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- ArticleJones T, Zhang B, Major S, Webb A.J Biomed Mater Res B Appl Biomater. 2020 04;108(3):619-628.Current treatments for glioblastoma have failed to significantly increase patient survival, are extremely cytotoxic, can cause severe side effects, and are ineffective. Given these limitations, drugs other than cytotoxic chemotherapeutic agents are being explored. Recent studies show that all-trans retinoic acid (ATRA) could be effective on cancer cells as they have been shown to suppress carcinogenesis in a variety of tumor types and can reverse premalignant lesions and inhibit the development of secondary tumors in the head and neck of cancer patients. However, the therapeutic effects of retinoids such as ATRA are undermined by its rapid in vivo metabolism by cytochrome P450 enzymes, difficulty in crossing the blood-brain barrier, and sensitivity to isomerization/degradation. To overcome these limitations, we have developed a porous poly(1,8-octanediol-co-citrate; POC) wafer that stabilizes all-trans retinoic acid, while slowly releasing ATRA over 3 months. Release of ATRA from POC wafers inhibited proliferation of U87MG (glioblastoma) cells and caused upregulation in genes associated with differentiation into normal phenotype and apoptosis. Therefore, ATRA eluting poly(diol citrate) wafers are a promising treatment option compared to traditional cytotoxic chemotherapeutic agents.
- ArticleLee EMR, Borges R, Marchi J, de Paula Eduardo C, Marques MM.J Biomed Mater Res B Appl Biomater. 2020 04;108(3):939-947.This in vitro study aimed to analyze the physical and chemical characteristics of the hypersensitive human dentin-like surface after application of a bioactive glass (BG) paste (BG/Ac) irradiated or not with high-power lasers. Dentin specimens were treated with 17% Ethylenediamine tetraacetic acid (EDTA) solution to mimic a hypersensitive dentin and then submitted to neodymium: yttrium-aluminum-garnet (Nd:YAG) laser or CO2 laser irradiation prior and after application of BG/Ac. Characterizations were performed by using X-ray diffraction, Fourier transformed infrared spectroscopy, scanning electron microscopy, and energy dispersive X-ray spectroscopy. The results suggested that application of BG/Ac by itself caused some obstructions of dentinal tubules. Nd:YAG laser irradiation reduced the opening of the dentinal tubules with no changes in the collagen structure. CO2 laser irradiation caused dentin melting and resolidification along with cracks and chemical changes in collagen fibers. However, when BG/Ac paste was irradiated with lasers, a sequence of surface reactions between glass and dentin interface led to the formation of an amorphous hydroxyapatite layer, similar to that of an inorganic component of the normal dentin. Moreover, BG/Ac was able to prevent the formation of cracks and degradation of collagen fibers caused by CO2 irradiation. Overall, this study supports that application of BG/Ac paste irradiated by high-power laser could represent an effective and long-lasting therapeutic approach for dentin hypersensitivity.
- ArticleVenugopal B, Shenoy SJ, Mohan S, Anil Kumar PR, Kumary TV.J Biomed Mater Res B Appl Biomater. 2020 04;108(3):1033-1045.Limbal stem cell deficiency (LSCD) is the loss of limbal stem cells that reside in the corneoscleral junction resulting in vision loss or blindness. Bilateral LSCD is usually treated by allogeneic corneal transplantation, with instances of tissue rejection or failure in long-term follow-up. This study aims to use adipose mesenchymal stem cells (ASC) as an alternative autologous cell source for treating bilateral limbal deficiency conditions. ASCs derived from rabbit fat tissue were differentiated into corneal epithelial lineage using limbal explant condition media. Apart from transdifferentiation, ASC sheets were developed to facilitate effective delivery of these cells to the damage site. A thermoresponsive polymer N-isopropylacrylamide-co-glycidylmethacrylate (NGMA) was synthesized and characterized to demonstrate ASC sheet formation. Transdifferentiated ASCs showed positive expression of corneal epithelial marker CK3/12 on immunostaining, supported by gene expression studies. in vivo studies by transplanting cell sheet in rabbit models of corneal injury showed clear and smooth cornea in comparison to the sham models. Histology revealed a sheet of cells aligned and integrated on to the injured corneal surface, 1 month posttransplantation. Identifying ASCs as an alternative cell source along with cell sheet technology will be a novel step in the field of corneal surface therapies.
