Biomedical Materials Research Research Articles

A Bibliometric Analysis and Visualisation of Research Trends in Health Issues of Nickel-Implants

Nickel toxicity is one of the major challenges of Nickel-based implants. The bibliometric analysis had been conducted to understand the active authors, organizations, journals, and countries involved in the research domain of “Health issues of Nickel-implants”. All published articles related to “Health Issues of Nickel-implants” from “Scopus”, were analyzed using the VOS viewer to develop analysis tables and visualization maps. This article had set the objective to consolidate the scientific literature regarding “Health Issues of Nickel-implants” and also to find out the trends related to the same. The most active journal in this research domain was the Journal of Biomedical Materials Research. The most active country was the United States of America. The leading organization engaged in the research regarding allergy of Nickel-implants was the Rush University Medical Center of United States of America. The most active authors who had made valuable contributions related to the toxicity of Nickel implants were Hallab N.J and Savarino I

A Bibliometric Analysis of the Global Trend of Using Alginate, Gelatine, and Hydroxyapatite for Bone Tissue Regeneration Applications.

Collecting information from previous investigations and expressing it in a scientometrics study can be a priceless guide to getting a complete overview of a specific research area. The aim of this study is to explore the interrelated connection between alginate, gelatine, and hydroxyapatite within the scope of bone tissue and scaffold. A review of traditional literature with data mining procedures using bibliometric analyses was considered to identify the evolution of the selected research area between 2009 and 2019. Bibliometric methods and knowledge visualization technologies were implemented to investigate diverse publications based on the following indicators: year of publication, document type, language, country, institution, author, journal, keyword, and number of citations. An analysis using a bibliometric study found that 7446 papers were located with the keywords “bone tissue” and “scaffold”, and 1767 (alginate), 185 (gelatine), 5658 (hydroxyapatite) papers with those specific sub keywords. The number of publications that relate to “tissue engineering” and bone more than doubled between 2009 (1352) and 2019 (2839). China, the United States and India are the most productive countries, while Sichuan University and the Chinese Academy of Science from China are the most important institutions related to bone tissue scaffold. Materials Science and Engineering C is the most productive journal, followed by the Journal of Biomedical Materials Research Part A. This paper is a starting point, providing the first bibliometric analysis study of bone tissue and scaffold considering alginate, gelatine and hydroxyapatite. A bibliometric analysis would greatly assist in giving a scientific insight to support desired future research work, not only associated with bone tissue engineering applications. It is expected that the analysis of alginate, gelatine and hydroxyapatite in terms of 3D bioprinting, clinical outcomes, scaffold architecture, and the regenerative medicine approach will enhance the research into bone tissue engineering in the near future. Continued studies into these research fields are highly recommended.

