Electrospinning of polysaccharides for regenerative medicine

Electrospinning techniques enable the production of continuous fibers with dimensions on the scale of nanometers from a wide range of natural and synthetic polymers. The number of recent studies regarding electrospun polysaccharides and their derivatives, which are potentially useful for regenerative medicine, is increasing dramatically. However, difficulties regarding the processibility of the polysaccharides (e.g., poor solubility and high surface tension) have limited their application. In this review, we summarize the characteristics of various polysaccharides such as alginate, cellulose, chitin, chitosan, hyaluronic acid, starch, dextran, and heparin, which are either currently being used or have potential to be used for electrospinning. The recent progress of nanofiber matrices electrospun from polysaccharides and their biomedical applications in tissue engineering, wound dressings, drug delivery, and enzyme immobilization are discussed.     

Electrohydrodynamics: A facile technique to fabricate drug delivery systems

Electrospinning and electrospraying are facile electrohydrodynamic fabrication methods that can generate drug delivery systems (DDS) through a one-step process. The nanostructured fiber and particle morphologies produced by these techniques offer tunable release kinetics applicable to diverse biomedical applications. Coaxial electrospinning/electrospraying, a relatively new technique of fabricating core-shell fibers/particles have added to the versatility of these DDS by affording a near zero-order drug release kinetics, dampening of burst release, and applicability to a wider range of bioactive agents. Controllable electrospinning/spraying of fibers and particles and subsequent drug release from these chiefly polymeric vehicles depends on well-defined solution and process parameters. The additional drug delivery capability from electrospun fibers can further enhance the material's functionality in tissue engineering applications. This review discusses the state-of-the-art of using electrohydrodynamic technique to generate nanofiber/particles as drug delivery devices.     

Bacterial biopolymers: From production to applications in biomedicine

Bacterial polymers obtained tremendous attention over the decades owing to its widespread use in biomedical applications. A better understanding on metabolic pathways and development of improved production strategies through metabolic engineering tools to synthesize tailor made polymer materials to meet their applicability in biomedicine. This review focuses on wide range of these biocompatible polymeric materials include polysaccharides, polyesters, polyamides and polyphosphates with wound healing, antioxidant, antitumor, antimicrobial activities. This review focuses on the advantages of various biomaterials to obtain controlled/sustained drug release and tissue engineering applications in biomedical field and the applications of microbial polysaccharides as drugs in pharmaceutical industry. This review describes the most prominent biomedical applications of bacterial biopolymer material as wound healing bandages, drug delivery, tissue engineering, ortho-dental applications and hydrogels. Reviews the future aspects based on economic feasibility and challenges in mass production and downstream processing of biopolymers and its tailor made synthesis to accomplish diverse applications.     

Drug-loaded electrospun materials in wound-dressing applications and in local cancer treatment

Introduction: During the last decade, the use of electrospinning for the fabrication of nanofibrous materials loaded with antibacterial agents or anticancer drugs for biomedical applications such as dressing materials for wound treatment and for local cancer treatment has evoked considerable interest. Different drugs can be easily incorporated in electrospun materials and their release profile can be controlled through changes in the fibers morphology, porosity and composition. The large specific surface area of the electrospun materials, the possibility for gradual release and site-specific local delivery of the active compounds lead to cytotoxicity decrease and enhancement of the therapeutic effect of the drugs.

Areas covered: The most recent studies on drug-loaded electrospun mats as materials for wound dressing or local cancer treatment are briefly summarized.

Expert opinion: The possibility for local drug delivery in cancer therapy using electrospun materials allows avoiding the oral or systemic drug application, thus leading to decrease in some deleterious side effects. The recent achievements in the comprehension of the electrospinning, in control over the surface chemical composition of the electrospun materials, and in diversifying the applied approaches and techniques, propound larger prospects for creating new materials for wound dressing and local cancer treatment.     

