Studies using cellular therapies, scaffolds, and tubular structured implants have been carried out with the goal to restore functional recovery after spinal cord injury (SCI). None of these therapeutic strategies, by themselves, have been shown to be sufficient to achieve complete restoration of function. To reverse the devastating effects of SCI, an interdisciplinary approach that combines materials science and engineering, stem cell biology, and neurosurgery is being carried out. We are currently investigating a scaffold that has the ability to deliver growth factors for the proliferation and differentiation of endogenous stem cells. Neural stem cells (NSCs) derived from mice are being used to assess the efficacy of the release of growth factors from the scaffold in vitro. The fabrication of the tubular implant allows a porous scaffold to be formed, which aids in the release of growth factors added to the scaffold. Full article

We find that Mycobacterium smegmatis survives spray drying and retains cell viability in accelerated temperature stress (40 °C) conditions with a success rate that increases with increasing thermal, osmotic, and nutrient-restriction stresses applied to the mycobacterium prior to spray drying. M.smegmatis that are spray dried during log growth phase, where they suffer little or no nutrient-reduction stress, survive for less than 7 days in the dry powder state at accelerated temperature stress conditions, whereas M. smegmatis that are spray dried during stationary phase, where cells do suffer nutrient reduction, survive for up to 14 days. M. smegmatis that are spray dried from stationary phase, subjected to accelerated temperature stress conditions, regrown to stationary phase, spray dried again, and resubmitted to this same process four consecutive times, display, on the fourth spray drying iteration, an approximate ten-fold increase in stability during accelerated temperature stress testing, surviving up to 105 days. Microarray tests revealed significant differences in genetic expression of M. smegmatis between log phase and stationary phase conditions, between naïve (non spray-dried) and multiply cycled dried M. smegmatis (in log and stationary phase), and between M. smegmatis in the dry powder state following a single spray drying operation and after four consecutive spray drying operations. These differences, and other phenotypical differences, point to the carotenoid biosynthetic pathway as a probable pathway contributing to bacteria survival in the spray-dried state and suggests strategies for spray drying that may lead to significantly greater room-temperature stability of mycobacteria, including mycobacterium bovis bacille Calmette-Guerin (BCG), the current TB vaccine. Full article

The objective of this study is to develop an easy and simple diffusion-controlled fabrication technique to generate the concentration gradient of biomolecules in hydrogels. Polyacrylamide (PAAm) hydrogels with a concentration gradient of type I collagen were prepared to evaluate the cell adhesion. The PAAm hydrogel was exposed to a gradient concentration of sodium hydroxide (NaOH) solution at 52 °C to generate that of carboxyl groups in the hydrogel. The carboxyl groups generated were chemically coupled with the amino groups of type I collagen to prepare the hydrogel with a concentration gradient of collagen immobilized. The attachment of L929 fibroblasts was evaluated for the collagen-immobilized hydrogel prepared. The amount gradient of carboxyl groups in the hydrogel increased with an increase in the NaOH concentration while the carboxyl groups gradient enabled to generate a gradient of collagen immobilized in the hydrogel. On the other hand, the number of fibroblasts adhered depended on the amount of collagen immobilized. These findings indicate that the adhesion behavior of cells is modified by the concentration gradient of biomolecule in the three-dimensional scaffold of cells. Full article

Biodegradable poly(ester amide) (PEA) biomaterials derived from α-amino acids, diols, and diacids are promising materials for biomedical applications such as tissue engineering and drug delivery because of their optimized properties and susceptibility for either hydrolytic or enzymatic degradation. The objective of this work was to synthesize and characterize biodegradable PEAs based on the α-amino acids L-phenylalanine and L-methionine. Four different PEAs were prepared using 1,4-butanediol, 1,6-hexanediol, and sebacic acid by interfacial polymerization. High molecular weight PEAs with narrow polydispersity indices and excellent film-forming properties were obtained. The incubation of these PEAs in PBS and chymotrypsin indicated that the polymers are biodegradable. Human coronary artery smooth muscle cells were cultured on PEA films for 48 h and the results showed a well-spread morphology. Porous 3D scaffolds fabricated from these PEAs were found to have excellent porosities indicating the utility of these polymers for vascular tissue engineering. Full article