Passing the torch of the Journal of Biomedical Materials Research—Part A

The field of biomaterials science is a constant wonder, with the advent or application of new chemistries; novel methods to characterize biomaterials in unprecedented resolution; and exciting applications of existing, composite, or innovative biomaterials to biomedical problems. The journal will continue to publish original contributions concerning studies of the preparation, performance, and evaluation of biomaterials and the response of blood and tissues to biomaterials. In addition, interdisciplinary areas are covered, such as tissue engineering, medical devices, and controlled release technology where biomaterials play a significant role. We welcome high-quality submissions by investigators throughout the world who are making exciting advancements in these areas. The journal will also continue to publish award-winning papers selected annually by SFB, as well as timely and critical review articles. Over the last several years, the publication landscape for biomaterials research has grown substantially and provides many opportunities to publish one's work. Such decisions are made for many reasons, including the publication process, perceptions of journal impact, alignment with a professional society, turnaround time for decision, ability to effectively reach one's target audience, and visibility of the work. As the official journal of the SFB, I aim to ensure that JBMR Part A is at the top of every author's list when considering where to submit their best work. We can accomplish this by (a) identifying, inviting, and accepting high quality work; (b) publishing articles that are of wide interest; and (c) increasing the visibility and contributions of accepted articles. We have identified a collection of new Associate Editors, representing the breadth of research within our discipline. Along with myself, these individuals will be tasked with managing the review process closely in order to ensure the quality and rigor of submissions and accelerate our time to first decision. It is my goal that all submissions to the journal receive a first decision in less than 1 month. Furthermore, we have empowered Associate Editors to personally solicit submissions at scientific meetings and to also reach decisions based on their own evaluation of submissions. We need to continue striving to decrease turnaround time, increase diversity of submissions, and ensure that only high-quality papers are published. It is imperative that we accelerate publication if we are to elevate the journal to the highest level. In addition, we will use social media and other platforms to highlight the publication of new work in the journal and amplify its reach throughout the community. I will regularly evaluate the composition of our Editorial Board to ensure its involvement in our mission. Participation on our Editorial Board is an honor and recognition of great accomplishments in our discipline, and I will leverage this expertise in several ways. I will call upon the Board for advice and suggestions to continually improve all aspects of the journal. Members of the Board will be asked to evaluate papers in a timely manner. Emerging initiatives will include a reviewer mentoring program to provide personal training on best practices for reviewing papers in the journal, where trainees will be selected and matched with members of the Board. This will provide an opportunity to enhance reviewer expertise and build a connection between trainees and the journal as a preferred target for submitting manuscripts. These initiatives will empower the Board to have a lasting, positive influence on the future of the journal. Such a venture requires the participation of many individuals. Our publisher Wiley is continually working to streamline the submission process to make the submission of your manuscript faster and more efficient. Our Associate Editors and Editorial Board work hard in this largely volunteer effort because of their commitment to our discipline. Our scientific community should submit our best work to JBMR Part A and say “yes” when asked to serve as reviewers. Your reviews should be thoughtful, accurate, and returned in a timely manner to improve the quality of the work and shorten the review time. We must continue to improve the quality of work published in our journal through critical discussions at annual meetings, effective reviews of submitted papers, and referencing papers from our journal in other publications. I look forward to representing our societies and discipline in this important role and partnering with Wiley Publishing to expand the reach of our journal around the globe. It is an exciting time in our field. Please embrace the JBMR Part A and help us reach the heights that our journal deserves. Onward and upward! Kent

Graphene Hybrid Materials for Controlling Cellular Microenvironments.

Cellular microenvironments are known as key factors controlling various cell functions, including adhesion, growth, migration, differentiation, and apoptosis. Many materials, including proteins, polymers, and metal hybrid composites, are reportedly effective in regulating cellular microenvironments, mostly via reshaping and manipulating cell morphologies, which ultimately affect cytoskeletal dynamics and related genetic behaviors. Recently, graphene and its derivatives have emerged as promising materials in biomedical research owing to their biocompatible properties as well as unique physicochemical characteristics. In this review, we will highlight and discuss recent studies reporting the regulation of the cellular microenvironment, with particular focus on the use of graphene derivatives or graphene hybrid materials to effectively control stem cell differentiation and cancer cell functions and behaviors. We hope that this review will accelerate research on the use of graphene derivatives to regulate various cellular microenvironments, which will ultimately be useful for both cancer therapy and stem cell-based regenerative medicine.

TomoPress—In Situ Synchrotron-Based Microtomography under Axial Load

Computed tomography (CT) with hard X-rays is a mature technique that is in regular use to depict the interior of opaque specimens with spatial resolutions up to the micrometre range (microtomography or µCT). Short acquisition times and sophisticated contrast modes are accessible when synchrotron light sources are combined with microtomography—SR-µCT. Both features render SR-µCT as excellent probe to study delicate samples in situ, for example under mechanical load by deploying corresponding sample environments. The so-called TomoPress is such a device available within the public user programme of tomography beamline ID19 of the European Synchrotron Radiation Facility (ESRF). It allows one to study samples under high axial load (up to 500 N) with high spatial resolution up to the micrometer range. Different gauges are installed to allow online monitoring of the applied force. Constant humidity, temperature and wetting are routinely available as well. The article shall outline basic design principles of the press as well as parameters for its utilisation in a descriptive manner. Selected examples underline the potential of the device for such diverse fields as biomedical research, life sciences and materials research.