Polymeric core-shell nanoparticles for therapeutics

1. Nanobiotechnologies have recently attracted significant attention from chemists, biologists, engineers and pharmaceutical scientists. In particular, they have been widely applied to improve drug, protein/peptide and gene delivery. 2. This review presents recent advances in the field of drug, protein/peptide and gene delivery using natural and synthetic polymer nanoparticles and explains how polymeric nanoparticles are specifically designed to suit the needs for targeted delivery of small molecular drugs, proteins/peptides and genes. In addition, some of the challenges and prospects for these technologies are discussed.     

The future perspectives of natural materials for pulmonary drug delivery and lung tissue engineering

Introduction: Search for new, functional biomaterials that can be used to synergistically deliver a drug, enhance its adsorption and stimulate the post-injury recovery of tissue function, is one of the priorities in biomedicine. Currently used materials for drug delivery fail to satisfy one or more of these functionalities, thus they have limited potential and new classes of materials are urgently needed.

Areas covered: Natural materials, due to their origin, physical and chemical structure can potentially fulfill these requirements and there is already strong evidence of their usefulness in drug delivery. They are increasingly utilized in various therapeutic applications due to the obvious advantages over synthetic materials. Particularly in pulmonary drug delivery, there have been limitations in the use of synthetic materials such as polymers and lipids, leading to an increase in the use of natural and protein-based materials such as silk, keratin, elastin and collagen. Literature search in each specialized field, namely, silk, keratin and collagen was conducted, and the benefits of each material for future application in pulmonary drug delivery are highlighted.

Expert opinion: The natural materials discussed in this review have been well established in their use for other applications, yet further studies are required in the application of pulmonary drug delivery. The properties exhibited by these natural materials seem positive for their application in lung tissue engineering, which may allow for more extensive testing for validation of pulmonary drug delivery systems.     

Alginate and alginate composites for biomedical applications

Alginate is an edible heteropolysaccharide that abundantly available in the brown seaweed and the capsule of bacteria such as Azotobacter sp. and Pseudomonas sp. Owing to alginate gel forming capability, it is widely used in food, textile and paper industries; and to a lesser extent in biomedical applications as biomaterial to promote wound healing and tissue regeneration. This is evident from the rising use of alginate-based dressing for heavily exuding wound and their mass availability in the market nowadays. However, alginate also has limitation. When in contact with physiological environment, alginate could gelate into softer structure, consequently limits its potential in the soft tissue regeneration and becomes inappropriate for the usage related to load bearing body parts. To cater this problem, wide range of materials have been added to alginate structure, producing sturdy composite materials. For instance, the incorporation of adhesive peptide and natural polymer or synthetic polymer to alginate moieties creates an improved composite material, which not only possesses better mechanical properties compared to native alginate, but also grants additional healing capability and promote better tissue regeneration. In addition, drug release kinetic and cell viability can be further improved when alginate composite is used as encapsulating agent. In this review, preparation of alginate and alginate composite in various forms (fibre, bead, hydrogel, and 3D-printed matrices) used for biomedical application is described first, followed by the discussion of latest trend related to alginate composite utilization in wound dressing, drug delivery, and tissue engineering applications.     

Growth factor release from tissue engineering scaffolds.

Synthetic scaffold materials are used in tissue engineering for a variety of applications, including physical supports for the creation of functional tissues, protective gels to aid in wound healing and to encapsulate cells for localized hormone-delivery therapies. In order to encourage successful tissue growth, these scaffold materials must incorporate vital growth factors that are released to control their development. A major challenge lies in the requirement for these growth factor delivery mechanisms to mimic the in-vivo release profiles of factors produced during natural tissue morphogenesis or repair. This review highlights some of the major strategies for creating scaffold constructs reported thus far, along with the approaches taken to incorporate growth factors within the materials and the benefits of combining tissue engineering and drug delivery expertise.     

