. The results indicated that the strategies elaborated for both material classes are suitable to apply stable gelatin coatings. Interestingly, depending on the material class studied, not all surface analysis techniques are applicable. Full article

The nanostructure of bone has been replicated using a polymer-induced liquid-precursor (PILP) mineralization process. This polymer-mediated crystallization process yields intrafibrillar mineralization of collagen with uniaxially-oriented hydroxyapatite crystals. The process-directing agent, an anionic polymer which we propose mimics the acidic non-collagenous proteins associated with bone formation, sequesters calcium and phosphate ions to form amorphous precursor droplets that can infiltrate the interstices of collagen fibrils. In search of a polymeric agent that produces the highest mineral content in the shortest time, we have studied the influence of various acidic polymers on the in vitro mineralization of collagen scaffolds via the PILP process. Among the polymers investigated were poly-L-aspartic acid (PASP), poly-L-glutamic acid (PGLU), polyvinylphosphonic acid (PVPA), and polyacrylic acid (PAA). Our data indicate that PASP and the combination of PGLU/PASP formed stable mineralization solutions, and yielded nano-structured composites with the highest mineral content. Such studies contribute to our goal of preparing biomimetic bone graft substitutes with composition and structure that mimic bone. Full article

Statins, a group of potent inhibitors of 3-hydroxy-3-methylglutaryl Coenzyme A reductase in cholesterol biosynthesis pathway, have been widely used as a cholesterol lowering drug. The plieotrophic effect of statins on bone metabolism in long-term usage has been begun to be studied during recent years and several in vitro and in vivo studies have demonstrated the ability of statins to promote expression of bone morphogenetic protein-2 (BMP-2), inhibition of osteoclast differentiation and reduction of osteoporotic fractures risk. The high liver specificity and low oral bioavailability of statins, leading to poor peripheral distribution, are the main obstacles to benefit anabolic effects of hydrophobic statins on bone formation. Therefore, developing new administration roots for direct delivery to achieve optimum concentration in the bone microenvironment is of interest. Here we present and compare two approaches of combining statins with bone tissue engineering scaffolds. Simvastatin was combined with a poly(lactide-co-glycolide) (PLGA) membrane scaffold for diffusion-controlled release by dissolving simvastatin (dis-sim) in the membrane casting dope, and for degradation-controlled release by covalently bonding saponifiedsimvastatin (sap-sim) to the PLGA in the spinning dope. Rheological and concentration-dependent membrane morphology changes were observed with saponifiedsimvastatin, suggesting ester bond cleavage and covalent bonding of the statin to the PLGA, but not with dissolved simvastatin. Dissolved simvastatin membranes showed a logarithmic decay release profile while the saponifiedsimvastatin membranes showed constant release. It can be concluded that the covalent bonding of simvastatinto PLGA scaffolds is showing potential for use as a controlled releasescaffold for bone tissue engineering. Full article

Novel propargyl-ended heterobifunctional poly(ethylene glycol) (PEG) derivatives with hydroxyl, carboxyl, mercapto or hydrazide end groups were synthesized with simplicity yet high efficiency. PEG (M_w = 3500 Da) with an α-hydroxyl group and an ω-carboxyl was used as the starting polymer. The carboxyl group of the bifunctional PEG was modified into a propargyl, then carboxyl, mercapto or hydrazide groups were introduced to the other end of the bifunctional PEG by modifying the bifunctional PEG’s hydroxyl group with succinic anhydride, cysteamide or tert-butyl carbazate, respectively. This method can be useful to the development of PEG-based bioconjugates for a variety of biomedical applications. Full article

Cardiac tissue regeneration is an integrated process involving both cells and supporting matrix. Cardiomyocytes and stem cells are utilized to regenerate cardiac tissue. Hydrogels, because of their tissue-like properties, have been used as supporting matrices to deliver cells into infarcted cardiac muscle. Bioactive and biocompatible hydrogels mimicking biochemical and biomechanical microenvironments in native tissue are needed for successful cardiac tissue regeneration. These hydrogels not only retain cells in the infarcted area, but also provide support for restoring myocardial wall stress and cell survival and functioning. Many hydrogels, including natural polymer hydrogels, synthetic polymer hydrogels, and natural/synthetic hybrid hydrogels are employed for cardiac tissue engineering. In this review, types of hydrogels used for cardiac tissue engineering are briefly introduced. Their advantages and disadvantages are discussed. Furthermore, strategies for cardiac regeneration using hydrogels are reviewed. Full article

The goal of modern dentistry and plastic surgery is to restore the patient to normal function, health and aesthetics, regardless of the disease or injury to the stomatognathic and cutaneous system respectively. In recent years tissue engineering and regenerative medicine have yielded many novel tissue replacements and implementation strategies. Scientific advances in biomaterials, stem cell isolation, growth and differentiation factors and biomimetic environments have created unique opportunities to fabricate tissues in the laboratory. Repairing of bone and skin is likely to become of clinical interest when three dimensional tissue reconstructive procedures and the appropriate supporting biomimetic materials are correctly assembled. In the present review, we provide an overview of the most promising biopolymers that may find clinical application in dento-maxillo-facial and plastic surgery. Full article

The use of biomaterials processed by the electrospinning technique has gained considerable interest for neural tissue engineering applications. The tissue engineering strategy is to facilitate the regrowth of nerves by combining an appropriate cell type with the electrospun scaffold. Electrospinning can generate fibrous meshes having fiber diameter dimensions at the nanoscale and these fibers can be nonwoven or oriented to facilitate neurite extension via contact guidance. This article reviews studies evaluating the effect of the scaffold’s architectural features such as fiber diameter and orientation on neural cell function and neurite extension. Electrospun meshes made of natural polymers, proteins and compositions having electrical activity in order to enhance neural cell function are also discussed. Full article