Engineering of Aerogel-Based Biomaterials for Biomedical Applications.

Biomaterials with porous structure and high surface area attract growing interest in biomedical research and applications. Aerogel-based biomaterials, as highly porous materials that are made from different sources of macromolecules, inorganic materials, and composites, mimic the structures of the biological extracellular matrix (ECM), which is a three-dimensional network of natural macromolecules (e.g., collagen and glycoproteins), and provide structural support and exert biochemical effects to surrounding cells in tissues. In recent years, the higher requirements on biomaterials significantly promote the design and development of aerogel-based biomaterials with high biocompatibility and biological activity. These biomaterials with multilevel hierarchical structures display excellent biological functions by promoting cell adhesion, proliferation, and differentiation, which are critical for biomedical applications. This review highlights and discusses the recent progress in the preparation of aerogel-based biomaterials and their biomedical applications, including wound healing, bone regeneration, and drug delivery. Moreover, the current review provides different strategies for modulating the biological performance of aerogel-based biomaterials and further sheds light on the current status of these materials in biomedical research.

A study of bio and tribo modifier on degradation of magnesium-calcium carbonate biomaterial

Magnesium is emerging as a promising material in biomedical research, especially in the field of orthopedics. However, its potential to be used as an implant is little explored due to its rapid degradation. The stupendous advantage of its innate similarity in properties to that of bones is yet to be exploited. This paper aims at presenting the degradation and tribological properties of Mg-AZ91D calcium carbonate composite with WS2 and hBN as a tribo modifier. A plot of mass loss due to immersion of the composite in simulated body fluid held at 37℃ in addition to wear and coefficient of friction of the composite was discussed. Due to poor interfacial strength, the Mg composite experiences rapid mass loss initially followed by stabilization. Tribo analysis reveals a high wear resistance of the composite than the Mg alloy. The improved wear characteristics of developed biocomposite materials are widely expected to usage in an orthopedic bio implant.

Multimodal porogen platforms for calcium phosphate cement degradation.

Calcium phosphate cements (CPCs) represent excellent bone substitute materials due to their biocompatibility and injectability. However, their poor degradability and lack of macroporosity limits bone regeneration. The addition of poly(d,l‐lactic‐co‐glycolic acid) (PLGA) particles improves macroporosity and therefore late stage material degradation. CPC degradation and hence, bone formation at an early stage remains challenging, due to the delayed onset of PLGA degradation (i.e., after 2–3 weeks). Consequently, we here explored multimodal porogen platforms based on sucrose porogens (for early pore formation) and PLGA porogens (for late pore formation) to enhance CPC degradation and analyzed mechanical properties, dynamic in vitro degradation and in vivo performance in a rat femoral bone defect model. Porogen addition to CPC showed to decrease compressive strength of all CPC formulations; transition of the crystal phase upon in vitro incubation increased compressive strength. Although dynamic in vitro degradation showed rapid sucrose dissolution within 1 week, no additional effects on CPC degradation or bone formation were observed upon in vivo implantation. © 2019 The Authors. journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1713–1722, 2019.

The Evaluation of Formation and Bioactivity of New Sol-gel Bioactive Glass

In this paper, three ceramic compositions 50SiO2-50CaO (A), 45SiO2-45CaO-10P2O5 (B) and 40SiO2-40CaO-20P2O5 (C) (wt %) were synthesized by using the sol-gel technique. XRD analysis demonstrates that only sample C can form the glass material. Treated temperatures and heated times were also evaluated. Analysis data showed that the bioglass 40SiO2-40CaO-20P2O5 (wt %) can successfully elaborate when the ceramic powder heated at 750 oC for 3 hours. ‘‘In vitro’’ experiment was effectuated to investigate the bioactivity of bioglass 40SiO2-40CaO-20P2O5 by soaking powder samples in SBF solution. Obtained result confirmed the formation of hydroxyapatite (HA) phase on glass’s surface after 15 days of immersion, in which HA formation orients following (211) and (222) miller planes in crystalline structure of HA phase.
 Keywords
 Sol-gel; bioglass; hydroxyapatite; SBF; bioactivity
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Influence of processing parameters on mechanical properties of a 3D-printed trabecular bone microstructure.

