Biomaterial Scaffolds Research Articles

A unique biomimetic modification endows polyetherketoneketone scaffold with osteoinductivity by activating cAMP/PKA signaling pathway.

Osteoinductivity of a biomaterial scaffold can notably enhance the bone healing performance. In this study, we developed a biomimetic and hierarchically porous polyetherketoneketone (PEKK) scaffold with unique osteoinductivity using a combined surface treatment strategy of a sulfonated process and a nano bone-like apatite deposition. In a beagle intramuscular model, the scaffold induced bone formation ectopically after 12-week implantation. The better bone healing ability of the scaffold than the original PEKK was also confirmed in orthotopic sites. After culturing with bone marrow–derived mesenchymal stem cells (BMSCs), the scaffold induced osteogenic differentiation of BMSCs, and the new bone formation could be mainly depending on cell signaling through adenylate cyclase 9, which activates the cyclic adenosine monophosphate/protein kinase A signaling cascade pathways. The current work reports a new osteoinductive synthetic polymeric scaffold with its detailed molecular mechanism of action for bone repair and regeneration.

Current Concepts and Methods in Tissue Interface Scaffold Fabrication.

Damage caused by disease or trauma often leads to multi-tissue damage which is both painful and expensive for the patient. Despite the common occurrence of such injuries, reconstruction can be incredibly challenging and often may focus on a single tissue, which has been damaged to a greater extent, rather than the environment as a whole. Tissue engineering offers an approach to encourage repair, replacement, and regeneration using scaffolds, biomaterials and bioactive factors. However, there are many advantages to creating a combined scaffold fabrication method approach that incorporates the treatment and regeneration of multiple tissue types simultaneously. This review provides a guide to combining multiple tissue-engineered scaffold fabrication methods to span several tissue types concurrently. Briefly, a background in the healing and composition of typical tissues targeted in scaffold fabrication is provided. Then, common tissue-engineered scaffold fabrication methods are highlighted, specifically focusing on porosity, mechanical integrity, and practicality for clinical application. Finally, an overview of commonly used scaffold biomaterials and additives is provided, and current research in combining multiple scaffold fabrication techniques is discussed. Overall, this review will serve to bridge the critical gap in knowledge pertaining to combining different fabrication methods for tissue regeneration without disrupting structural integrity and biomaterial properties.

Biomimetic Strategies for Peripheral Nerve Injury Repair: An Exploration of Microarchitecture and Cellularization.

Injuries to the nervous system present formidable challenges to scientists, clinicians, and patients. While regeneration within the central nervous system is minimal, peripheral nerves can regenerate, albeit with limitations. The regenerative mechanisms of the peripheral nervous system thus provide fertile ground for clinical and scientific advancement, and opportunities to learn fundamental lessons regarding nerve behavior in the context of regeneration, particularly the relationship of axons to their support cells and the extracellular matrix environment. However, few current interventions adequately address peripheral nerve injuries. This article aims to elucidate areas in which progress might be made toward developing better interventions, particularly using synthetic nerve grafts. The article first provides a thorough review of peripheral nerve anatomy, physiology, and the regenerative mechanisms that occur in response to injury. This is followed by a discussion of currently available interventions for peripheral nerve injuries. Promising biomaterial fabrication techniques which aim to recapitulate nerve architecture, along with approaches to enhancing these biomaterial scaffolds with growth factors and cellular components, are then described. The final section elucidates specific considerations when developing nerve grafts, including utilizing induced pluripotent stem cells, Schwann cells, nerve growth factors, and multilayered structures that mimic the architectures of the natural nerve.

Design of low elastic modulus and high strength TC4 porous scaffolds via new variable gradient strategies

• The porous scaffolds were designed via variable gradient strategies based on TPMS. • The porous scaffolds have lower elastic modulus and higher compressive strength. • Period number and variation magnitude obviously affect the compressive strength. • Variable gradient strategies can reasonably adjusting the material distribution. Low elastic modulus and high strength have always been the design goals of biomedical porous scaffolds. In this work, a series of porous scaffold models were designed via variable gradient strategies and successfully prepared using TC4 alloy and selective laser melting (SLM) technology. The results show that the porous scaffolds have lower elastic modulus and higher compressive strength compared with previous works. The compressive strength and permeability of porous scaffolds decreases with the increase of period number or the decrease of porosity variation magnitude, which is attributed to the variable gradient strategies reasonably adjusting the material distribution and aggregation degree of porous scaffolds.