One of the principal challenges in the field of tissue engineering and regenerative medicine is the formation of functional microvascular networks capable of sustaining tissue constructs. Complex tissues and vital organs require a means to support oxygen and nutrient transport during the development of constructs both prior to and after host integration, and current approaches have not demonstrated robust solutions to this challenge. Here, we present a technology platform encompassing the design, construction, cell seeding and functional evaluation of tissue equivalents for wound healing and other clinical applications. These tissue equivalents are comprised of biodegradable microfluidic scaffolds lined with microvascular cells and designed to replicate microenvironmental cues necessary to generate and sustain cell populations to replace dermal and/or epidermal tissues lost due to trauma or disease. Initial results demonstrate that these biodegradable microfluidic devices promote cell adherence and support basic cell functions. These systems represent a promising pathway towards highly integrated three-dimensional engineered tissue constructs for a wide range of clinical applications. Full article

High performance coatings tailored to medical devices represent a recognised approach to modulate surface properties. Plasma-deposited fluorocarbon films have been proposed as a potential stent coating. Previous studies have shown promising adhesion properties: the 35 nm-thick film sustained plastic deformation up to 25% such as induced during the clinical implantation. In this study, the compositional and morphological changes of plasma-deposited fluorocarbon films were examined during ageing in a pseudo-physiological medium, a phosphate buffer solution (PBS), by angle-resolved XPS, FT-IR data and AFM images. The evolution of the ageing process is discussed: defluorination and crosslinking yielded an oxidized protective top layer onto the films, which showed further degradation. Full article

Creating heterogeneous tissue constructs with an even cell distribution and robust mechanical strength remain important challenges to the success of in vivo tissue engineering. To address these issues, we are developing a scaffold sheet tissue engineering strategy consisting of thin (~200 μm), strong, elastic, and porous crosslinked urethane- doped polyester (CUPE) scaffold sheets that are bonded together chemically or through cell culture. Suture retention of the tissue constructs (four sheets) fabricated by the scaffold sheet tissue engineering strategy is close to the surgical requirement (1.8 N) rendering their potential for immediate implantation without a need for long cell culture times. Cell culture results using 3T3 fibroblasts show that the scaffold sheets are bonded into a tissue construct via the extracellular matrix produced by the cells after 2 weeks of in vitro cell culture. Full article

Cylindrical elastomers were prepared through the UV-initiated crosslinking of terminally acrylated, 8,000 Da star-poly(trimethylene carbonate-co-ε-caprolactone) and star-poly(trimethylene carbonate-co-D,L-lactide). These elastomers were implanted intramuscularly into the hind legs of male Wistar rats to determine the influence of the comonomer on the weight loss, tissue response, and change in mechanical properties of the elastomer. The elastomers exhibited only a mild inflammatory response that subsided after the first week; the response was greater for the stiffer D,L-lactide-containing elastomers. The elastomers exhibited weight loss and sol content changes consistent with a bulk degradation mechanism. The D,L-lactide-containing elastomers displayed a nearly zeroorder change in Young’s modulus and stress at break over the 30 week degradation time, while the ε-caprolactone-containing elastomers exhibited little change in modulus or stress at break. Full article

Our studies of amorphous calcium phosphate (ACP)-based materials over the last decade have yielded bioactive polymeric composites capable of protecting teeth from demineralization or even regenerating lost tooth mineral. The anti-cariogenic/remineralizing potential of these ACP composites originates from their propensity, when exposed to the oral environment, to release in a sustained manner sufficient levels of mineral-forming calcium and phosphate ions to promote formation of stable apatitic tooth mineral. However, the less than optimal ACP filler/resin matrix cohesion, excessive polymerization shrinkage and water sorption of these experimental materials can adversely affect their physicochemical and mechanical properties, and, ultimately, limit their lifespan. This study demonstrates the effects of chemical structure and composition of the methacrylate monomers used to form the matrix phase of composites on degree of vinyl conversion (DVC) and water sorption of both copolymers and composites and the release of mineral ions from the composites. Modification of ACP surface via introducing cations and/or polymers ab initio during filler synthesis failed to yield mechanically improved composites. However, moderate improvement in composite’s mechanical stability without compromising its remineralization potential was achieved by silanization and/or milling of ACP filler. Using ethoxylated bisphenol A dimethacrylate or urethane dimethacrylate as base monomers and adding moderate amounts of hydrophilic 2-hydroxyethyl methacrylate or its isomer ethyl-α-hydroxymethacrylate appears to be a promising route to maximize the remineralizing ability of the filler while maintaining high DVC. Exploration of the structure/composition/property relationships of ACP fillers and polymer matrices is complex but essential for achieving a better understanding of the fundamental mechanisms that govern dissolution/re-precipitation of bioactive ACP fillers, and, ultimately, the suitability of the composites for clinical evaluation. Full article