Natural bone microstructure has shown to be the most efficient choice for the bone scaffold design. However, there are several process parameters involved in the generation of a microCT‐based 3D‐printed (3DP) bone. In this study, the effect of selected parameters on the reproducibility of mechanical properties of a 3DP trabecular bone structure is investigated. MicroCT images of a distal radial sample were used to reconstruct a 3D ROI of trabecular bone. Nine tensile tests on bulk material and 54 compression tests on 8.2 mm cubic samples were performed (9 cases × 6 specimens/case). The effect of input‐image resolution, STL mesh decimation, boundary condition, support material, and repetition parameters on the weight, elastic modulus, and strength were studied. The elastic modulus and the strength of bulk material showed consistent results (CV% = 9 and 6%, respectively). The weight, elastic modulus, and strength of the cubic samples showed small intragroup variation (average CV% = 1.2, 9, and 5.5%, respectively). All studied parameters had a significant effect on the outcome variables with less effect on the weight. Utmost care to every step of the 3DP process and involved parameters is required to be able to reach the desired mechanical properties in the final printed specimen. © 2019 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:38–47, 2020.

Photopolymerizable gelatin and hyaluronic acid for stereolithographic 3D bioprinting of tissue-engineered cartilage.

To create artificial cartilage in vitro, mimicking the function of native extracellular matrix (ECM) and morphological cartilage‐like shape is essential. The interplay of cell patterning and matrix concentration has high impact on the phenotype and viability of the printed cells. To advance the capabilities of cartilage bioprinting, we investigated different ECMs to create an in vitro chondrocyte niche. Therefore, we used methacrylated gelatin (GelMA) and methacrylated hyaluronic acid (HAMA) in a stereolithographic bioprinting approach. Both materials have been shown to support cartilage ECM formation and recovery of chondrocyte phenotype. We used these materials as bioinks to create cartilage models with varying chondrocyte densities. The models maintained shape, viability, and homogenous cell distribution over 14 days in culture. Chondrogenic differentiation was demonstrated by cartilage‐typical proteoglycan and type II collagen deposition and gene expression (COL2A1, ACAN) after 14 days of culture. The differentiation pattern was influenced by cell density. A high cell density print (25 × 106 cells/mL) led to enhanced cartilage‐typical zonal segmentation compared to cultures with lower cell density (5 × 106 cells/mL). Compared to HAMA, GelMA resulted in a higher expression of COL1A1, typical for a more premature chondrocyte phenotype. Both bioinks are feasible for printing in vitro cartilage with varying differentiation patterns and ECM organization depending on starting cell density and chosen bioink. The presented technique could find application in the creation of cartilage models and in the treatment of articular cartilage defects using autologous material and adjusting the bioprinted constructs size and shape to the patient. © 2019 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2649–2657, 2019.

Polylactic-co-glycolic acid microspheres added to fixative cements and its role on bone infected architecture.