Comparative study on selective laser sintering of aromatic and aliphatic thermoplastic polyurethanes: processability, microstructure, and mechanical properties

Selective laser sintering (SLS) of thermoplastic polyurethane (TPU) has attracted tremendous interest in producing prototypes and end-use parts for applications in mechanical energy absorption, biomedical scaffold, and wearable electronics because of the versatile properties of this material. This work aims to reveal the effects of the chemical structure on the SLS processability of TPU powders as well as the microstructure and mechanical properties of their SLS-printed parts. It was found that the aliphatic TPU exhibited better SLS processability and lower total porosity than the aromatic TPU because of its flexible polymer chains. In contrast, the aromatic TPU displayed higher tensile strength and mechanical energy absorption because of its rigid polymer chains and the increased intermolecular force. Pores in the SLS-printed parts were classified based on their morphological features, and their origins were investigated via X-ray computed tomography. This study provides guidance for the design, selection, and optimization of TPU powders for the SLS process according to different applications.

Electroconductive PEDOT nanoparticle integrated scaffolds for spinal cord tissue repair

BackgroundHostile environment around the lesion site following spinal cord injury (SCI) prevents the re-establishment of neuronal tracks, thus significantly limiting the regenerative capability. Electroconductive scaffolds are emerging as a promising option for SCI repair, though currently available conductive polymers such as polymer poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) present poor biofunctionality and biocompatibility, thus limiting their effective use in SCI tissue engineering (TE) treatment strategies.MethodsPEDOT NPs were synthesized via chemical oxidation polymerization in miniemulsion. The conductive PEDOT NPs were incorporated with gelatin and hyaluronic acid (HA) to create gel:HA:PEDOT-NPs scaffolds. Morphological analysis of both PEDOT NPs and scaffolds was conducted via SEM. Further characterisation included dielectric constant and permittivity variances mapped against morphological changes after crosslinking, Young’s modulus, FTIR, DLS, swelling studies, rheology, in-vitro, and in-vivo biocompatibility studies were also conducted.ResultsIncorporation of PEDOT NPs increased the conductivity of scaffolds to 8.3 × 10–4 ± 8.1 × 10–5 S/cm. The compressive modulus of the scaffold was tailored to match the native spinal cord at 1.2 ± 0.2 MPa, along with controlled porosity. Rheological studies of the hydrogel showed excellent 3D shear-thinning printing capabilities and shape fidelity post-printing. In-vitro studies showed the scaffolds are cytocompatible and an in-vivo assessment in a rat SCI lesion model shows glial fibrillary acidic protein (GFAP) upregulation not directly in contact with the lesion/implantation site, with diminished astrocyte reactivity. Decreased levels of macrophage and microglia reactivity at the implant site is also observed. This positively influences the re-establishment of signals and initiation of healing mechanisms. Observation of axon migration towards the scaffold can be attributed to immunomodulatory properties of HA in the scaffold caused by a controlled inflammatory response. HA limits astrocyte activation through its CD44 receptors and therefore limits scar formation. This allows for a superior axonal migration and growth towards the targeted implantation site through the provision of a stimulating microenvironment for regeneration.ConclusionsBased on these results, the incorporation of PEDOT NPs into Gel:HA biomaterial scaffolds enhances not only the conductive capabilities of the material, but also the provision of a healing environment around lesions in SCI. Hence, gel:HA:PEDOT-NPs scaffolds are a promising TE option for stimulating regeneration for SCI.