Spider silk is an interesting biomaterial for medical applications. Recently, a method for production of recombinant spider silk protein (4RepCT) that forms macroscopic fibres in physiological solution was developed. Herein, 4RepCT and Mersilk^TM (control) fibres were implanted subcutaneously in rats for seven days, without any negative systemic or local reactions. The tissue response, characterised by infiltration of macrophages and multinucleated cells, was similar with both fibres, while only the 4RepCT-fibres supported ingrowth of fibroblasts and newly formed capillaries. This in vivo study indicates that 4RepCT-fibres are well tolerated and could be used for medical applications, e.g., tissue engineering. Full article

The development of new materials for biological application requires in vitro testing of cell/surface interactions. Cell adhesion and spreading are difficult to quantify as most materials are non-transparent and transmission microscopy cannot be used. Contrast in reflection microscopy is rather poor. We propose an alternative method for the automated screening of cell attachment and spreading using backscattered electron imaging of scanning electron microscopy. The enhanced cell contrast permits study of cell/material interactions by little differences between cells and material. Full article

Synchrotron-based soft X-ray spectromicroscopy techniques are emerging as useful tools to characterize potentially biocompatible materials and to probe protein interactions with model biomaterial surfaces. Simultaneous quantitative chemical analysis of the near surface region of the candidate biomaterial, and adsorbed proteins, peptides or other biological species can be obtained at high spatial resolution via scanning transmission X-ray microscopy (STXM) and X-ray photoemission electron microscopy (X-PEEM). Both techniques use near-edge X-ray absorption fine structure (NEXAFS) spectral contrast for chemical identification and quantitation. The capabilities of STXM and X-PEEM for the analysis of biomaterials are reviewed and illustrated by three recent studies: (1) characterization of hydrophobic surfaces, including adsorption of fibrinogen (Fg) or human serum albumin (HSA) to hydrophobic polymeric thin films, (2) studies of HSA adsorption to biodegradable or potentially biocompatible polymers, and (3) studies of biomaterials under fully hydrated conditions. Other recent applications of STXM and X-PEEM to biomaterials are also reviewed. Full article

Synthetic polymeric microspheres find application in a wide range of medical applications. Among other applications, microspheres are being used as bulking agents, embolic- or drug-delivery particles. The exact composition of the spheres varies with the application and therefore a large array of materials has been used to produce microspheres. In this review, the relation between microsphere synthesis and application is discussed for a number of microspheres that are used for different treatment strategies. Full article

The principle etiology of leg pain (sciatica) from lumbar disc herniation is mechanical compression of the nerve root. Sciatica is reduced by decompression of the herniated disc, i.e., removing mechanical compression of the nerve root. Decompression surgery typically reduces sciatica more than lumbar back pain (LBP). Decompression surgery reduces mechanical compression of the nerve root. However, decompression surgery does not directly reduce sensitization of the sensory nerves in the epidural space and disc. In addition, sensory nerves in the annulus fibrosus and epidural space are not protected from topical interaction with pain mediators induced by decompression surgery. The secondary etiology of sciatica from lumbar disc herniation is sensitization of the nerve root. Sensitization of the nerve root results from a) mechanical compression, b) exposure to cellular pain mediators, and/or c) exposure to biochemical pain mediators. Although decompression surgery reduces nerve root compression, sensory nerve sensitization often persists. These observations are consistent with continued exposure of tissue in the epidural space, including the nerve root, to increased cellular and biochemical pain mediators following surgery. A potential contributor to lumbar back pain (LBP) is stimulation of sensory nerves in the annulus fibrosus by a) cellular pain mediators and/or b) biochemical pain mediators that accompany annular tears or disruption. Sensory fibers located in the outer one-third of the annulus fibrosus increase in number and depth as a result of disc herniation. The nucleus pulposus is comprised of material that can produce an autoimmune stimulation of the sensory nerves located in the annulus and epidural space leading to LBP. The sensory nerves of the annulus fibrosus and epidural space may be sensitized by topical exposure to cellular and biochemical pain mediators induced by lumbar surgery. Annulotomy or annular rupture allows the nucleus pulposus topical access to sensory nerve fibers, thereby leading to LBP. Coverage of the annulus and adjacent structures in the epidural space by absorbable viscoelastic gels appears to reduce LBP following surgery by protecting sensory fibers from cellular and biochemical pain mediators. Full article

