Showing papers in "Journal of Functional Biomaterials in 2018"
TL;DR: The self-assembly properties of poloxamers can be leveraged to encapsulate drugs using an array of processing techniques including direct solubilization, solvent displacement methods, emulsification and preparation of kinetically-frozen nanoparticles.
Abstract: Poloxamers, also known as Pluronics®, are block copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), which have an amphiphilic character and useful association and adsorption properties emanating from this. Poloxamers find use in many applications that require solubilization or stabilization of compounds and also have notable physiological properties, including low toxicity. Accordingly, poloxamers serve well as excipients for pharmaceuticals. Current challenges facing nanomedicine revolve around the transport of typically water-insoluble drugs throughout the body, followed by targeted delivery. Judicious design of drug delivery systems leads to improved bioavailability, patient compliance and therapeutic outcomes. The rich phase behavior (micelles, hydrogels, lyotropic liquid crystals, etc.) of poloxamers makes them amenable to multiple types of processing and various product forms. In this review, we first present the general solution behavior of poloxamers, focusing on their self-assembly properties. This is followed by a discussion of how the self-assembly properties of poloxamers can be leveraged to encapsulate drugs using an array of processing techniques including direct solubilization, solvent displacement methods, emulsification and preparation of kinetically-frozen nanoparticles. Finally, we conclude with a summary and perspective.
348 citations
TL;DR: Three-dimensional printing has significant potential as a fabrication method in creating scaffolds for tissue engineering, including the ability to create complex geometries, porosities, co-culture of multiple cells, and incorporate growth factors.
Abstract: Three-dimensional printing has significant potential as a fabrication method in creating scaffolds for tissue engineering. The applications of 3D printing in the field of regenerative medicine and tissue engineering are limited by the variety of biomaterials that can be used in this technology. Many researchers have developed novel biomaterials and compositions to enable their use in 3D printing methods. The advantages of fabricating scaffolds using 3D printing are numerous, including the ability to create complex geometries, porosities, co-culture of multiple cells, and incorporate growth factors. In this review, recently-developed biomaterials for different tissues are discussed. Biomaterials used in 3D printing are categorized into ceramics, polymers, and composites. Due to the nature of 3D printing methods, most of the ceramics are combined with polymers to enhance their printability. Polymer-based biomaterials are 3D printed mostly using extrusion-based printing and have a broader range of applications in regenerative medicine. The goal of tissue engineering is to fabricate functional and viable organs and, to achieve this, multiple biomaterials and fabrication methods need to be researched.
347 citations
TL;DR: A picture of the current clinical applications of bioactive glasses is provided, and six relevant challenges deserving to be tackled in the near future are depicted.
Abstract: Bioactive glasses caused a revolution in healthcare and paved the way for modern biomaterial-driven regenerative medicine. The first 45S5 glass composition, invented by Larry Hench fifty years ago, was able to bond to living bone and to stimulate osteogenesis through the release of biologically-active ions. 45S5-based glass products have been successfully implanted in millions of patients worldwide, mainly to repair bone and dental defects and, over the years, many other bioactive glass compositions have been proposed for innovative biomedical applications, such as soft tissue repair and drug delivery. The full potential of bioactive glasses seems still yet to be fulfilled, and many of today’s achievements were unthinkable when research began. As a result, the research involving bioactive glasses is highly stimulating and requires a cross-disciplinary collaboration among glass chemists, bioengineers, and clinicians. The present article provides a picture of the current clinical applications of bioactive glasses, and depicts six relevant challenges deserving to be tackled in the near future. We hope that this work can be useful to both early-stage researchers, who are moving with their first steps in the world of bioactive glasses, and experienced scientists, to stimulate discussion about future research and discover new applications for glass in medicine.
305 citations
TL;DR: Most common types of medical 3D printing technologies, including fused deposition modeling, extrusion based bioprinting, inkjet, and polyjet printing techniques, their clinical applications, different types of biomaterials currently used by researchers, and key limitations are discussed in detail.
Abstract: The success of an implant depends on the type of biomaterial used for its fabrication. An ideal implant material should be biocompatible, inert, mechanically durable, and easily moldable. The ability to build patient specific implants incorporated with bioactive drugs, cells, and proteins has made 3D printing technology revolutionary in medical and pharmaceutical fields. A vast variety of biomaterials are currently being used in medical 3D printing, including metals, ceramics, polymers, and composites. With continuous research and progress in biomaterials used in 3D printing, there has been a rapid growth in applications of 3D printing in manufacturing customized implants, prostheses, drug delivery devices, and 3D scaffolds for tissue engineering and regenerative medicine. The current review focuses on the novel biomaterials used in variety of 3D printing technologies for clinical applications. Most common types of medical 3D printing technologies, including fused deposition modeling, extrusion based bioprinting, inkjet, and polyjet printing techniques, their clinical applications, different types of biomaterials currently used by researchers, and key limitations are discussed in detail.