Study on bioactivity of SLMed variable gradient TC4 biomedical porous scaffolds with micro-arc oxidation treatment

PurposeThe purpose of this paper is to improve the bioactivity of variable gradient TC4 porous scaffolds prepared by selective laser melting (SLM) through the micro-arc oxidation (MAO) technique.Design/methodology/approachVariable gradient TC4 porous scaffolds were prepared by SLM, then treated with MAO at different oxidation voltages. The microstructure, thickness and composition of MAO coatings were characterized by scanning electron microscope (SEM), energy-dispersive spectroscopy (EDS) and X-ray diffraction. The bioactivity of the MAO coatings was tested by simulated body fluid (SBF) immersion test.FindingsSEM and EDS results show that with the increase of oxidation voltage, the content of Ca and P elements and the thickness of the MAO coatings increases. The thickness of the coating inside the scaffold is smaller than that of the outside regions. SBF immersion experiments showed that MAO-treated TC4 porous scaffolds had highest bioactivity at 440 V.Originality/valueThe variable gradient porous scaffolds were treated with MAO in the electrolyte containing Ca and P elements for the first time. The effect of oxidation voltages on the different region of porous scaffolds was studied in detail.

Evaluation of Wound Healing Effect of Curcumin Loaded OPL Carbon Nanospheres Embedded Chitosan Membranes

Biowaste-derived carbon biomaterial scaffolds are being used for wound healing and are the focus of interest. Carbon nanospheres derived from oil palm leaves without any catalysts via pyrolysis were loaded with a traditional drug curcumin. The wound healing scaffolds were fabricated on the PP non-woven fabric support using chitosan as the biopolymer matrix. Prepared carbon nanospheres and the scaffolds were characterized using ATR-IR and FESEM techniques. The wettability of scaffolds was examined to ensure the feasible moisture absorption ability, in vitro drug release profile and in vitro antibacterial activity against two strains of bacteria. The in vivo wound healing feature of scaffolds was studied by excision wound model for MRSA infected wound. Measured wound contraction percentage and the bacterial count on wounds at regular time intervals proved that, the scaffold dressed with chitosan and curcumin loaded carbon nanospheres showed an efficient reconstruction of skin through histopathological investigations.Graphical abstract

Modelling the Mechanical Properties of Hydroxyapatite Scaffolds Produced by Digital Light Processing-Based Vat Photopolymerization

Porosity is a key feature in dictating the overall performance of biomedical scaffolds, with special relevance to mechanical properties. Usually, compressive strength and elastic modulus are the main parameters used to determine the potential mechanical suitability of porous scaffolds for bone repair. However, their assessment may not be so easy from an experimental viewpoint and, especially if the porosity is high, so reliable for brittle bioceramic foams. Hence, assessing the relationship between porosity and mechanical properties based only on the constitutive parameters of the solid material is a challenging and important task to predict the scaffold performance for optimization during design. In this work, a set of equations was used to predict the compressive strength and elastic modulus of bone-like hydroxyapatite scaffolds produced by digital light processing-based vat photopolymerization (total porosity about 80 vol.%). The compressive strength was found to depend on total porosity, following a power-law approximation. The relationship between porosity and elastic modulus was well fitted by second-order power law, with relative density and computational models obtained by numerical simulations.

A novel insoluble film based on crosslinked-starch with gelatin containing ZnO-loaded halloysite nanotube and bacterial nanocellulose for wound healing applications

The Fabrication of appropriate skin wound dressing is a promising strategy to treat patients with severe skin injuries. In recent years, significant effort is invested in nanocomposite films made from natural polymers that have a lot of potential as artificial scaffolds for wound healing. Thus, the aim of this research was to produce nanocomposite film based on dialdehyde-corn starch/gelatin/bacterial nano-cellulose containing ZnO-loaded halloysite nanotubes (DAS-G/BC/ZHal) for tissue engineering applications. The synthesized films were examined for thermal stability, swelling ratio, degradation, and mechanical properties. The results revealed that by increasing the amount of BC (from 0.03 wt% to 0.12 wt%) in the films; the thermal stability improved. Also, the synthesized ZHal were incorporated into the DAS-G/BC nanocomposite films as a reinforcing filler and a good antibacterial agent with different concentrations of ZHal (3 and 5 wt%). Moreover, the produced DAS-G/BC/ZHal nanocomposite films significantly (P < 0.05) improved cell growth of NIH-3 T3 fibroblast cells and proliferation (around 150%) in the presence of BC and ZHal which revealed that these nanocomposite films are cytocompatible. The antibacterial activity was evaluated against Escherichia coli (E.Coli), and Staphylococcus aureus (S.aureus), which are the pathogens bacteria detected in wound infections. According to the obtained results, the generated films showed a suitable biomedical scaffold with excellent performance in tissue engineering applications.