- ArticleBudnicka M, Szymaniak M, Kołbuk D, Ruśkowski P, Gadomska-Gajadhur A.J Biomed Mater Res B Appl Biomater. 2020 04;108(3):868-879.Implants in the form of polymer scaffolds are commonly used to regenerate bone tissue after traumas or tooth extractions. However, few implant formation methods enable building polymer scaffolds allowing to reconstruct larger bone losses without immune response. Spacious, porous poly-l-lactide implants with considerable volume were obtained using the phase inversion method with the freeze-extraction variant. The calcium phosphate (CaP) coating was deposited on implant surfaces with the biomimetic method to improve the implant's osteoconductivity. The substitues morphology was characterized-porosity, size and shape of pores; mechanical properties, mass absorbability of implants before and after mineralization. The characteristics were provided with scanning electron microscopy (SEM), static compression test and hydrostatic weighing, respectively. The presence of CaPs in the entire volume of the implant was confirmed with SEM and infrared spectroscopy with Fourier transform (FTIR). The biocompatibility of scaffolds was confirmed with in vitro quantitative test and microscopic observations. The obtained results show that the implants can be used in tissue engineering as a vehicle of platelet-rich plasma to regenerate critical spongy bone losses.
- ArticleSheftel Y, Ruddiman F, Schmidlin P, Duncan W.J Biomed Mater Res B Appl Biomater. 2020 04;108(3):750-759.Autogenous bone grafting requires a donor site and may lose substantial volume during remodeling. Several bone replacement materials (BRMs) are under development to overcome these limitations, especially for indications for minimally intervention surgeries. The objective of our study was to assess the potential of an equine collagen cone reinforced with biphasic calcium phosphate (CC-BCP) particles and deproteinized bovine bone matrix (BBM) coated with polylactic acid, and poly-ε-caprolactone copolymer (BBM-PCC) and then to compare the outcomes with a deproteinized BBM and an equine CC without a filler in a sheep sinus grafting model in the Elleven female sheep were selected. Two experimental sites on each side of the animals were prepared using an extraoral approach for maxillary sinus wall. The four treatments were performed in each animal through a standardized 10-mm access window. While the BBM access was covered with a collagen membrane, all other sites were closed with an equine collagen membrane. All animals were euthanized after 16 weeks. New bone (NB), residual graft particles, and connective tissue were measured in undemineralized resin-embedded sections. As a result, one sheep did not survive the surgery. All sites in the remaining 10 sheep healed uneventfully. All CC and BBM-PCC grafts resorbed and failed to augment the sinuses. BBM and CC-BCP, in contrast, showed some histologic evidence of NB and surgical site augmentation. The NB fraction in the latter two groups accounted for 10 ± 9 and 4 ± 5%, respectively (p > 0.05). In conclusion, BBM-PCC and collagen cone performed poorly for sinus floor augmentation, while deproteinised BBM and reinforced collagen cone demonstrated comparable outcomes.