289 citations
TL;DR: A general overview of BGs is provided, with particular reference to their use in clinics over the last decades and the latest synthesis/processing methods, where the use of porous scaffolds is gaining growing importance thanks to the new possibilities given by technological progress extended to both manufacturing processes and functionalization techniques.
Abstract: Nowadays, bioactive glasses (BGs) are mainly used to improve and support the healing process of osseous defects deriving from traumatic events, tumor removal, congenital pathologies, implant revisions, or infections. In the past, several approaches have been proposed in the replacement of extensive bone defects, each one with its own advantages and drawbacks. As a result, the need for synthetic bone grafts is still a remarkable clinical challenge since more than 1 million bone-graft surgical operations are annually performed worldwide. Moreover, recent studies show the effectiveness of BGs in the regeneration of soft tissues, too. Often, surgical criteria do not match the engineering ones and, thus, a compromise is required for getting closer to an ideal outcome in terms of good regeneration, mechanical support, and biocompatibility in contact with living tissues. The aim of the present review is providing a general overview of BGs, with particular reference to their use in clinics over the last decades and the latest synthesis/processing methods. Recent advances in the use of BGs in tissue engineering are outlined, where the use of porous scaffolds is gaining growing importance thanks to the new possibilities given by technological progress extended to both manufacturing processes and functionalization techniques.
185 citations
TL;DR: The possible new ways to incorporate hydrophobic drugs within hydrogel structures that have been developed through research are discussed.
Abstract: Hydrogels have been shown to be very useful in the field of drug delivery due to their high biocompatibility and ability to sustain delivery. Therefore, the tuning of their properties should be the focus of study to optimise their potential. Hydrogels have been generally limited to the delivery of hydrophilic drugs. However, as many of the new drugs coming to market are hydrophobic in nature, new approaches for integrating hydrophobic drugs into hydrogels should be developed. This article discusses the possible new ways to incorporate hydrophobic drugs within hydrogel structures that have been developed through research. This review describes hydrogel-based systems for hydrophobic compound delivery included in the literature. The section covers all the main types of hydrogels, including physical hydrogels and chemical hydrogels. Additionally, reported applications of these hydrogels are described in the subsequent sections.
173 citations
TL;DR: This article reviews the emerging field of skin wound regenerative therapies with particular emphasis on PRP and the role of growth factors in the wound healing process.
Abstract: The overall increase of chronic degenerative diseases associated with ageing makes wound care a tremendous socioeconomic burden. Thus, there is a growing need to develop novel wound healing therapies to improve cutaneous wound healing. The use of regenerative therapies is becoming increasingly popular due to the low-invasive procedures needed to apply them. Platelet-rich plasma (PRP) is gaining interest due to its potential to stimulate and accelerate the wound healing process. The cytokines and growth factors forming PRP play a crucial role in the healing process. This article reviews the emerging field of skin wound regenerative therapies with particular emphasis on PRP and the role of growth factors in the wound healing process.
155 citations
TL;DR: This review summarizes some clay minerals and their derivatives for application as nanocontainer for biologically active species.
Abstract: The goal of modern research is to use environmentally preferable materials. In this context, clay minerals are emerging candidates for their bio- and ecocompatibility, low cost and natural availability. Clay minerals present different morphologies according to their layer arrangements. The use of clay minerals, especially in biomedical applications is known from ancient times and they are regaining attention in recent years. The most representative clay minerals are kaolinit, montmorillonite, sepiolites and halloysite. This review summarizes some clay minerals and their derivatives for application as nanocontainer for biologically active species.
87 citations
TL;DR: The methods to enhance osseointegration of dental implants in low quality (type-IV) bone are described in a general manner in this review.
Abstract: Nowadays, dental implants have become more common treatment for replacing missing teeth and aim to improve chewing efficiency, physical health, and esthetics. The favorable clinical performance of dental implants has been attributed to their firm osseointegration, as introduced by Branemark in 1965. Although the survival rate of dental implants over a 10-year observation has been reported to be higher than 90% in totally edentulous jaws, the clinical outcome of implant treatment is challenged in compromised (bone) conditions, as are frequently present in elderly people. The biomechanical characteristics of bone in aged patients do not offer proper stability to implants, being similar to type-IV bone (Lekholm & Zarb classification), in which a decreased clinical fixation of implants has been clearly demonstrated. However, the search for improved osseointegration has continued forward for the new evolution of modern dental implants. This represents a continuum of developments spanning more than 20 years of research on implant related-factors including surgical techniques, implant design, and surface properties. The methods to enhance osseointegration of dental implants in low quality (type-IV) bone are described in a general manner in this review.