The effect of polyethylene glycol on printability, physical and mechanical properties and osteogenic potential of 3D-printed poly (l-lactic acid)/polyethylene glycol scaffold for bone tissue engineering

One of the challenges in critical size bone defect repairing is the use of a porous degradable scaffold with appropriate properties to the host tissue. Nowadays, the three-dimensional (3D) printing method can produce custom and personalized scaffolds and overcome the problems of traditional methods by controlling the porosity and dimensions of biomaterial scaffolds. In this study, polylactic acid/polyethylene glycol (PLA/PEG) scaffolds were prepared with different PEG percentages (0, 5, 10, 15 and 20 wt%) by fused deposition modeling (FDM) to optimize printability and achieve suitable physico-mechanical properties and also enhance cellular behavior for bone tissue engineering and actually, this study complements previous studies. Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) were employed for chemical, morphological and thermal evaluations, respectively. It was shown that the adding of 20 wt% PEG to PLA 3D printed scaffolds reduced water contact angle (from 78.16 ± 3.27 to 60.00 ± 2.16), and increased surface wettability. The results also showed that the mechanical properties of the printed scaffolds were not significantly reduced by adding 5 and 10 wt% of PEG. The addition of PEG increased the degradability of scaffolds during immersion in phosphate buffer saline (PBS) solution for 8 weeks and PLA/PEG20 scaffold with 50.96 % had the highest rate of degradation. MTT assay showed that none of the studied scaffolds had cytotoxicity against MG-63 cells and increasing the PEG levels to 20 wt%, increased cell viability and adhesion and osteogenic differentiation. According to the obtained physical, mechanical and biological results, PLA/PEG scaffold printed by the FDM method can be an appropriate candidate for use in bone repair applications.

Nanofibrous scaffolds based on bacterial cellulose crosslinked with oxidized sucrose

In this work, oxidized sucrose (OS), which is a safe bio-based and non-toxic polyaldehyde, was used as a crosslinker in defibrillated bacterial cellulose (BC) sponges obtained by freeze-drying. For mimicking the proteins' crosslinking, BC was first modified with an aminosilane to partially replace the OH groups on the BC surface with more reactive amino groups. Further, the aminosilane-grafted bacterial cellulose (BCA) was crosslinked with OS in different concentrations and thermally cured. Functionalized bacterial celluloses showed a good thermal stability, comparable to that of unmodified cellulose and much improved mechanical properties. A threefold increase in the compression strength was obtained for the BCA scaffold after crosslinking and curing. This was correlated with the uniform pore structure emphasized by the micro-CT and SEM analyses. The OS-crosslinked BCA scaffolds were not cytotoxic and showed a porosity of around 80 %, which was almost 100 % open porosity. This study shows that the crosslinking of aminated BC scaffolds with OS allows the obtaining of 3D cellulose structures with good mechanical properties and high porosity, suitable for soft tissue engineering. The results recommend this new method as an innovative approach to obtaining biomaterial scaffolds that mimic the natural extracellular matrix.

Double – network hydrogel based on exopolysaccharides as a biomimetic extracellular matrix to augment articular cartilage regeneration