Joint prostheses are an essential element to improve quality of life. However, prostheses may fail due to several factors, including the most frequent cause, Staphylococcus aureus infection. The identification of new fixing bone cements with less reactivity on bone tissue and an adequate response to infection remains a primary challenge. The aim of this study is to evaluate the response of bone tissue in rabbits after introduction of a hydroxyapatite‐coated titanium rod with a commercial fixative cement (Palacos®) compared to a modified experimental cement (EC) containing polylactic‐co‐glycolic acid (PLGA) microspheres in the presence or absence of contaminating germs. This study used 20 New Zealand rabbits which were divided into four groups (n = 5) depending on the presence or absence of S. aureus and the use of commercial (Palacos®) or EC. A histological method, based on bone architecture damage, was proposed to evaluate from 1 to 9 the histological results and the response of the infected tissue. The macrophage response was also evaluated using monoclonal antibody RAM‐11. The study showed better bone conservation with the use of EC with PLGA microspheres against the Palacos® commercial cement, including the noncontaminated and contaminated groups. © 2019 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2517–2526, 2019.

Biomimetic mineralization using matrix vesicle nanofragments.

In vitro synthesis of bone tissue has been paid attention in recent years; however, current methods to fabricate bone tissue are still ineffective due to some remaining gaps in the understanding of real in vivo bone formation process, and application of the knowledge in bone synthesis. Therefore, the objectives of this study were first, to perform a systematic and ultrastructural investigation of the initial mineral formation during intramembranous ossification of mouse calvaria from a material scientists' viewpoint, and to develop novel mineralization methods based on the in vivo findings. First, the very initial mineral deposition was found to occur at embryonic day E14.0 in mouse calvaria. Analysis of the initial bone formation process showed that it involved the following distinct steps: collagen secretion, matrix vesicle (MV) release, MV mineralization, MV rupture, and collagen fiber mineralization. Next, we performed in vitro mineralization experiments using MVs and hydrogel scaffolds. Intact MVs embedded in collagen gel did not mineralize, whereas, interestingly, MV nanofragments obtained by ultrasonication could promote rapid mineralization. These results indicate that mechanically ruptured MV membrane can be a promising material for in vitro bone tissue synthesis. © 2019 The Authors. journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1021–1030, 2019.

Development of bifunctional oriented bioactive glass/poly(lactic acid) composite scaffolds to control osteoblast alignment and proliferation.

During the bone regeneration process, the anisotropic microstructure of bone tissue (bone quality) recovers much later than bone mass (bone quantity), resulting in severe mechanical dysfunction in the bone. Hence, restoration of bone microstructure in parallel with bone mass is necessary for ideal bone tissue regeneration; for this, development of advanced bifunctional biomaterials, which control both the quality and quantity in regenerated bone, is required. We developed novel oriented bioactive glass/poly(lactic acid) composite scaffolds by introducing an effective methodology for controlling cell alignment and proliferation, which play important roles for achieving bone anisotropy and bone mass, respectively. Our strategy is to manipulate the cell alignment and proliferation by the morphological control of the scaffolds in combination with controlled ion release from bioactive glasses. We quantitatively controlled the morphology of fibermats containing bioactive glasses by electrospinning, which successfully induced cell alignment along the fibermats. Also, the substitution of CaO in Bioglass®(45S5) with MgO and SrO improved osteoblast proliferation, indicating that dissolved Mg2+ and Sr2+ ions promoted cell adhesion and proliferation. Our results indicate that the fibermats developed in this work are candidates for the scaffolds to bone tissue regeneration that enable recovery of both bone quality and bone quantity. © 2019 The Authors. journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1031–1041, 2019.

Polyelectrolyte membrane scaffold sustains growth of neuronal cells.

Cell immobilization within nano‐thin polymeric shells can provide an optimal concentration of biological material in a defined space and facilitate its directional growth. Herein, polyelectrolyte membrane scaffolds were constructed using a layer‐by‐layer approach to determine the possibility of promoting improved growth of rat cortical neuronal cells. Membrane presence was confirmed by Fourier transform infrared spectroscopy, Zeta potential, and atomic force and scanning electron microscopy. Scaffold performance toward neuronal cell growth was assessed in vitro during a 14‐day culture. Cell conditions were analyzed immunocytochemically. Furthermore, western blot and real‐time PCR analyses were used to validate the presence of neuronal and glial cells on the scaffolds. We observed that alginate/chitosan, alginate/polylysine, and polyethyleneimine/chitosan scaffolds promote neuronal growth similarly to the control, poly‐d‐lysine/laminin. We conclude that membranes maintaining cell viability, integrity and immobilization in systems supporting neuronal regeneration can be applied in neurological disease or wound healing treatment. © 2018 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 839–850, 2019.