81 citations
TL;DR: Honey possesses anti-bacterial, anti-inflammatory and other properties that are useful for wound healing and tissue regeneration and could possibly be exploited for scaffold applications in tissue healing.
Abstract: Honey possesses anti-bacterial, anti-inflammatory and other properties that are useful for wound healing and tissue regeneration. Furthermore, honey has been used for millennia in folk medicine. The misuse of antibiotics has again boosted the use of honey in regenerative medicine. The multifaceted properties of honey could possibly be exploited for scaffold applications in tissue healing.
68 citations
TL;DR: This review discusses the recent findings on the feasibility of using MGs in self-expandable stents, and shows that a metallic glass based aortic stent can be crimped without mechanical failure, and justifies the safe deployment of this stent in human descending aorta.
Abstract: Functional and mechanical properties of novel biomaterials must be carefully evaluated to guarantee long-term biocompatibility and structural integrity of implantable medical devices. Owing to the combination of metallic bonding and amorphous structure, metallic glasses (MGs) exhibit extraordinary properties superior to conventional crystalline metallic alloys, placing them at the frontier of biomaterials research. MGs have potential to improve corrosion resistance, biocompatibility, strength, and longevity of biomedical implants, and hence are promising materials for cardiovascular stent applications. Nevertheless, while functional properties and biocompatibility of MGs have been widely investigated and validated, a solid understanding of their mechanical performance during different stages in stent applications is still scarce. In this review, we provide a brief, yet comprehensive account on the general aspects of MGs regarding their formation, processing, structure, mechanical, and chemical properties. More specifically, we focus on the additive manufacturing (AM) of MGs, their outstanding high strength and resilience, and their fatigue properties. The interconnection between processing, structure and mechanical behaviour of MGs is highlighted. We further review the main categories of cardiovascular stents, the required mechanical properties of each category, and the conventional materials have been using to address these requirements. Then, we bridge between the mechanical requirements of stents, structural properties of MGs, and the corresponding stent design caveats. In particular, we discuss our recent findings on the feasibility of using MGs in self-expandable stents where our results show that a metallic glass based aortic stent can be crimped without mechanical failure. We further justify the safe deployment of this stent in human descending aorta. It is our intent with this review to inspire biodevice developers toward the realization of MG-based stents.
TL;DR: The present review overviews the information acquired through the studies on the interaction between bisphosphonate molecules and calcium phosphates and particular attention is addressed to some important recent achievements on the applications of BP functionalized calcium phosphate as biomaterials for bone substitution/repair.
Abstract: Bisphosphonates (BPs) are the most utilized drugs for the treatment of osteoporosis, and are usefully employed also for other pathologies characterized by abnormally high bone resorption, including bone metastases. Due to the great affinity of these drugs for calcium ions, calcium phosphates are ideal delivery systems for local administration of BPs to bone, which is aimed to avoid/limit the undesirable side effects of their prolonged systemic use. Direct synthesis in aqueous medium and chemisorptions from solution are the two main routes proposed to synthesize BP functionalized calcium phosphates. The present review overviews the information acquired through the studies on the interaction between bisphosphonate molecules and calcium phosphates. Moreover, particular attention is addressed to some important recent achievements on the applications of BP functionalized calcium phosphates as biomaterials for bone substitution/repair.
TL;DR: A brief survey of recent experimental progress in DNA-based single-Molecule electronics with special focus on single-molecule conductance and I–V characteristics of individual DNA molecules is given.
Abstract: Beyond being the repository of genetic information, DNA is playing an increasingly important role as a building block for molecular electronics. Its inherent structural and molecular recognition properties render it a leading candidate for molecular electronics applications. The structural stability, diversity and programmability of DNA provide overwhelming freedom for the design and fabrication of molecular-scale devices. In the past two decades DNA has therefore attracted inordinate amounts of attention in molecular electronics. This review gives a brief survey of recent experimental progress in DNA-based single-molecule electronics with special focus on single-molecule conductance and I–V characteristics of individual DNA molecules. Existing challenges and exciting future opportunities are also discussed.
TL;DR: Experimental studies have demonstrated that collagen added fibers can be efficaciously used to administrate gentamicin for 72 h without any toxic in vitro response, thus emerging as a valid candidate for the therapeutic treatment of infected wounds.