Cartilage regeneration remains a current challenge with no satisfactory strategy in surgery. Hydrogels with structurally and biochemically biomimicking characteristics have been regarded as a promising approach for the success of cartilage regeneration. Naturally sourced hydrogels from exopolysaccharides are ideal candidates for the construction of biomimetic extracellular matrix (ECM) because of their biomimetic networks, high water content, cytocompatibility, and biodegradability. Here, an approach that integrates covalent and ionic bonds in a hydrogel system is shown to form a natural polymeric hydrogel double network (DN) for promoting the adhesion and proliferation of chondrocytes and supporting the formation of matured cartilage tissue. DN hydrogels comprised of chemically crosslinked hyaluronan (HA) and physically crosslinked gellan gum (GG) were developed for potential scaffold fabrication. Compared with HA single network (SN) hydrogel and GG SN hydrogel, the obtained HA/GG DN hydrogel with Young's modulus of 28.6 kPa exhibited adequate compressive strength (208.9 kPa) and high toughness (dissipated energy 2837 J/m3) and thus can be used as a biomimetic extracellular matrix for minimal invasively repairing cartilage. In vitro studies showed that HA/GG DN hydrogel-based ECM promoted the proliferation of chondrocytes. The HA/GG DN hydrogel significantly supported the deposition of cartilage ECM-specific sulfated glycosaminoglycan and type II collagen and facilitated the formation of cartilage tissues. In a rabbit osteochondral defect model, HA/GG DN hydrogel significantly improved cartilage regeneration. The HA/GG DN hydrogel as a biomimetic ECM is a promising candidate as a biomaterial scaffold for cartilage regeneration and repair. Statement of significanceThe fabrication of a biomaterial scaffold as an artificial extracellular matrix (ECM) for cartilage regeneration remains a big challenge. In this work, we fabricated a double-network (DN) hydrogel based on hyaluronan and gellan gum (HA/GG) through a sequential chemical and physical cross-linking process. The HA/GG DN hydrogel exhibited high compressive strength, high toughness, stiffness, and good self-recovery property. The HA/GG DN hydrogel can support chondrocyte proliferation and new ECM deposition correlated with the enhanced mechanical properties, good cytocompatibility, and biodegradability. In vivo animal experiments demonstrated that this HA/GG DN hydrogel facilitates hyaline-like cartilage regeneration. These findings imply that the developed HA/GG DN hydrogel as a biomimetic ECM offers a hopeful new platform for cartilage tissue engineering.

Recent Advances in Designing Fibrous Biomaterials for the Domain of Biomedical, Clinical, and Environmental Applications.

Unique properties and potential applications of nanofibers have emerged as innovative approaches and opportunities in the biomedical, healthcare, environmental, and biosensor fields. Electrospinning and centrifugal spinning strategies have gained considerable attention among all kinds of strategies to produce nanofibers. These techniques produce nanofibers with high porosity and surface area, adequate pore architecture, and diverse chemical compositions. The extraordinary characteristics of nanofibers have unveiled new gates in nanomedicine to establish innovative fiber-based formulations for biomedical use, healthcare, and a wide range of other applications. The present review aims to provide a comprehensive overview of nanofibers and their broad range of applications, including drug delivery, biomedical scaffolds, tissue/bone-tissue engineering, dental applications, and environmental remediation in a single place. The review begins with a brief introduction followed by potential applications of nanofibers. Finally, the future perspectives and current challenges of nanofibers are demonstrated. This review will help researchers to engineer more efficient multifunctional nanofibers with improved characteristics for their effective use in broad areas. We strongly believe this review is a reader's delight and will help in dealing with the fundamental principles and applications of nanofiber-based scaffolds. This review will assist students and a broad range of scientific communities to understand the significance of nanofibers in several domains of nanotechnology, nanomedicine, biotechnology, and environmental remediation, which will set a benchmark for further research.

Combination of mesenchymal stem cells and three-dimensional collagen scaffold preserves ventricular remodeling in rat myocardial infarction model.