Bacterial infection from medical devices is a major problem and accounts for an increasing number of deaths as well as high medical costs. Many different strategies have been developed to decrease the incidence of medical device related infection. One way to prevent infection is by modifying the surface of the devices in such a way that no bacterial adhesion can occur. This requires modification of the complete surface with, mostly, hydrophilic polymeric surface coatings. These materials are designed to be non-fouling, meaning that protein adsorption and subsequent microbial adhesion are minimized. Incorporation of antimicrobial agents in the bulk material or as a surface coating has been considered a viable alternative for systemic application of antibiotics. However, the manifestation of more and more multi-drug resistant bacterial strains restrains the use of antibiotics in a preventive strategy. The application of silver nanoparticles on the surface of medical devices has been used to prevent bacterial adhesion and subsequent biofilm formation. The nanoparticles are either deposited directly on the device surface, or applied in a polymeric surface coating. The silver is slowly released from the surface, thereby killing the bacteria present near the surface. In the last decade there has been a surplus of studies applying the concept of silver nanoparticles as an antimicrobial agent on a range of different medical devices. The main problem however is that the exact antimicrobial mechanism of silver remains unclear. Additionally, the antimicrobial efficacy of silver on medical devices varies to a great extent. Here we will review existing antimicrobial coating strategies and discuss the use of silver or silver nanoparticles on surfaces that are designed to prevent medical device related infections. Full article

In this paper, we introduce autonomous gel actuators driven by chemical energy. The polymer gels prepared here have cyclic chemical reaction networks. With a cyclic reaction, the polymer gels generate periodical motion. The periodic motion of the gel is produced by the chemical energy of the oscillatory Belouzov-Zhabotinsky (BZ) reaction. We have succeeded in making synthetic polymer gel move autonomously like a living organism. This experimental fact represents the great possibility of the chemical robot. Full article

Transport of drugs applied by traditional dosage forms is restricted to the eye, and therapeutic drug concentrations in the target tissues are not maintained for a long duration since the eyes are protected by a unique anatomy and physiology. For the treatment of the anterior segment of the eye, various droppable products to prolong the retention time on the ocular surface have been introduced in the market. On the other hand, direct intravitreal implants, using biodegradable or non-biodegradable polymer technology, have been widely investigated for the treatment of chronic vitreoretinal diseases. There is urgent need to develop ocular drug delivery systems which provide controlled release for the treatment of chronic diseases, and increase patient’s and doctor’s convenience to reduce the dosing frequency and invasive treatment. In this article, progress of ocular drug delivery systems under clinical trials and in late experimental stage is reviewed. Full article

Today, demand exists for new systems that can meet the challenges of identifying biological entities rapidly and specifically in diagnostics, developing stable and multifunctional membranes, and engineering devices at the nanometer scale. In this respect, bio-decorated membranes combine the specificity and efficacy of biological entities, such as peptides, proteins, and DNA, with stability and the opportunity to chemically tailor the properties of polymeric membranes. A smart strategy that serves to fulfill biological criteria is required, whereby polymer membranes come to mimic biological membranes and do not disturb but rather enhance the functioning and activity of a biological entity. Different approaches have been developed, exemplified by either planar or vesicular membranes, allowing insertion inside the polymer membrane or anchoring via functionalization of the membrane surface. Inspired by nature, but incorporating the strength provided by chemical design, bio-decorated polymer membranes represent a novel concept with great potential in diagnostics and therapeutics. Full article

Poly(ester amide)s are an emerging group of biodegradable polymers that may cover both commodity and speciality applications. These polymers have ester and amide groups on their chemical structure which are of a degradable character and provide good thermal and mechanical properties. In this sense, the strong hydrogen‑bonding interactions between amide groups may counter some typical weaknesses of aliphatic polyesters like for example poly(e-caprolactone). Poly(ester amide)s can be prepared from different monomers and following different synthetic methodologies which lead to polymers with random, blocky and ordered microstructures. Properties like hydrophilic/hydrophobic ratio and biodegradability can easily be tuned. During the last decade a great effort has been made to get functionalized poly(ester amide)s by incorporation of a-amino acids with hydroxyl, carboxyl and amine pendant groups and also by incorporation of carbon-carbon double bonds in both the polymer main chain and the side groups. Specific applications of these materials in the biomedical field are just being developed and are reviewed in this work (e.g., controlled drug delivery systems, hydrogels, tissue engineering and other uses like adhesives and smart materials) together with the main families of functionalized poly(ester amide)s that have been developed to date. Full article

Procedures for the treatment of retinal detachment and related conditions have been successfully improved upon in recent years thanks to the advent of new therapies and biomaterials. This review, after giving an overview on eye structure and function, focuses on the treatment of retinal detachment and examines the role and features of the materials used in vitreoretinal surgery, emphasizing scleral buckling and short-term/long-term vitreous tamponade. Specifically, the limitations of existing biomaterials are underlined, based on experimental studies and with particular reference to cells/material interactions. Finally, current and future trends of biomaterials’ research in the field of vitreoretinal surgery are considered and discussed. Full article

In this study, we succeeded in manufacturing a novel nanofiber hydrogel actuator that caused a bending and stretching motion synchronized with external pH oscillation, based on a bromate/sulfite/ferrocyanide reaction. The novel nanofiber gel actuator was composed of electrospun nanofibers synthesized by copolymerizing acrylic acid and hydrophobic butyl methacrylate as a solubility control site. By changing the electrospinning flow rate, the nanofiber gel actuator introduced an anisotropic internal structure into the gel. Therefore, the unsymmetrical motion of the nanofiber actuator was generated. Full article