Abstract: In the current practice, the clinical use of conventional skin substitutes such as autogenous skin grafts have shown several problems, mainly with respect to limited sources and donor site morbidity. In order to overcome these limitations, the use of smart synthetic biomaterials is tremendously diffusing as skin substitutes. Indeed, engineered skin grafts or analogues frequently play an important role in the treatment of chronic skin wounds, by supporting the regeneration of newly formed tissue, and at the same time preventing infections during the long-term treatment. In this context, natural proteins such as collagen—natively present in the skin tissue—embedded in synthetic polymers (i.e., PCL) allow the development of micro-structured matrices able to mimic the functions and to structure of the surrounding extracellular matrix. Moreover, the encapsulation of drugs, such as gentamicin sulfate, also improves the bioactivity of nanofibers, due to the efficient loading and a controlled drug release towards the site of interest. Herein, we have done a preliminary investigation on the capability of gentamicin sulfate, loaded into collagen-added nanofibers, for the controlled release in local infection treatments. Experimental studies have demonstrated that collagen added fibers can be efficaciously used to administrate gentamicin for 72 h without any toxic in vitro response, thus emerging as a valid candidate for the therapeutic treatment of infected wounds.
TL;DR: Results from the current study suggest that porcine-derived bone scaffolds warrant further consideration to serve as a potential bone graft substitute for orthopaedic surgery practice.
Abstract: Background: Bone grafts are used in approximately one half of all musculoskeletal surgeries. Autograft bone is the historic gold standard but is limited in supply and its harvest imparts significant morbidity to the patient. Alternative sources of bone graft include allografts, synthetics and, less commonly, xenografts which are taken from animal species. Xenografts are available in unlimited supply from healthy animal donors with controlled biology, avoiding the risk of human disease transmission, and may satisfy current demand for bone graft products. Methods: In the current study, cancellous bone was harvested from porcine femurs and subjected to a novel decellularization protocol to derive a bone scaffold. Results: The scaffold was devoid of donor cellular material on histology and DNA sampling (p < 0.01). Microarchitectural properties important for osteoconductive potential were preserved after decellularization as shown by high resolution imaging modalities. Proteomics data demonstrated similar profiles when comparing the porcine bone scaffold against commercially available human demineralized bone matrix approved for clinical use. Conclusion: We are unaware of any porcine-derived bone graft products currently used in orthopaedic surgery practice. Results from the current study suggest that porcine-derived bone scaffolds warrant further consideration to serve as a potential bone graft substitute.
TL;DR: The options and challenges facing biomaterial selection when a scaffold has to be designed are discussed, highlighting the possibilities in the final mold the materials should assume and the most effective techniques for its fabrication depending on the target tissue, including the alternatives to ameliorate its bioactivity.
Abstract: Tissue engineering (TE) is a multidisciplinary science, which including principles from material science, biology and medicine aims to develop biological substitutes to restore damaged tissues and organs. A major challenge in TE is the choice of suitable biomaterial to fabricate a scaffold that mimics native extracellular matrix guiding resident stem cells to regenerate the functional tissue. Ideally, the biomaterial should be tailored in order that the final scaffold would be (i) biodegradable to be gradually replaced by regenerating new tissue, (ii) mechanically similar to the tissue to regenerate, (iii) porous to allow cell growth as nutrient, oxygen and waste transport and (iv) bioactive to promote cell adhesion and differentiation. With this perspective, this review discusses the options and challenges facing biomaterial selection when a scaffold has to be designed. We highlight the possibilities in the final mold the materials should assume and the most effective techniques for its fabrication depending on the target tissue, including the alternatives to ameliorate its bioactivity. Furthermore, particular attention has been given to the influence that all these aspects have on resident cells considering the frontiers of materiobiology. In addition, a focus on chitosan as a versatile biomaterial for TE scaffold fabrication has been done, highlighting its latest advances in the literature on bone, skin, cartilage and cornea TE.
TL;DR: A patient-specific drug delivery device can be custom-designed and additively manufactured in the form of an implant that can identify, trace, and dispense a drug to the vicinity of a selected target tissue as a patient- specific function of time for bodily treatment and restoration.
Abstract: The purpose of this study is to demonstrate the ability of additive manufacturing, also known as 3D printing, to produce effective drug delivery devices and implants that are both identifiable, as well as traceable. Drug delivery devices can potentially be used for drug release in the direct vicinity of target tissues or the selected medication route in a patient-specific manner as required. The identification and traceability of additively manufactured implants can be administered through radiofrequency identification systems. The focus of this study is to explore how embedded medication and sensors can be added in different additive manufacturing processes. The concept is extended to biomaterials with the help of the literature. As a result of this study, a patient-specific drug delivery device can be custom-designed and additively manufactured in the form of an implant that can identify, trace, and dispense a drug to the vicinity of a selected target tissue as a patient-specific function of time for bodily treatment and restoration.
TL;DR: This review consolidates all relevant data pertaining to novel degradable microsphere technologies for bland embolization into a single reference, and emphasizes intended use, chemical composition, degradative mechanisms, and pre-clinical safety, efficacy, and performance, while summarizing the key advantages and disadvantages.