- ArticlePopescu RA, Tăbăran FA, Bogdan S, Fărcăṣanu A, Purdoiu R, Magyari K, Vulpoi A, Dreancă A, Sevastre B, Simon S, Papuc I, Baia L.J Biomed Mater Res B Appl Biomater. 2020 04;108(3):1129-1140.In the present study, scaffolds based on alginate-pullulan-bioactive glass-ceramic with 0.5 and 1.5 mol % copper oxide were orthotopically implanted in experimental rat models to assess their ability to heal an induced bone defect. By implying magnetic resonance and imaging scans together with histological evaluation of the processed samples, a progressive healing of bone was observed within 5 weeks. Furthermore, as the regenerative process continued, new bone tissue was formed, enhancing the growth of irregular bone spicules around the scaffolds. A significantly higher amount of new bone was formed (37%) in the defect that received the composite with 1.5 mol % CuO (in glass-ceramic matrix) content implant. Nevertheless, the bone regeneration obtained by scaffold with 0.5 mol % CuO implanted is comparable with the alginate-pullulan-β-tricalcium phosphate/hydroxiapatite composite implant. The assessed amount of new bone formed was found to be between 29.75 and 37.15% for all the composition involved in the present study. During this process a regeneration process was shown when the alginate-pullulan composite materials were involved, fact that indicate the great potential of these materials to be used in tissue engineering.
- ArticleCoathup M, Campion C, Blunn G.J Biomed Mater Res B Appl Biomater. 2020 04;108(3):612-618.A limitation in the use of calcium phosphate (CaP) is that in its raw form, it comprises blocks or granules, which are limited in their utility for orthopedic surgery and a number of commercial bone grafts are supplied within an aqueous based carboxymethyl cellulose (CMC) putty. Our hypothesis was that CMC combined with a porous silicate-substituted CaP (SiCaP) scaffold would have no negative effect on bone formation after implantation in an ovine femoral condyle. Defects were either (a) empty or filled with (b) SiCaP granules, (c) CMC-SiCaP Putty or (d) a SiCaP press-fit dry block. Scaffolds were identical in composition and remained in vivo for 4, 8, and 12 weeks. Bone apposition rates, bone area, percentage of bone-implant contact and graft area were quantified. At 4 and 8 weeks, significantly more new bone and percentage of bone-implant contact was measured within granules when compared with both putty and block scaffolds. At 12 weeks, significantly increased bone was measured for the granules when compared with blocks and no significant difference was found when the granules and putty scaffolds were compared. Results showed the disadvantageous effect that CMC may have on early bone growth and that granules increased new bone formation when compared with a press-fit block composed of the same material.
- ArticleDavoodzadeh N, Cano-Velázquez MS, Halaney DL, Sabzeghabae A, Uahengo G, Garay JE, Aguilar G.J Biomed Mater Res B Appl Biomater. 2020 04;108(3):709-716.The "Window to the Brain" is a transparent cranial implant under development, based on nanocrystalline yttria-stabilized zirconia (nc-YSZ) transparent ceramic material. Previous work has demonstrated the feasibility of this material to facilitate brain imaging over time, but the long-term stability of the material over decades in the body is unknown. In this study, the low-temperature degradation (LTD) of nc-YSZ of 3, 6, and 8 mol % yttria is compared before and after accelerated ageing treatments following ISO standards for assessing the ageing resistance of zirconia ceramics. After 100 hr of accelerated ageing (equivalent to many decades of ageing in the body), the samples do not show any signs of phase transformation to monoclinic by X-ray diffraction and micro-Raman spectroscopy. Moreover, the mechanical hardness of the samples did not decrease, and changes in optical transmittance from 500 to 1000 nm due to ageing treatments was minimal (below 3% for all samples), and unlikely to be due to phase transformation of surface crystals to monoclinic. These results indicate the nc-YSZ has excellent ageing resistance and can withstand long-term implantation conditions without exhibiting LTD.