BACKGROUNDCardiovascular diseases are the major cause of mortality worldwide. Regeneration of the damaged myocardium remains a challenge due to mechanical constraints and limited healing ability of the adult heart tissue. Cardiac tissue engineering using biomaterial scaffolds combined with stem cells and bioactive molecules could be a highly promising approach for cardiac repair. Use of biomaterials can provide suitable microenvironment to the cells and can solve cell engraftment problems associated with cell transplantation alone. Mesenchymal stem cells (MSCs) are potential candidates in cardiac tissue engineering because of their multilineage differentiation potential and ease of isolation. Use of DNA methyl transferase inhibitor, such as zebularine, in combination with three-dimensional (3D) scaffold can promote efficient MSC differentiation into cardiac lineage, as epigenetic modifications play a fundamental role in determining cell fate and lineage specific gene expression.AIMTo investigate the role of collagen scaffold and zebularine in the differentiation of rat bone marrow (BM)-MSCs and their subsequent in vivo effects. METHODSMSCs were isolated from rat BM and characterized morphologically, immunophenotypically and by multilineage differentiation potential. MSCs were seeded in collagen scaffold and treated with 3 μmol/L zebularine in three different ways. Cytotoxicity analysis was done and cardiac differentiation was analyzed at the gene and protein levels. Treated and untreated MSC-seeded scaffolds were transplanted in the rat myocardial infarction (MI) model and cardiac function was assessed by echocardiography. Cell tracking was performed by DiI dye labeling, while regeneration and neovascularization were evaluated by histological and immunohistochemical analysis, res pectively. RESULTSMSCs were successfully isolated and seeded in collagen scaffold. Cytotoxicity analysis revealed that zebularine was not cytotoxic in any of the treatment groups. Cardiac differentiation analysis showed more pronounced results in the type 3 treatment group which was subsequently chosen for the transplantation in the in vivo MI model. Significant improvement in cardiac function was observed in the zebularine treated MSC-seeded scaffold group as compared to the MI control. Histological analysis also showed reduction in fibrotic scar, improvement in left ventricular wall thickness and preservation of ventricular remodeling in the zebularine treated MSC-seeded scaffold group. Immunohistochemical analysis revealed significant expression of cardiac proteins in DiI labeled transplanted cells and a significant increase in the number of blood vessels in the zebularine treated MSC-seeded collagen scaffold transplanted group.CONCLUSIONCombination of 3D collagen scaffold and zebularine treatment enhances cardiac differentiation potential of MSCs, improves cell engraftment at the infarcted region, reduces infarct size and improves cardiac function.

Polysaccharide nanofibers and hydrogel: A comparative evaluation on 3D cell culture and tumor reduction

Nanofibers and hydrogels are two forms of biomaterial scaffolds that have different properties and different applications. Polysaccharides have been used for the preparation of both scaffolds due to their biocompatibility and biodegradability. In this study, our main objective was to compare the tumor cell growth and tumor reduction potential of drug-loaded scaffolds. This was achieved using different methods for cell proliferation, epithelial–mesenchymal Transition studies, and biomarker expression-related assays. Anticancer drug doxorubicin was loaded to the scaffolds using adsorption and in vitro and in vivo tumor reduction was also performed. Results showed that both scaffolds supported the growth of cancer cells but did not promote epithelial-mesenchymal transition. A significant difference in drug release was observed and this may have influenced the in vivo tumor reduction. A fast release of the drug and higher tumor-reducing potential was observed for hydrogel. The studies confirmed that different types of scaffolds have different properties. Biomedical applications related to the structure can be dissimilar in different scenarios.

Two-photon polymerization for 3D biomedical scaffolds: Overview and updates.

The needs for high-resolution, well-defined and complex 3D microstructures in diverse fields call for the rapid development of novel 3D microfabrication techniques. Among those, two-photon polymerization (TPP) attracted extensive attention owing to its unique and useful characteristics. As an approach to implementing additive manufacturing, TPP has truly 3D writing ability to fabricate artificially designed constructs with arbitrary geometry. The spatial resolution of the manufactured structures via TPP can exceed the diffraction limit. The 3D structures fabricated by TPP could properly mimic the microenvironment of natural extracellular matrix, providing powerful tools for the study of cell behavior. TPP can meet the requirements of manufacturing technique for 3D scaffolds (engineering cell culture matrices) used in cytobiology, tissue engineering and regenerative medicine. In this review, we demonstrated the development in 3D microfabrication techniques and we presented an overview of the applications of TPP as an advanced manufacturing technique in complex 3D biomedical scaffolds fabrication. Given this multidisciplinary field, we discussed the perspectives of physics, materials science, chemistry, biomedicine and mechanical engineering. Additionally, we dived into the principles of tow-photon absorption (TPA) and TPP, requirements of 3D biomedical scaffolders, developed-to-date materials and chemical approaches used by TPP and manufacturing strategies based on mechanical engineering. In the end, we draw out the limitations of TPP on 3D manufacturing for now along with some prospects of its future outlook towards the fabrication of 3D biomedical scaffolds.