Abstract: Considerable efforts have been placed on the development of degradable microspheres for use in transarterial embolization indications. Using the guidance of the U.S. Food and Drug Administration (FDA) special controls document for the preclinical evaluation of vascular embolization devices, this review consolidates all relevant data pertaining to novel degradable microsphere technologies for bland embolization into a single reference. This review emphasizes intended use, chemical composition, degradative mechanisms, and pre-clinical safety, efficacy, and performance, while summarizing the key advantages and disadvantages for each degradable technology that is currently under development for transarterial embolization. This review is intended to provide an inclusive reference for clinicians that may facilitate an understanding of clinical and technical concepts related to this field of interventional radiology. For materials scientists, this review highlights innovative devices and current evaluation methodologies (i.e., preclinical models), and is designed to be instructive in the development of innovative/new technologies and evaluation methodologies.
TL;DR: The combination of the two biomaterials, i.e., genipin-enhanced fibrin hydrogel and an engineered silk scaffold was a promising approach for IVD repair and was not suitable for cell cultures; however, it was highly applicable as a filler material.
Abstract: (1) Background: Intervertebral disc (IVD) repair represents a major challenge. Using functionalised biomaterials such as silk combined with enforced hydrogels might be a promising approach for disc repair. We aimed to test an IVD repair approach by combining a genipin-enhanced fibrin hydrogel with an engineered silk scaffold under complex load, after inducing an injury in a bovine whole organ IVD culture; (2) Methods: Bovine coccygeal IVDs were isolated from ~1-year-old animals within four hours post-mortem. Then, an injury in the annulus fibrosus was induced by a 2 mm biopsy punch. The repair approach consisted of genipin-enhanced fibrin hydrogel that was used to fill up the cavity. To seal the injury, a Good Manufacturing Practise (GMP)-compliant engineered silk fleece-membrane composite was applied and secured by the cross-linked hydrogel. Then, IVDs were exposed to one of three loading conditions: no load, static load and complex load in a two-degree-of-freedom bioreactor for 14 days. Followed by assessing DNA and matrix content, qPCR and histology, the injured discs were compared to an uninjured control IVD that underwent the same loading profiles. In addition, the genipin-enhanced fibrin hydrogel was further investigated with respect to cytotoxicity on human stem cells, annulus fibrosus, and nucleus pulposus cells; (3) Results: The repair was successful as no herniation could be detected for any of the three loading conditions. Disc height was not recovered by the repair DNA and matrix contents were comparable to a healthy, untreated control disc. Genipin resulted being cytotoxic in the in vitro test but did not show adverse effects when used for the organ culture model; (4) Conclusions: The current study indicated that the combination of the two biomaterials, i.e., genipin-enhanced fibrin hydrogel and an engineered silk scaffold, was a promising approach for IVD repair. Furthermore, genipin-enhanced fibrin hydrogel was not suitable for cell cultures; however, it was highly applicable as a filler material.
TL;DR: Evaluating the cytocompatibility and cytotoxicity of a new endodontic biomaterial, PulpGuard, in comparison with two other biomaterials widely used in endodentic procedures, ProRoot Mineral Trioxide Aggregate (MTA) and Biodentine, revealed a good in vitro cytOCompatibility profile and did not significantly affect the proliferation and migration rates of APCs.
Abstract: Background: The development of materials with bioregenerative properties is critically important for vital pulp therapies and regenerative endodontic procedures. The aim of this study was to evaluate the cytocompatibility and cytotoxicity of a new endodontic biomaterial, PulpGuard, in comparison with two other biomaterials widely used in endodontic procedures, ProRoot Mineral Trioxide Aggregate (MTA) and Biodentine. Methods: Apical papilla cells (APCs) were isolated from third molars with incomplete rhizogenesis from patients with orthodontic indication for dental extraction. Cultured APCs were incubated for 24, 48, or 72 h with different dilutions of eluates prepared from the three materials. Cellular viability, mobility, and proliferation were assessed in vitro using the Alamar Blue assay and a wound-healing test. The cells were also cultured in direct contact with the surface of each material. These were then analyzed via Scanning Electron Microscopy (SEM), and the surface chemical composition was determined by Energy-Dispersive Spectroscopy (EDS). Results: Cells incubated in the presence of eluates extracted from ProRoot MTA and PulpGuard presented rates of viability comparable to those of control cells; in contrast, undiluted Biodentine eluates induced a significant reduction of cellular viability. The wound-healing assay revealed that eluates from ProRoot MTA and PulpGuard allowed for unhindered cellular migration and proliferation. Cellular adhesion was observed on the surface of all materials tested. Consistent with their disclosed composition, EDS analysis found high relative abundance of calcium in Biodentine and ProRoot MTA and high abundance of silicon in PulpGuard. Significant amounts of zinc and calcium were also present in PulpGuard discs. Concerning solubility, Biodentine and ProRoot MTA presented mild weight loss after eluate extraction, while PulpGuard discs showed significant water uptake. Conclusions: PulpGuard displayed a good in vitro cytocompatibility profile and did not significantly affect the proliferation and migration rates of APCs. Cells cultured in the presence of PulpGuard eluates displayed a similar profile to those cultured with eluates from the widely used endodontic cement ProRoot MTA.
