Abstract Introduction Intracanal disinfection is a crucial step in regenerative endodontic procedures. Most published cases suggest the use of sodium hypochlorite (NaOCl) as the primary irrigant. ...However, the effect of clinically used concentrations of NaOCl on the survival and differentiation of stem cells is largely unknown. In this study, we tested the effect of various concentrations of NaOCl on the stem cells of the apical papilla (SCAPs) survival and dentin sialophosphoprotein (DSPP) expression. Methods Standardized root canals were created in extracted human teeth and irrigated with NaOCl (0.5%, 1.5%, 3%, or 6%) followed by 17% EDTA or sterile saline. SCAPs in a hyaluronic acid–based scaffold were seeded into the canals and cultured for 7 days. Next, viable cells were quantified using a luminescence assay, and DSPP expression was evaluated using quantitative real-time polymerase chain reaction. Results There was a significant reduction in survival and DSPP expression in the group treated with 6% NaOCl compared with the untreated control group. Comparable survival was observed in the groups treated with the lower concentrations of NaOCl, but greater DSPP expression was observed in the 1.5% NaOCl group. In addition, 17% EDTA resulted in increased survival and DSPP expression partially reversing the deleterious effects of NaOCl. Conclusions Collectively, the results suggest that dentin conditioning with high concentrations of NaOCl has a profound negative effect on the survival and differentiation of SCAPs. However, this effect can be prevented with the use of 1.5% NaOCl followed by 17% EDTA. The inclusion of this irrigation regimen might be beneficial in regenerative endodontic procedures.
Conducting polymers in biomedical engineering Guimard, Nathalie K.; Gomez, Natalia; Schmidt, Christine E.
Progress in polymer science,
08/2007, Volume:
32, Issue:
8
Journal Article
Peer reviewed
Conducting polymers (CPs) were first produced in the mid-1970s as a novel generation of organic materials that have both electrical and optical properties similar to those of metals and inorganic ...semiconductors, but which also exhibit the attractive properties associated with conventional polymers, such as ease of synthesis and flexibility in processing. The fact that several tissues are responsive to electrical fields and stimuli has made CPs attractive for a number of biological and medical applications. This review provides information on desirable CP properties specific to biomedical applications and how CPs have been optimized to generate these properties. The manuscript first introduces different types of CPs, their unique properties and their synthesis. Then specific information is provided on their modification for use in applications such as biosensors, tissue engineering, and neural probes. Although there remain many unanswered questions, particularly regarding the mechanisms by which electrical conduction through CPs affects cells, there is already compelling evidence to demonstrate the significant impact that CPs are starting to make in the biomedical field.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Biomedical engineers are at the forefront of developing novel treatments to improve human health, however, many products fail to translate to clinical implementation. In vivo pre-clinical animal ...models, although the current best approximation of complex disease conditions, are limited by reproducibility, ethical concerns, and poor accurate prediction of human response. Hence, there is a need to develop physiologically relevant, low cost, scalable, and reproducible in vitro platforms to provide reliable means for testing drugs, biomaterials, and tissue engineered products for successful clinical translation. One emerging approach of developing physiologically relevant in vitro models utilizes decellularized tissues/organs as biomaterial platforms for 2D and 3D models of healthy and diseased tissue. Decellularization is a process that removes cellular content and produces tissue-specific extracellular matrix scaffolds that can more accurately recapitulate an organ/tissue's native microenvironment compared to other natural or synthetic materials. Decellularized tissues hold enormous potential for in vitro modeling of various disease phenotypes and tissue responses to drugs or external conditions such as aging, toxin exposure, or even implantation. In this review, we highlight the need for in vitro models, the advantages and limitations of implementing decellularized tissues, and considerations of the decellularization process. We discuss current research efforts towards applying decellularized tissues as platforms to generate in vitro models of healthy and diseased tissues, and where we foresee the field progressing. A variety of organs/tissues are discussed, including brain, heart, kidney, large intestine, liver, lung, skeletal muscle, skin, and tongue.