The optimal incubation time for in vitro hemocompatibility testing: Assessment using polymer reference materials under pulsatile flow with physiological wall shear stress conditions.

During hemocompatibility testing, activation products may reach plateau values which can result in less distinction between hemocompatible and hemo‐incompatible materials. Of concern is an underestimation of the blood activation caused by the biomaterial of interest, which may result in a false assessment of hemocompatibility. To elucidate the optimal incubation time for in vitro hemocompatibility testing, we used the Haemobile circulation model with human whole blood. Blood from healthy volunteers was in vitro incubated under pulsatile flow with physiological wall shear stress conditions at 37°C for 30, 60, 120, or 240 min. Test loops containing low‐density polyethylene and polydimethylsiloxane served as low and high reference materials, that is, hemocompatible and hemo‐incompatible biomaterials, respectively. In addition, empty loops served as a negative reference. Thrombogenicity, platelet function, inflammatory response, coagulation, and hemolysis between references and incubation times were compared. We found that thrombogenicity and platelet function were significantly affected by both the duration of incubation and the type of material. In particular, thrombogenicity and platelet function assessments were affected by incubation time. We found that an exposure time of 60 min was sufficient, and for almost all variables an optimal incubation time to discriminate between the low and high reference material. © 2019 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2335–2342, 2019.

Efficacy of a synthetic calcium phosphate with submicron surface topography as autograft extender in lapine posterolateral spinal fusion.

Posterolateral spinal fusion (PLF) is a common procedure in orthopedic surgery that is performed to fuse adjacent vertebrae to reduce symptoms related to spinal conditions. In the current study, a novel synthetic calcium phosphate with submicron surface topography was evaluated as an autograft extender in a validated rabbit model of PLF. Fifty‐nine skeletally mature New Zealand white rabbits were divided into three groups and underwent single‐level intertransverse process PLF at L4‐5 using (1) autologous bone graft (ABG) alone or in a 1:1 combination with (2) calcium phosphate granules (ABG/BCPgranules), or (3) granules embedded in a fast‐resorbing polymeric carrier (ABG/BCPputty). After 6, 9, and 12 weeks, animals were sacrificed and spinal fusion was assessed by manual palpation, Radiographs, micro‐CT, mechanical testing (12 weeks only), histology, and histomorphometry. Based on all endpoints, all groups showed a gradual progression in bone formation and maturation during time, leading to solid fusion masses between the transverse processes after 12 weeks. Fusion assessments by manual palpation, radiography and histology were consistent and demonstrated equivalent fusion rates between groups, with high bilateral fusion rates after 12 weeks. Mechanical tests after 12 weeks indicated substantially lower range of motion for all groups, compared to non‐operated controls. By histology and histomorphometry, the gradual formation and maturation of bone in the fusion mass was confirmed for each graft type. With these results, we describe the equivalent performance between autograft and a novel calcium phosphate material as an autograft extender in a rabbit model of PLF using an extensive range of evaluation techniques. © 2019 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2080–2090, 2019.

PEDOT:PSS interfaces stabilised using a PEGylated crosslinker yield improved conductivity and biocompatibility.