- ArticleMony MP, Anilkumar TV.J Biomed Mater Res B Appl Biomater. 2020 04;108(3):1057-1067.Treatment with cross-linking agents for stabilizing biomolecules is an integral step during the preparation of many extracellular matrix-based tissue engineering scaffolds from mammalian organs. However, excess cross-linking may cause nonavailability of biomolecules and consequent deterioration of bioinductive properties of the scaffold. The present study considered controlling the extent of cross-linking in a porcine cholecyst extracellular matrix scaffold prepared by a nonenzymatic and nondetergent method, by ex situ incubation of the source organ in varying concentrations of neutral buffered formaldehyde (10, 4, 1 or 0%; v/v) for in situ cross-linking of biomolecules. Reduction of the formaldehyde concentration resulted in an increase in the extent of biodegradation and a decrease in the compactness of the mesh-like surface microarchitecture of the scaffold. Retention of collagen was maximum when treated with 10% neutral buffered formaldehyde without any variation in the content of elastin and sulphated glycosaminoglycans. Although there was a reduction in the quantity of growth factors following the cross-linking, fibroblasts remained viable on the scaffolds. The retention of major biomolecule was maximum and autodigestion was minimum in the scaffold prepared by the ex situ treatment of cholecyst in 10% neutral buffered formalin and found suitable for preparing the tissue engineering scaffold.
- ArticleZhang X, Dai J, Dong Q, Ba Z, Wu Y.J Biomed Mater Res B Appl Biomater. 2020 04;108(3):698-708.The microstructures, corrosion behavior, and mechanical degradation of the as-extruded Mg-6.0Gd-0.5Zn-0.4Zr (wt %, GZ60K) and Mg-6.0Gd-1.0Zn-0.4Zr (wt %, GZ61K) alloys were investigated. In both alloys, stacking faults and precipitates are formed in the recrystallized microstructures. The corrosion rate of GZ61K calculated by the hydrogen evolution in simulated body fluid is 0.34 ± 0.13 mm/year, which is lower than that of GZ60K (0.45 ± 0.09 mm/year); and the current density of GZ61K (5.23 ± 1.41 μA cm-2 ) is much lower than that of GZ60K (11.95 ± 3.37 μA cm-2 ). The corrosion results indicate GZ61K is more resistant to corrosion than GZ60K, but GZ60K presents more uniform corrosion mode as compared to GZ61K. After immersion in simulated body fluid for 7, 14, and 21 days, a slight decrease in the strength of both alloys is observed. The yield strength half-life is assessed for mechanical degradation and determined to be 125 and 85 days for GZ60K and GZ61K, respectively. The as-extruded GZ60K alloy with more uniform corrosion and longer mechanical integrity shows promising potential for orthopedic application.
- ArticleSuhrland C, Truman JP, Obeid LM, Sitharaman B.J Biomed Mater Res B Appl Biomater. 2020 04;108(3):1141-1156.The bioactive sphingolipid ceramide has many important roles in cell signaling processes, particularly in signaling programmed cell death in cancer. However, ceramide levels are often impaired in multi-drug resistant and radiation resistant cancers due to the dysregulation of ceramide metabolism. Restoration of ceramide levels through external delivery therefore represents a potential therapeutic target for the treatment of resistant cancers. However, as a lipid, ceramide is extremely hydrophobic and requires a delivery system to enter cells. Here we report the development of a method to load significant amounts of the long chain C16 and C24 ceramides onto oxidized graphene nanoribbons (O-GNRs) derived from carbon nanotubes. Using O-GNRs as a delivery system for these ceramides, we were able to induce significant biological effects in HeLa cells in conjunction with C6 ceramide and ultraviolet radiation treatment. However, we found that O-GNRs themselves exert significant biological effects and can interfere with the actions of these ceramides and ultraviolet treatment. Loading of ceramides onto O-GNRs did not have a significant effect on the entry of the nanoparticles into cells. Despite the need for further improvement, these data represent an important first step in the development of O-GNRs as a delivery system for long chain ceramides.