Many biomedical products fail to reach clinical translation due to animal model limitations. Development of physiologically relevant in vitro models can provide a more economic, scalable, and reproducible means of testing drugs/therapeutics for successful clinical translation. The use of decellularized tissues as platforms for in vitro models holds promise, as these scaffolds can effectively replicate native tissue complexity, but is not widely explored. This review discusses the need for in vitro models, the promise of decellularized tissues as biomaterial substrates, and the current research applying decellularized tissues towards the creation of in vitro models. Further, this review provides insights into the current limitations and future of such in vitro models.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hyaluronic acid (HA) is ubiquitously found in biological tissues and mediates wound healing mechanisms after injury by promoting cell migration and proliferation. With the development of ...tissue-engineered neural therapeutics, including off-the-shelf grafts for peripheral nerve repair, HA is an attractive material for clinical use because of its various biological roles. HA-based biomaterials have been carefully engineered to elicit specific in vivo host responses, however an important design feature that should be considered in these scaffolds is endogenous degradation. Hyaluronidases (HYALs) are the complementary enzymes that are responsible for HA turnover. Although HYAL expression has been widely characterized in various tissues, including the central nervous system, and for different pathologies, there remains a lack of knowledge of HYAL mediated turnover in peripheral nerve tissue. In this work, gene expression of two hyaluronidases, HYAL1 and HYAL2, and HA-binding receptor, CD44, were studied in two injury models: rat sciatic nerve crush and critical gap transection. HYAL2 and CD44 were shown to be upregulated 3 days after crush injury, whereas HYAL1 was upregulated at 3 weeks, which collectively demonstrate temporal patterning of HA breakdown. Additionally, differences were observed between HYAL and HA expression at 3 weeks when compared for both nerve injury models. The activity of HYAL in peripheral nerve tissue was determined to be approximately 0.11 mumol/min, which could be used to further model HA-based biomaterial breakdown for peripheral nerve applications. Overall, this work provides a landscape of HA turnover in peripheral nerve that can be used for future neural applications.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Schwann cell (SC) transplantation has been comprehensively studied as a strategy for spinal cord injury (SCI) repair. SCs are neuroprotective and promote axon regeneration and myelination. ...Nonetheless, substantial SC death occurs post-implantation, which limits therapeutic efficacy. The use of extracellular matrix (ECM)-derived matrices, such as Matrigel, supports transplanted SC survival and axon growth, resulting in improved motor function. Because appropriate matrices are needed for clinical translation, we test here the use of an acellular injectable peripheral nerve (iPN) matrix. Implantation of SCs in iPN into a contusion lesion did not alter immune cell infiltration compared to injury only controls. iPN implants were larger and contained twice as many SC-myelinated axons as Matrigel grafts. SC/iPN animals performed as well as the SC/Matrigel group in the BBB locomotor test, and made fewer errors on the grid walk at 4 weeks, equalizing at 8 weeks. The fact that this clinically relevant iPN matrix is immunologically tolerated and supports SC survival and axon growth within the graft offers a highly translational possibility for improving efficacy of SC treatment after SCI. To our knowledge, it is the first time that an injectable PN matrix is being evaluated to improve the efficacy of SC transplantation in SCI repair.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Carbon-based conductive and electroactive materials (e.g., derivatives of graphene, fullerenes, polypyrrole, polythiophene, polyaniline) have been studied since the 1970s for use in a broad range of ...applications. These materials have electrical properties comparable to those of commonly used metals, while providing other benefits such as flexibility in processing and modification with biologics (e.g., cells, biomolecules), to yield electroactive materials with biomimetic mechanical and chemical properties. In this review, we focus on the uses of these electroconductive materials in the context of the central and peripheral nervous system, specifically recent studies in the peripheral nerve, spinal cord, brain, eye, and ear. We also highlight in vivo studies and clinical trials, as well as a snapshot of emerging classes of electroconductive materials (e.g., biodegradable materials). We believe such specialized electrically conductive biomaterials will clinically impact the field of tissue regeneration in the foreseeable future.
This review addresses the use of conductive and electroactive materials for neural tissue regeneration, which is of significant interest to a broad readership, and of particular relevance to the growing community of scientists, engineers and clinicians in academia and industry who develop novel medical devices for tissue engineering and regenerative medicine. The review covers the materials that may be employed (primarily focusing on derivatives of fullerenes, graphene and conjugated polymers) and techniques used to analyze materials composed thereof, followed by sections on the application of these materials to nervous tissues (i.e., peripheral nerve, spinal cord, brain, optical, and auditory tissues) throughout the body.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Spinal cord injury (SCI) is a devastating and complicated condition with no cure available. The initial mechanical trauma is followed by a secondary injury characterized by inflammatory cell ...infiltration and inhibitory glial scar formation. Due to the limitations posed by the blood–spinal cord barrier, systemic delivery of therapeutics is challenging. Recent development of various nanoscale strategies provides exciting and promising new means of treating SCI by crossing the blood–spinal cord barrier and delivering therapeutics. As such, we discuss different nanomaterial fabrication methods and provide an overview of recent studies where nanomaterials were developed to modulate inflammatory signals, target inhibitory factors in the lesion, and promote axonal regeneration after SCI. We also review emerging areas of research such as optogenetics, immunotherapy and CRISPR-mediated genome editing where nanomaterials can provide synergistic effects in developing novel SCI therapy regimens, as well as current efforts and barriers to clinical translation of nanomaterials.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Neuron-targeted electrical modulation Otto, Kevin J; Schmidt, Christine E
Science (American Association for the Advancement of Science),
03/2020, Volume:
367, Issue:
6484
Journal Article
Peer reviewed
Engineering neurons to make conductive polymers enables cell type–specific behaviors
Conductive polymers have been widely studied and used for biomedical applications—including as biosensors, neural ...prostheses, and bioactuators—and for drug delivery and tissue engineering (
1
). Conductive polymers are organic chains of alternating single and double bonds, which endow the polymers with metal-like semiconductive properties. Exogenous application of electrical stimulation to these polymers can promote cellular activities such as proliferation, adhesion, migration, differentiation, and protein secretion. Because many cells and tissues, particularly neurons, are responsive to electrical fields, conductive polymers are attractive for biological and medical applications. On page 1372 of this issue, Liu
et al.
(
2
) report a genetically targeted approach to assemble conductive polymers in neurons. This in turn remodels membrane electrical properties and enables cell type–specific cellular and behavioral modulation, such as control of neuronal firing, as demonstrated in cultures of rat hippocampal neurons, mouse brain slices, human cortical spheroids, and in living
Caenorhabditis elegans
worms.
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