The rapidly expanding fields of bioelectronics, and biological interfaces with electronic sensors and stimulators, are placing an increasing demand on candidate materials to serve as robust surfaces that are both biocompatible, stable and electroconductive. Amongst conductive polymers, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is a promising material in biomedical research due to its appropriate stability and high conductivity, however its intrinsic solubility requires a crosslinking process that can limit its conductivity and biocompatibility. Poly(ethylene glycol) is known to be a suitably anti-immunogenic moiety and its derivatives have been widely used for biomedical applications. In this study we investigate the application of poly(ethylene glycol)diglycidyl ether (PEGDE) as an effective crosslinker and conductive filler for PEDOT:PSS. From our interpretation of XPS analysis we hypothesise that the crosslinking reaction is occurring via the epoxy ring of PEGDE interacting with the sulfonic groups of excel PSS chains, which reaches a saturation at 3 w/v% PEGDE concentration. PEGDE crosslinked films did not disperse in aqueous environments, had enhanced electrical conductivity and imparted a significant degree of hydrophilicity to PEDOT:PSS films. This hydrophilicity and the presence of biocompatible PEGDE led to good cell viability and a significantly increased degree of cell spreading on PEDOT:PSS films. In comparison to widely reported chemical crosslinking via glycidoxy propyltrimethoxysilane (GOPS), this original crosslinking yields a highly hydrophilic 2D film substrate with increased electroconductive and biocompatibility properties, resulting in a next-generation formulation for bioengineering applications.

An in situ hydrogel based on carboxymethyl chitosan and sodium alginate dialdehyde for corneal wound healing after alkali burn.

There is currently no optimal scaffold for the transplantation of limbal stem cells (LSCs) to induce corneal reconstruction after corneal alkali burns. This study attempts to fabricate a novel in situ Alginate‐Chitosan hydrogel (ACH) for LSCs transplantation. Sodium alginate dialdehyde (SAD), a biological crosslinker, was prepared by periodate‐mediated sodium alginate oxidization. Carboxymethyl chitosan was rapidly crosslinked with SAD via Schiff's base formation between the available aldehyde and amino groups. The ACH is rapidly formed on the wound surface by self‐crosslinking without adding any chemical crosslinking component. Gelation time, transmittance, microscopic structure, equilibrium swelling, cytotoxicity, histocompatibility and degradability of the hydrogel were all examined. Rabbit primary LSCs were encapsulated in the hydrogel and transplanted to alkali burn wounds in vivo. Cornea reconstruction was evaluated by visual observation, slit lamp, histological analysis, and immunofluorescence staining. Results showed that the in situ hydrogel was highly transparent, gelated quickly, biocompatible, and had low cytotoxicity. LSCs cultured in vitro expressed the stem marker p63 but lacked the differentiated epithelial markers cytokeratin 3 and 12. Furthermore, the hydrogel encapsulating LSCs could be formed quickly on the alkali burn wound of the cornea and was shown to significantly improve epithelial reconstruction. Taken together, treatment with this novel in situ hydrogel‐mediated LSC transplantation system may serve as a rapid and effective method for corneal wound healing. © 2018 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 742–754, 2019.

Three-dimensional cultured tissue constructs that imitate human living tissue organization for analysis of tumor cell invasion.

Preventing cancer metastasis requires a thorough understanding of cancer cell invasion. These phenomena occur in human 3‐D living tissues. To this end, we developed a human cell‐based three‐dimensional (3‐D) cultured tissue constructs that imitate in vivo human tissue organization. We investigated whether our 3‐D cell culture system can be used to analyze the invasion of human oral squamous cell carcinoma (OSCC) cells. The 3‐D tissue structure consisted of five layers of normal human dermal fibroblasts along with human dermal lymphatic endothelial cell tubes and was generated by the cell accumulation technique and layer‐by‐layer assembly using fibronectin and gelatin. OSCC cells with different lymph metastatic capacity were inoculated on the 3‐D tissues and their invasion through the 3‐D tissue structure was observed. Conventional methods of analyzing cell migration and invasion, that is, 2‐D culture‐based transwell and Matrigel assays were also used for comparison. The results using the 3‐D cultured tissue constructs were comparable to those obtained using conventional assays; moreover, use of the 3‐D system enabled visualization of differential invasion capacities of cancer cells. These results indicate that our 3‐D cultured tissue constructs can be a useful tool for analysis of cancer cell invasion in a setting that reflects the in vivo tissue organization. © 2018 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 292–300, 2019.