Self-assembling peptides: implications for patenting in drug delivery and tissue engineering

In this paper, a comprehensive review of recent patents concerning the molecular self-assembly of peptides, peptide amphiphiles and peptidomimetics into molecules through nanoarchitectures to hydrogels is provided. Their potential applications in the field of drug delivery and tissue engineering have been highlighted. The design rules of this rapidly growing field are centered mainly on the construction of peptides in the form of peptide amphiphiles, aromatic short peptide derivatives, all-amino acid peptide amphiphiles, lipidated peptides with single and multiple alkyl chains and peptide-based block copolymers and polymer peptide conjugates. The interest in patenting of self-assembling peptides is also driven by their type (I, II, III and IV) and their ability to form well-regulated highly-ordered structures such as β-sheets/β-hairpins, α-helices/coiled coils and to hierarchically self-organize into supra-molecular structures. The applicability of these systems in cell culture scaffolds for tissue engineering, drug and gene delivery and as templates for nanofabrication and biomineralization has inspired various groups over the globe. This resulted in development of self-assembling peptides as synthetic replacements of biological tissues, designing materials for specific medical applications, and materials for new applications such as diagnostic technologies. Furthermore, biologically derived and commercially available systems are also discussed herein along with a brief account of various awarded and pending patents in the past 10 years. An overview of the diversity of the patent applications is also provided for self-assembling systems based on nano- and/or micro-scale such as fibers, fibrils, gels, hydrogels, vesicles, particles, micelles, bilayers and scaffolds.     

Electrospun materials as potential platforms for bone tissue engineering

Nanofibrous materials produced by electrospinning processes have attracted considerable interest in tissue regeneration, including bone reconstruction. A range of novel materials and processing tools have been developed to mimic the native bone extracellular matrix for potential applications as tissue engineering scaffolds and ultimately to restore degenerated functions of the bone. Degradable polymers, bioactive inorganics and their nanocomposites/hybrids nanofibers with suitable mechanical properties and bone bioactivity for osteoblasts and progenitor/stem cells have been produced. The surface functionalization with apatite minerals and proteins/peptides as well as drug encapsulation within the nanofibers is a promising strategy for achieving therapeutic functions with nanofibrous materials. Recent attempts to endow a 3D scaffolding technique to the electrospinning regime have shown some promise for engineering 3D tissue constructs. With the improvement in knowledge and techniques of bone-targeted nanofibrous matrices, bone tissue engineering is expected to be realized in the near future.     

Molecularly imprinted drug delivery systems

Imprinted polymers are well established as molecular recognition materials but are now being increasingly considered for active biomedical applications such as drug delivery. In this review some highlights of recent research into molecularly imprinted drug delivery and controlled release systems are presented. The key factors controlling recognition and release by imprinted polymer matrices are discussed, the current limiting factors in their properties arising from the synthesis of these materials are considered, and the future prospects for imprinted polymers in drug delivery are outlined.     

Therapeutic applications of electrospun nanofibers for drug delivery systems

Electrospun nanofiber drug delivery systems have been studied using various techniques. Herein, we describe the fabrication of a drug-incorporating nanofiber. Drugs, such as proteins, peptide, antibodies, and small molecule drugs, can be loaded within or on the surface of nanofibers according to their properties. Hydrophobic drugs are directly dissolved with a polymer in an organic solvent before electrospinning. However, it is preferred to surface-immobilize bioactive molecules on nanofibers by physical absorption or chemical conjugation. Especially, chemically surface-immobilized proteins on a nanofiber mesh stimulate cell differentiation and proliferation. Using a dual electrospinning nozzle to create nanofiber sheet layers, which are stacked on top of one another, the initial burst release is reduced compared with solid nanofibers because of the layers. Furthermore, hybridization of electrospun nanofibers with nanoparticles, microspheres, and hydrogels is indirect drug loading method into the nanofibers. It is also possible to produce multi-drug delivery systems with timed programmed release.     