On mechanically recycled PLA-HAP-CS-based filaments for 3D printing of smart biomedical scaffolds

On mechanically recycled PLA-HAP-CS-based filaments for 3D printing of smart biomedical scaffolds

PEDOT: PSS promotes neurogenic commitment of neural crest-derived stem cells.

Poly (3,4-ethylendioxythiophene) polystyrene sulphonate (PEDOT:PSS) is the workhorse of organic bioelectronics and is steadily gaining interest also in tissue engineering due to the opportunity to endow traditional biomaterials for scaffolds with conductive properties. Biomaterials capable of promoting neural stem cell differentiation by application of suitable electrical stimulation protocols are highly desirable in neural tissue engineering. In this study, we evaluated the adhesion, proliferation, maintenance of neural crest stemness markers and neurogenic commitment of neural crest-derived human dental pulp stem cells (hDPSCs) cultured on PEDOT:PSS nanostructured thin films deposited either by spin coating (SC-PEDOT) or by electropolymerization (ED-PEDOT). In addition, we evaluated the immunomodulatory properties of hDPSCs on PEDOT:PSS by investigating the expression and maintenance of the Fas ligand (FasL). We found that both SC-PEDOT and ED-PEDOT thin films supported hDPSCs adhesion and proliferation; however, the number of cells on the ED-PEDOT after 1 week of culture was significantly higher than that on SC-PEDOT. To be noted, both PEDOT:PSS films did not affect the stemness phenotype of hDPSCs, as indicated by the maintenance of the neural crest markers Nestin and SOX10. Interestingly, neurogenic induction was clearly promoted on ED-PEDOT, as indicated by the strong expression of MAP-2 and —Tubulin-III as well as evident cytoskeletal reorganisation and appreciable morphology shift towards a neuronal-like shape. In addition, strong FasL expression was detected on both undifferentiated or undergoing neurogenic commitment hDPSCs, suggesting that ED-PEDOT supports the expression and maintenance of FasL under both expansion and differentiation conditions.

EP-273 Magnetic nanoparticle administration to a model of penetrating neurotrauma in vitro

Abstract Introduction/Aims Functional recovery in penetrating traumatic brain injury (pTBI) is hampered due to the lack of clinically approved regenerative therapies. Although a surgical emergency, pTBI management is largely supportive, with no targeted neuroregenerative therapies. Reactive gliotic and neuroinflammatory responses with a lack of spontaneous axonal regeneration represent a major barrier to repair. Emergent nanotechnologies including magnetic nanoparticles (MNPs) show promise to attenuate such responses through immunomodulation, with potential of delivery of neurotherapeutic molecules to lesion sites during surgical intervention. However, there is a lack of high throughput, neuropathomimetic, models for nano/biomaterial testing in experimental neurology. Our group recently showed glial cell interactions with a surgical biomaterial scaffold (DuraGen PlusTM) in a novel in vitro model of pTBI. Methods Mice cerebral cortices were extracted and cultured 8–10 days in vitro (DIV) using previous methodology (Basit et al, Mat Sci Eng C, 2021) with a modified chemical medium. At 8 DIV, a sterile pipette was used for transection of the culture simulating penetrating injury in vitro with injection of carboxymethyl dextran-coated magnetic nanoparticles and polyethylene glycol-coated magnetic nanoparticles into the lesion site. MNP-neural cell responses were evaluated using immunocytochemistry methods. Results Our model demonstrates hallmark reactive gliotic responses, immune cell infiltration and axonal transection in injury sites. We demonstrate preferential and competitive microglial uptake of delivered MNPs versus other neural cell types (p&amp;lt;0.05, n=5). Conclusion The model is adaptable to study neural cell responses to range of materials, offering high versatility for testing promising surgical neuromaterial based therapeutic interventions in experimental clinically relevant research.