TL;DR: Evaluated the stability of PEG-albumin scaffold systems formed using PEG polymers with three different functionalized end chemistries by quantifying in vitro system swellability to determine the most promising PEG crosslinking polymer for wound healing applications.
Abstract: Chronic dermal lesions, such as pressure ulcers, are difficult to heal. Degradable tissue scaffold systems can be employed to serve as a provisional matrix for cellular ingrowth and facilitate regenerative healing during degradation. Degradable regenerative tissue scaffold matrices can be created by crosslinking albumin with functionalized poly(ethylene glycol) (PEG) polymers. The purpose of this study was to evaluate the stability of PEG-albumin scaffold systems formed using PEG polymers with three different functionalized end chemistries by quantifying in vitro system swellability to determine the most promising PEG crosslinking polymer for wound healing applications. Of the three polymers evaluated, PEG-succinimidyl glutarate (SG) exhibited consistent gelation and handling characteristics when used as the crosslinking agent with albumin. PEG-SG polymers were identified as an appropriate synthetic crosslinking moiety in a PEG-albumin scaffold system, and further in vitro and in vivo evaluation of this scaffold system is merited.
TL;DR: In vitro assessments indicated that addition of chitosan-collagen could improve cell viability and hemocompatibility and the results are promising for further development toward vascular graft application.
Abstract: Poly-L-Lactic acid (PLLA) blended with chitosan and collagen was used to fabricate a conduit for blood vessel engineering through an electrospinning process. Various concentrations of chitosan were used in the blend in order to study its effect on the morphology, chemical bond, tensile strength, burst pressure, hemocompatibility, and cell viability (cytotoxicity) of the tube.In vitro assessments indicated that addition of chitosan-collagen could improve cell viability and hemocompatibility. Best results were demonstrated by the conduit with 10% PLLA, 0.5% chitosan, and 1% collagen. Tensile strength reached 2.13 MPa and burst pressure reached 2593 mmHg, both values that are within the range value of native blood vessel. A hemolysis percentage of 1.04% and a cell viability of 86.2% were obtained, meeting the standards of high hemocompatibility and low cytotoxicity for vascular graft material. The results are promising for further development toward vascular graft application.
TL;DR: The presented approach serves as a reliable method in screening and quantifying the antimicrobial activity of polymer composite films and is a promising biomaterial that may find future application in the biomedical and packaging sector.
Abstract: Profound screening and evaluation methods for biocide-releasing polymer films are crucial for predicting applicability and therapeutic outcome of these drug delivery systems. For this purpose, we developed an agar overlay assay embedding biopolymer composite films in a seeded microbial lawn. By combining this approach with model-dependent analysis for agar diffusion, antimicrobial potency of the entrapped drug can be calculated in terms of minimum inhibitory concentrations (MICs). Thus, the topical antiseptic 4-hexylresorcinol (4-HR) was incorporated into poly(lactic-co-glycolic acid) (PLGA) films at different loadings up to 3.7 mg/cm² surface area through a solvent casting technique. The antimicrobial activity of 4-HR released from these composite films was assessed against a panel of Gram-negative and Gram-positive bacteria, yeasts and filamentous fungi by the proposed assay. All the microbial strains tested were susceptible to PLGA-4-HR films with MIC values down to 0.4% (w/w). The presented approach serves as a reliable method in screening and quantifying the antimicrobial activity of polymer composite films. Moreover, 4-HR-loaded PLGA films are a promising biomaterial that may find future application in the biomedical and packaging sector.
TL;DR: Understanding osteoclast biology and its response to the natural microarchitecture of bone are indispensable to design suitable implant interfaces and scaffolds, which will stimulate osteoclasts in ways similar to that of native bone.
Abstract: Biomaterial integration in bone depends on bone remodelling at the bone-implant interface. Optimal balance of bone resorption by osteoclasts and bone deposition by osteoblasts is crucial for successful implantation, especially in orthopaedic surgery. Most studies examined osteoblast differentiation on biomaterials, yet few research has been conducted to explore the effect of different orthopaedic implants on osteoclast development. This review covers, in detail, the biology of osteoclasts, in vitro models of osteoclasts, and modulation of osteoclast activity by different implant surfaces, bio-ceramics, and polymers. Studies show that surface topography influence osteoclastogenesis. For instance, metal implants with rough surfaces enhanced osteoclast activity, while smooth surfaces resulted in poor osteoclast differentiation. In addition, surface modification of implants with anti-osteoporotic drug further decreased osteoclast activity. In bioceramics, osteoclast development depended on different chemical compositions. Strontium-incorporated bioceramics decreased osteoclast development, whereas higher concentrations of silica enhanced osteoclast activity. Differences between natural and synthetic polymers also modulated osteoclastogenesis. Physiochemical properties of implants affect osteoclast activity. Hence, understanding osteoclast biology and its response to the natural microarchitecture of bone are indispensable to design suitable implant interfaces and scaffolds, which will stimulate osteoclasts in ways similar to that of native bone.