- ArticleVanhatupa S, Miettinen S, Pena P, Baudín C.J Biomed Mater Res B Appl Biomater. 2020 04;108(3):819-833.Ti scaffolds combined with autologous human adipose-derived mesenchymal stem cells (hASCs) have been successfully applied for regenerative cranio-maxillofacial bone therapies. Future challenges reside in regeneration of larger bone defects and displacement of the permanent Ti structure, thus, advanced resorbable scaffolds are needed. Composites of β-Ca3 (PO4 )2 with 80 and 60 wt % of CaMg(SiO3 )2 with improved mechanical properties compared to tricalcium phosphate (TCP) materials are presented. Synthetic CaMg(SiO3 )2 and a precursor of Ca3 (PO4 )2 were used to fabricate the composites and a reference β-Ca3 (PO4 )2 material by uniaxial pressing and solid state sintering. Optimum sintering temperature of 1225°C was selected. Microstructural analysis and Weibull distributions of tensile strengths determined by the diametral compression of discs test are reported. Thermodynamic simulation of the dissolution process in simulated body fluid body fluid was done. The biological response with hASCs was analyzed using basic and osteogenic media. Viability and osteogenic potential-LIVE/DEAD assay; alkaline phosphatase activity and collagen type-I production-were characterized. The composites have higher tensile strength (>3×) than TCP materials, for similar reliability, and support viability and osteogenic differentiation of hASCs. Resorption of the high strength phase diopside is the slowest. The promising results reported here suggest possible uses of these bioactive β-Ca3 (PO4 )2 -CaMg(SiO3 )2 ceramics together with hASCs in bone tissue engineering.
- ArticleAlshamrani AA, De Souza GM.J Biomed Mater Res B Appl Biomater. 2020 04;108(3):1068-1076.This study aimed to evaluate the effect of radiation therapy (RT) on mechanical properties and translucency of monolithic zirconia. Yttria- stabilized zirconia (Y-PSZ) materials (14 × 4.0 × 1.5 mm) were divided in four experimental groups (n = 30): High-translucency/control (HT/C), high-translucency/irradiated (HT/I), low-translucency/control (LT/C), low-translucency/irradiated (LT/I). Irradiated specimens were submitted to a single dose irradiation of 70 Gray. Flexural strength (n = 10) (FS-3-point bending test), fatigue limits (n = 15) at 100,000 cycles (FLs-staircase approach), and translucency (n = 5) (TP-dental spectrometer) were analyzed. X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to characterize the materials. FS and TP data were analyzed by one-way Analysis of Variance (ANOVA) and Tukey HSD. FLs were analyzed using Dixon and Mood method, and Kaplan-Meier survival analysis. RT affected FS of LT zirconia (p = .032) but not of HT zirconia (p = .86). FLs and TP of both materials were not affected by RT (p > .05). Higher cubic content after RT was observed. In conclusion, RT may affect flexural strength and crystalline content of zirconia-based materials, but this effect was not observed under fatigue. Translucency of Y-PSZ restorations is also not affected by RT.
- ArticleIslam MT, Sharmin N, Rance GA, Titman JJ, Parsons AJ, Hossain KMZ, Ahmed I.J Biomed Mater Res B Appl Biomater. 2020 04;108(3):674-686.Varying formulations in the glass system of 40P2 O5 ─(24 - x)MgO─(16 + x)CaO─(20 - y)Na2 O─yTiO2 (where 0 ≤ x ≤ 22 and y = 0 or 1) were prepared via melt-quenching. The structure of the glasses was confirmed by X-ray diffraction (XRD), Fourier transform infrared (FTIR), micro Raman and solid-state nuclear magnetic resonance (NMR) spectroscopies. The thermal properties and the activation energy of crystallization (Ec ) were measured using thermal analysis and the Kissinger equation, respectively. The glass forming ability of the formulations investigated was seen to decrease with reducing MgO content down to 8 mol% and the glass stability region also decreased from 106 to 90°C with decreasing MgO content. The activation energy of crystallization (Ec ) values also decreased from 248 (for 24 mol% MgO glass) to 229 kJ/mol (for the 8 mol% MgO content) with the replacement of MgO by CaO for glasses with no TiO2 . The formulations containing less than 8 mol% MgO without TiO2 showed a strong tendency toward crystallization. However, the addition of 1 mol% TiO2 in place of Na2 O for these glasses with less than 8 mol% MgO content, inhibited their crystallization tendency. Glasses containing 8 mol% MgO with 1 mol% TiO2 revealed a 12°C higher glass transition temperature, a 14°C increase in glass stability against crystallization and a 38 kJ/mol increase in Ec in comparison to their non TiO2 containing counterpart. NMR spectroscopy revealed that all of the formulations contained almost equal percentages of Q1 and Q2 species. However, FTIR and Raman spectroscopies showed that the local structure of the glasses had been altered with addition of 1 mol% TiO2 , which acted as a network modifier, impeding crystallization by increasing the cross-linking between phosphate chains and consequently leading to increased Ec as well as their glass forming ability.