Nanotechnology for nanomedicine and delivery of drugs

Nanotechnology is an emerging technology seeking to exploit distinct technological advances controlling the structure of materials at a reduced dimensional scale approaching individual molecules and their aggregates or supramolecular structures. The manipulation and utilization of materials at nanoscale are expected to be critical drivers of economic growth and development in this century. In recent years, nanoscale sciences and engineering have provided new avenues for engineering materials down to molecular scale precision. The resultant materials have been demonstrated to have enhanced properties and applicability; and these materials are expected to be enabling technologies in the successful development and application of nanomedicine. Nanomedicine is defined as the monitoring, repair, construction, and control of human biological systems at the molecular level using engineered nanodevices and nanostructures. Electrospinning is a simple and cost-effective technique, capable of producing continuous fibers of various materials from polymers to ceramics. The electrospinning technique is used for the preparation of nanofibers and macroporous scaffolds intended for drug delivery and tissue engineering. These have special characteristics in terms of fabrication, porosity, variable diameters, topology and mechanical properties. This review summarizes the recent developments in utilizing nanofibers for drug delivery and tissue engineering applications.     

Drug delivery from gelatin-based systems

Introduction: Carriers for controlled drug release offer many advantages compared with conventional dosage forms. Gelatin has been investigated extensively as a drug delivery carrier, due to its properties and history of safe use in a wide range of medical applications.

Areas covered: Gelatin was shown to be versatile due to its intrinsic features that enable the design of different carrier systems, such as microparticles and nanoparticles, fibers and even hydrogels. Gelatin microparticles can serve as vehicles for cell amplification and for delivery of large bioactive molecules, whereas gelatin nanoparticles are better suited for intravenous delivery or for drug delivery to the brain. Gelatin fibers contain a high surface area-to-volume ratio, whereas gelatin hydrogels can trap molecules between the polymer’s crosslink gaps, allowing these molecules to diffuse into the blood stream. Another interesting area is the combination of tissue bioadhesive-based gelatin with controlled drug release for pain management and wound healing.

Expert opinion: The modification of gelatin and its combinations with other biomaterials have demonstrated the flexibility of these systems and can be employed for meeting the challenges of finding ideal carrier systems that enable specific, targeted and controlled release in response to demands in the body.     

Biomaterials-based nanofiber scaffold: targeted and controlled carrier for cell and drug delivery

Nanofiber scaffold formulations (diameter less than 1000?nm) were successfully used to deliver the drug/cell/gene into the body organs through different routes for an effective treatment of various diseases. Various fabrication methods like drawing, template synthesis, fiber-mesh, phase separation, fiber-bonding, self-assembly, melt-blown, and electrospinning are successfully used for fabrication of nanofibers. These formulations are widely used in various fields such as tissue engineering, drug delivery, cosmetics, as filter media, protective clothing, wound dressing, homeostatic, sensor devices, etc. The present review gives a detailed account on the need of the nanofiber scaffold formulation development along with the biomaterials and techniques implemented for fabrication of the same against innumerable diseases. At present, there is a huge extent of research being performed worldwide on all aspects of biomolecules delivery. The unique characteristics of nanofibers such as higher loading efficiency, superior mechanical performance (stiffness and tensile strength), controlled release behavior, and excellent stability helps in the delivery of plasmid DNA, large protein drugs, genetic materials, and autologous stem-cell to the target site in the future.     

Functional electrospun nanofibrous scaffolds for biomedical applications

Functional nanofibrous scaffolds produced by electrospinning have great potential in many biomedical applications, such as tissue engineering, wound dressing, enzyme immobilization and drug (gene) delivery. For a specific successful application, the chemical, physical and biological properties of electrospun scaffolds should be adjusted to match the environment by using a combination of multi-component compositions and fabrication techniques where electrospinning has often become a pivotal tool. The property of the nanofibrous scaffold can be further improved with innovative development in electrospinning processes, such as two-component electrospinning and in-situ mixing electrospinning. Post modifications of electrospun membranes also provide effective means to render the electrospun scaffolds with controlled anisotropy and porosity. In this article, we review the materials, techniques and post modification methods to functionalize electrospun nanofibrous scaffolds suitable for biomedical applications.     