TL;DR: Results suggest orientation preference towards the anode, and, on average, longer neurites in the presence of the applied DC bias than with 0 V DC bias, further support the notion that polyurea-crosslinked silica aerogels is a promising material for nerve regeneration.
Abstract: Externally applied electrical stimulation (ES) has been shown to enhance the nerve regeneration process and to influence the directionality of neurite outgrowth. In addition, the physical and chemical properties of the substrate used for nerve-cell regeneration is critical in fostering regeneration. Previously, we have shown that polyurea-crosslinked silica aerogels (PCSA) exert a positive influence on the extension of neurites by PC-12 cells, a cell-line model widely used to study neurite extension and electrical excitability. In this work, we have examined how an externally applied electric field (EF) influences the extension of neurites in PC-12 cells grown on two substrates: collagen-coated dishes versus collagen-coated crosslinked silica aerogels. The externally applied direct current (DC) bias was applied in vitro using a custom-designed chamber containing polydimethysiloxane (PDMS) embedded copper electrodes to create an electric field across the substrate for the cultured PC-12 cells. Results suggest orientation preference towards the anode, and, on average, longer neurites in the presence of the applied DC bias than with 0 V DC bias. In addition, neurite length was increased in cells grown on silica-crosslinked aerogel when compared to cells grown on regular petri-dishes. These results further support the notion that PCSA is a promising material for nerve regeneration.
TL;DR: An innovative approach of alginate bioprinting based on a CaCl2 nebulizer is shown, which could be useful in generating cell-laden hydrogel constructs for e.g., drug screening or (soft) tissue engineering applications.
Abstract: Three-dimensional (3D)-bioprinting enables scientists to mimic in vivo micro-environments and to perform in vitro cell experiments under more physiological conditions than is possible with conventional two-dimensional (2D) cell culture. Cell-laden biomaterials (bioinks) are precisely processed to bioengineer tissue three-dimensionally. One primarily used matrix material is sodium alginate. This natural biopolymer provides both fine mechanical properties when gelated and high biocompatibility. Commonly, alginate is 3D bioprinted using extrusion based devices. The gelation reaction is hereby induced by a CaCl2 solution in the building chamber after material extrusion. This established technique has two main disadvantages: (1) CaCl2 can have toxic effects on the cell-laden hydrogels by oxygen diffusion limitation and (2) good printing resolution in the CaCl2 solution is hard to achieve, since the solution needs to be removed afterwards and substituted by cell culture media. Here, we show an innovative approach of alginate bioprinting based on a CaCl2 nebulizer. The device provides CaCl2 mist to the building platform inducing the gelation. The necessary amount of CaCl2 could be decreased as compared to previous gelation strategies and limitation of oxygen transfer during bioprinting can be reduced. The device was manufactured using the MJP-3D printing technique. Subsequently, its digital blueprint (CAD file) can be modified and additive manufactured easily and mounted in various extrusion bioprinters. With our approach, a concept for a more gentle 3D Bioprinting method could be shown. We demonstrated that the concept of an ultrasound-based nebulizer for CaCl2 mist generation can be used for 3D bioprinting and that the mist-induced polymerization of alginate hydrogels of different concentrations is feasible. Furthermore, different cell-laden alginate concentrations could be used: Cell spheroids (mesenchymal stem cells) and single cells (mouse fibroblasts) were successfully 3D printed yielding viable cells and stable hydrogels after 24 h cultivation. We suggest our work to show a different and novel approach on alginate bioprinting, which could be useful in generating cell-laden hydrogel constructs for e.g., drug screening or (soft) tissue engineering applications.
TL;DR: Biological properties of the inert, hydrophobic surface of PEEK can be improved with VPS titanium coating, so that the carbon/PEEK composite cage, which has great advantages in respect of biomechanical properties, can be used safely in TLIF surgery.