The connective hard tissues bone and teeth are highly porous on a micrometer scale, but show high values of compression strength at a relatively low weight. The fabrication of porous materials has been actively researched and different processes have been developed that vary in preparation complexity and also in the type of porous material that they produce. Methodologies are available for determination of pore properties. The purpose of the paper is to give an overview of these methods, the role of porosity in natural porous materials and the effect of pore properties on the living tissues. The minimum pore size required to allow the ingrowth of mineralized tissue seems to be in the order of 50 µm: larger pore sizes seem to improve speed and depth of penetration of mineralized tissues into the biomaterial, but on the other hand impair the mechanical properties. The optimal pore size is therefore dependent on the application and the used material. Full article

Due to its excellent biocompatibility and mechanical properties, various different applications of polyvinyl alcohol-hydrogels (PVA-H) has been attempted in many fields. In the field of orthopedic surgery, we have been engaged for long time in research on the clinical applications of PVA-H as a artificial cartilage, and have performed many basic experiments on the mechanical properties, synthesis of PVA-H, and developed orthopedic implants using PVA-H. From these studies, many applications of artificial articular cartilage, intervertbral disc and artificial meniscus etc. have been developed. This review will present the overview of the applications and recent advances of PVA-H cartilages, and discuss clinical potential of PVA-H for orthopedics implant. Full article

Toxicity resulting from prescription drugs such as tricyclic antidepressants and cardioactive steroids, as well as drugs of abuse and exposure to environmental chemicals, represents a major need for detoxification treatments. Particles and colloids, antibody fragments (Fab), and indirect treatment methods such as macroemulsions, are currently being developed or employed as detoxification therapies. Colloids, particles, and protein fragments typically mitigate toxicity by binding to the toxin and reducing its concentration in vital organs. Indirect methods such as macroemulsions and sodium bicarbonate act directly on the affected organs, rather than the toxin. In this review, key design parameters (i.e. binding affinity, biocompatibility, pharmacokinetics) are discussed for each type of detoxification treatment. In addition, some of the latest research in each area is reviewed. Full article

Stem/progenitor cells are promising candidates for a therapy of renal failure. However, sound knowledge about implantation and regeneration is lacking. Therefore, mechanisms leading from stem/progenitor cells into tubules are under research. Renal stem/progenitor cells were isolated from neonatal rabbit kidney and mounted between layers of polyester fleece. It creates an artificial interstitium and replaces coating by extracellular matrix proteins. Tubulogenic development is induced by aldosterone. Electron microscopy illuminates growth of tubules in close vicinity to polyester fibers. Tubules contain a differentiated epithelium. The spatial extension of tubules opens a new strategy for testing morphogenic drugs and biocompatible fleece materials. Full article

Recent advances in biotechnology demonstrate that peptides and proteins are the basis of a new generation of drugs. However, the transportation of protein drugs in the body is limited by their high molecular weight, which prevents the crossing of tissue barriers, and by their short lifetime due to immuno response and enzymatic degradation. Moreover, the ability to selectively deliver drugs to target organs, tissues or cells is a major challenge in the treatment of several human diseases, including cancer. Indeed, targeted delivery can be much more efficient than systemic application, while improving bioavailability and limiting undesirable side effects. This review describes how the use of targeted nanocarriers such as nanoparticles and liposomes can improve the pharmacokinetic properties of protein drugs, thus increasing their safety and maximizing the therapeutic effect. Full article

Collagen is the most widely distributed class of proteins in the human body. The use of collagen-based biomaterials in the field of tissue engineering applications has been intensively growing over the past decades. Multiple cross-linking methods were investigated and different combinations with other biopolymers were explored in order to improve tissue function. Collagen possesses a major advantage in being biodegradable, biocompatible, easily available and highly versatile. However, since collagen is a protein, it remains difficult to sterilize without alterations to its structure. This review presents a comprehensive overview of the various applications of collagen-based biomaterials developed for tissue engineering, aimed at providing a functional material for use in regenerative medicine from the laboratory bench to the patient bedside. Full article

Parylene is a family of chemically vapour deposited polymer with material properties that are attractive for biomedicine and nanobiotechnology. Chemically inert parylene “peel-off” stencils have been demonstrated for micropatterning biomolecular arrays with high uniformity, precise spatial control down to nanoscale resolution. Such micropatterned surfaces are beneficial in engineering biosensors and biological microenvironments. A variety of substituted precursors enables direct coating of functionalised parylenes onto biomedical implants and microfluidics, providing a convenient method for designing biocompatible and bioactive surfaces. This article will review the emerging role and applications of parylene as a biomaterial for surface chemical modification and provide a future outlook. Full article