Neomycin-loaded poly(styrene sulfonic acid-co-maleic acid) (PSSA-MA)/polyvinyl alcohol (PVA) ion exchange nanofibers for wound dressing materials

In this study, poly(styrene sulfonic acid-co-maleic acid) (PSSA-MA) blended with polyvinyl alcohol (PVA) was electrospun and then subjected to thermal crosslinking to produce PSSA-MA/PVA ion exchange nanofiber mats. The cationic drug neomycin (0.001, 0.01, and 0.1%, w/v) was loaded onto the cationic exchange fibers. The amount of neomycin loaded and released and the cytotoxicity of the fiber mats were analyzed. In vivo wound healing tests were also performed in Wistar rats. The results indicated that the diameters of the fibers were on the nanoscale (250 ± 21 nm). The ion exchange capacity (IEC) value and the percentage of water uptake were 2.19 ± 0.1 mequiv./g-dry fibers and 268 ± 15%, respectively. The loading capacity was increased upon increasing the neomycin concentration. An initial concentration of 0.1% (w/v) neomycin (F3) showed the highest loading capacity (65.7 mg/g-dry fibers). The neomycin-loaded nanofiber mats demonstrated satisfactory antibacterial activity against both Gram-positive and Gram-negative bacteria, and an in vivo wound healing test revealed that these mats performed better than gauze and blank nanofiber mats in decreasing acute wound size during the first week after tissue damage. In conclusion, the antibacterial neomycin-loaded PSSA-MA/PVA cationic exchange nanofiber mats have the potential for use as wound dressing materials.     

Approaches to neural tissue engineering using scaffolds for drug delivery

This review seeks to give an overview of the current approaches to drug delivery from scaffolds for neural tissue engineering applications. The challenges presented by attempting to replicate the three types of nervous tissue (brain, spinal cord, and peripheral nerve) are summarized. Potential scaffold materials (both synthetic and natural) and target drugs are discussed with the benefits and drawbacks given. Finally, common methods of drug delivery, including degradable/diffusion-based delivery systems, affinity-based delivery systems, immobilized drug delivery systems, and electrically controlled drug delivery systems, are examined and critiqued. Based on the current body of work, suggestions for future directions of research in the field of neural tissue engineering are presented.     

Controlled local drug delivery strategies from chitosan hydrogels for wound healing

Introduction: The main target of tissue engineering is the preparation and application of adequate materials for the design and production of scaffolds, that possess properties promoting cell adhesion, proliferation and differentiation. The use of natural polysaccharides, such as chitosan, to prepare hydrogels for wound healing and controlled drug delivery is a research topic of wide and increasing interest.

Areas covered: This review presents the latest results and challenges in the preparation of chitosan and chitosan-based scaffold/hydrogel for wound healing applications. A detailed overview of their behavior in terms of controlled drug delivery, divided by drug categories, and efficacy was provided and critically discussed.

Expert opinion: The need to establish and exploit the advantages of natural biomaterials in combination with active compounds is playing a pivotal role in the regenerative medicine fields. The challenges posed by the many variables affecting tissue repair and regeneration need to be standardized and adhere to recognized guidelines to improve the quality of evidence in the wound healing process. Currently, different methodologies are followed to prepare innovative scaffold formulations and structures. Innovative technologies such as 3D printing or bio-electrospray are promising to create chitosan-based scaffolds with finely controlled structures with customizable shape porosity and thickness. Chitosan scaffolds could be designed in combination with a variety of polysaccharides or active compounds with selected and reproducible spacial distribution, providing active wound dressing with highly tunable controlled drug delivery.     

Polymer Architecture and Drug Delivery

Polymers occupy a major portion of materials used for controlled release formulations and drug-targeting systems because this class of materials presents seemingly endless diversity in topology and chemistry. This is a crucial advantage over other classes of materials to meet the ever-increasing requirements of new designs of drug delivery formulations. The polymer architecture (topology) describes the shape of a single polymer molecule. Every natural, seminatural, and synthetic polymer falls into one of categorized architectures: linear, graft, branched, cross-linked, block, star-shaped, and dendron/dendrimer topology. Although this topic spans a truly broad area in polymer science, this review introduces polymer architectures along with brief synthetic approaches for pharmaceutical scientists who are not familiar with polymer science, summarizes the characteristic properties of each architecture useful for drug delivery applications, and covers recent advances in drug delivery relevant to polymer architecture.