Abstract: The aim of this study was to assess the performance of a new vacuum plasma sprayed (VPS) titanium-coated carbon/polyetheretherketone (PEEK) cage under first use clinical conditions. Forty-two patients who underwent a one or two segment transforaminal lumbar interbody fusion (TLIF) procedure with a new Ca/PEEK composite cage between 2012 and 2016 were retrospectively identified by an electronic patient chart review. Fusion rates (using X-ray), patient’s satisfaction, and complications were followed up for two years. A total of 90.4% of the patients were pain-free and satisfied after a follow up (FU) period of 29.1 ± 9 (range 24–39) months. A mean increase of 3° in segmental lordosis in the early period (p = 0.002) returned to preoperative levels at final follow-ups. According to the Bridwell classification, the mean 24-month G1 fusion rate was calculated as 93.6% and the G2 as 6.4%. No radiolucency around the cage (G3) or clear pseudarthrosis could be seen (G4). In conclusion, biological properties of the inert, hydrophobic surface, which is the main disadvantage of PEEK, can be improved with VPS titanium coating, so that the carbon/PEEK composite cage, which has great advantages in respect of biomechanical properties, can be used safely in TLIF surgery. High fusion rates, good clinical outcome, and low implant-related complication rates without the need to use rhBMP or additional iliac bone graft can be achieved.
TL;DR: The results, taking into account the experimental conditions, show that the adsorption efficiency increases as the total charge of the adsorbent and adsorbate species decreases if both of them are positively charged.
Abstract: An experiment on the adsorption of uranium (VI) by chitosan was conducted to investigate the efficiency of chitosan as an adsorbent for U(VI). The adsorption potential of U(VI) by chitosan was investigated with ICP-MS by varying the experimental conditions such as the pH in order to obtain the optimum conditions. Adsorption dependence on the pH was confirmed, and the highest uptake of U(VI) was observed at pH 5. In addition, to scrutinize the experimental results, quantum chemistry calculations were performed. The results, taking into account the experimental conditions, show that the adsorption efficiency increases as the total charge of the adsorbent and adsorbate species decreases if both of them are positively charged. It was also found that a slight change in the adsorption geometric configuration controls the adsorption efficiency.
TL;DR: This experimental model could be an important tool for accessing how the integration of multiple biophysical and biochemical signals regulate corneal keratocyte differentiation.
Abstract: Background: Corneal stromal cells (keratocytes) are responsible for developing and maintaining normal corneal structure and transparency, and for repairing the tissue after injury. Corneal keratocytes reside between highly aligned collagen lamellae in vivo. In addition to growth factors and other soluble biochemical factors, feedback from the extracellular matrix (ECM) itself has been shown to modulate corneal keratocyte behavior. Methods: In this study, we fabricate aligned collagen substrates using a microfluidics approach and assess their impact on corneal keratocyte morphology, cytoskeletal organization, and patterning after stimulation with platelet derived growth factor (PDGF) or transforming growth factor beta 1 (TGFβ). We also use time-lapse imaging to visualize the dynamic interactions between cells and fibrillar collagen during wound repopulation following an in vitro freeze injury. Results: Significant co-alignment between keratocytes and aligned collagen fibrils was detected, and the degree of cell/ECM co-alignment further increased in the presence of PDGF or TGFβ. Freeze injury produced an area of cell death without disrupting the collagen. High magnification, time-lapse differential interference contrast (DIC) imaging allowed cell movement and subcellular interactions with the underlying collagen fibrils to be directly visualized. Conclusions: With continued development, this experimental model could be an important tool for accessing how the integration of multiple biophysical and biochemical signals regulate corneal keratocyte differentiation.
TL;DR: In this method paper, a 3D-printing procedure for CaP paste with K-carrageenan as a biological binder is described in detail, routinely performed to create porous scaffolds for bone healing.
Abstract: Critical-size bone defects are a common clinical problem. The golden standard to treat these defects is autologous bone grafting. Besides the limitations of availability and co-morbidity, autografts have to be manually adapted to fit in the defect, which might result in a sub-optimal fit and impaired healing. Scaffolds with precise dimensions can be created using 3-dimensional (3D) printing, enabling the production of patient-specific, ‘tailor-made’ bone substitutes with an exact fit. Calcium phosphate (CaP) is a popular material for bone tissue engineering due to its biocompatibility, osteoconductivity, and biodegradable properties. To enhance bone formation, a bioactive 3D-printed CaP scaffold can be created by combining the printed CaP scaffold with biological components such as growth factors and cytokines, e.g., vascular endothelial growth factor (VEGF), bone morphogenetic protein-2 (BMP-2), and interleukin-6 (IL-6). However, the 3D-printing of CaP with a biological component is challenging since production techniques often use high temperatures or aggressive chemicals, which hinders/inactivates the bioactivity of the incorporated biological components. Therefore, in our laboratory, we routinely perform extrusion-based 3D-printing with a biological binder at room temperature to create porous scaffolds for bone healing. In this method paper, we describe in detail a 3D-printing procedure for CaP paste with K-carrageenan as a biological binder.