Hydrogels have many different applications in the field of regenerative medicine. Biodegradable, injectable hydrogels could be utilized as delivery systems, cell carriers, and scaffolds for tissue engineering. Injectable hydrogels are an appealing scaffold because they are structurally similar to the extracellular matrix of many tissues, can often be processed under relatively mild conditions, and may be delivered in a minimally invasive manner. This review will discuss recent advances in the field of injectable hydrogels, including both synthetic and native polymeric materials, which can be potentially used in cartilage and soft tissue engineering applications. Full article

Human vascular endothelial cells (VEC) line the vessels of the body and are critical for the maintenance of vessel integrity and trafficking of biochemical cues. They are fundamental structural elements and are central to the signaling environment. Alterations in the normal functioning of the VEC population are associated with a number of vascular disorders among which are some of the leading causes of death in both the United States and abroad. VECs attach to their underlying stromal elements through a specialization of the extracellular matrix, the basement membrane. The basement membrane provides signaling cues to the VEC through its chemical constituents, by serving as a reservoir for cytoactive factors and through its intrinsic biophysical properties. This specialized matrix is composed of a topographically rich 3D felt-like network of fibers and pores on the nano (1–100 nm) and submicron (100–1,000 nm) size scale. The basement membrane provides biophysical cues to the overlying VECs through its intrinsic topography as well as through its local compliance (relative stiffness). These biophysical cues modulate VEC adhesion, migration, proliferation, differentiation, and the cytoskeletal signaling network of the individual cells. This review focuses on the impact of biophysical cues on VEC behaviors and demonstrates the need for their consideration in future vascular studies and the design of improved prosthetics. Full article

Hydrogel nanoparticles—also referred to as polymeric nanogels or macromolecular micelles—are emerging as promising drug carriers for therapeutic applications. These nanostructures hold versatility and properties suitable for the delivery of bioactive molecules, namely of biopharmaceuticals. This article reviews the latest developments in the use of self-assembled polymeric nanogels for drug delivery applications, including small molecular weight drugs, proteins, peptides, oligosaccharides, vaccines and nucleic acids. The materials and techniques used in the development of self-assembling nanogels are also described. Full article

Advances in the extraction, purification, and characterization of keratin proteins from hair and wool fibers over the past century have led to the development of a keratin-based biomaterials platform. Like many naturally-derived biomolecules, keratins have intrinsic biological activity and biocompatibility. In addition, extracted keratins are capable of forming self-assembled structures that regulate cellular recognition and behavior. These qualities have led to the development of keratin biomaterials with applications in wound healing, drug delivery, tissue engineering, trauma and medical devices. This review discusses the history of keratin research and the advancement of keratin biomaterials for biomedical applications. Full article

Many medical conditions require surgical reconstruction of hollow organs. Tissue engineering of organs and tissues is a promising new technique without harvest site morbidity. An ideal biomaterial should be biocompatible, support tissue formation and provide adequate structural support. It should degrade gradually and provide an environment allowing for cell-cell interaction, adhesion, proliferation, migration, and differentiation. Although tissue formation is feasible, functionality has never been demonstrated. Mainly the lack of proper innervation and vascularisation are hindering contractility and normal function. In this chapter we critically review the current state of engineering hollow organs with a special focus on innervation and vascularisation. Full article

Recent developments in biomineralization have already demonstrated that nanosized particles play an important role in the formation of hard tissues of animals. Namely, the basic inorganic building blocks of bones and teeth of mammals are nanodimensional and nanocrystalline calcium orthophosphates (in the form of apatites) of a biological origin. In mammals, tens to hundreds nanocrystals of a biological apatite were found to be combined into self-assembled structures under the control of various bioorganic matrixes. In addition, the structures of both dental enamel and bones could be mimicked by an oriented aggregation of nanosized calcium orthophosphates, determined by the biomolecules. The application and prospective use of nanodimensional and nanocrystalline calcium orthophosphates for a clinical repair of damaged bones and teeth are also known. For example, a greater viability and a better proliferation of various types of cells were detected on smaller crystals of calcium orthophosphates. Thus, the nanodimensional and nanocrystalline forms of calcium orthophosphates have a great potential to revolutionize the field of hard tissue engineering starting from bone repair and augmentation to the controlled drug delivery devices. This paper reviews current state of knowledge and recent developments of this subject starting from the synthesis and characterization to biomedical and clinical applications. More to the point, this review provides possible directions of future research and development. Full article

The development of blood-compatible materials is reviewed. It grew from originally simplistic views of physical requirements such as surface charge and wettability, to endothelial cells seeded onto a biodegradable cast, and tissue engineering. In vitro findings grew from the discovery of one specific protein being adsorbed, to that of sequential protein adsorption with complex implications of platelet and white cell adhesion. The main challenge is still the production of small blood vessels (capillaries). Full article