- ArticleBretschneider H, Mettelsiefen J, Rentsch C, Gelinsky M, Link HD, Günther KP, Lode A, Hofbauer C.J Biomed Mater Res B Appl Biomater. 2020 04;108(3):1117-1128.For cementless total joint replacement implants, the biological response to physicochemical surface characteristics is crucial for their success that depends on fixation by newly formed bone. In this study, the surface of TiAl6V4 (Tilastan®) implants was modified by (a) corundum blasting, (b) corundum blasting followed by electrochemical calcium phosphate (CaP) deposition, and (c) titanium plasma spraying followed by electrochemical CaP deposition. All modifications resulted in a surface roughness suitable to enhance primary implant stabilization and to favor osteoblast adhesion and function; the thin, biomimetic CaP coating is characterized by fast resorbability and served as chemical cue to stimulate osteogenesis. After implantation in a full weight-bearing rabbit intramedullary distal femur model, osseointegration was investigated after 3, 6, and 12 weeks. For all modifications, new bone formation, occurring from the endosteum of the femoral cortical bone, was observed in direct contact to the implant surface after 3 weeks. At the later time points, maturation of the woven bone into lamellar bone with clearly defined osteons was visible; the remodeling process was accelerated by the CaP coating. The ingrowth of newly formed bone into the pores of the titanium plasma sprayed surfaces indicates a strong interlock and finally implant fixation. Our findings indicate a positive impact of the tested surface modifications on osseointegration.
- ArticleLee HS, Jeong MS, Ko SC, Heo SY, Kang HW, Kim SW, Hwang CW, Lee KD, Oak C, Jung MJ, Oh J, Park WS, Choi IW, Jung WK.J Biomed Mater Res B Appl Biomater. 2020 04;108(3):1046-1056.Prolonged endotracheal intubation is the most common cause of tracheal stenosis, which may lead to serious airway obstruction. Development of an endotracheal tube coated with biomaterials that exhibit anti-inflammatory or anti-fibrogenic effects may prevent tracheal stenosis. This study demonstrates that an endotracheal tube coated with phlorotannin, which is present in extracts of the brown alga Ecklonia cava, can prevent tracheal stenosis in a rabbit model. An in vitro study shows that phlorotannin inhibits proliferation of human tracheal fibroblasts treated with transforming growth factor β1. Phlorotannin-coated endotracheal tubes show steady release of phlorotannin for up to 7 days, and removal of the tube 1 week after insertion reveals a reduction in both fibrogenesis and thickening of tracheal submucosa. Western blot analysis of tracheal tissues after removal of the phlorotannin-coated tube shows decreased protein expression levels of phenotypic markers of fibrosis such as collagen type I and α-smooth muscle actin. The ability of phlorotannin-coated endotracheal tube to prevent tracheal stenosis caused by endotracheal intubation indicates that phlorotannin may be considered as a candidate biomaterial for coating the cuff of endotracheal tubes to prevent tracheal stenosis.
- ArticleSasaki JI, Yoshimoto I, Katata C, Tsuboi R, Imazato S.J Biomed Mater Res B Appl Biomater. 2020 04;108(3):958-964.Freeze-dry processing improves the operability and stability of cell-based biomaterials and facilitates sterilization for clinical application. However, there is no established freeze-drying protocol for engineered tissues. Recently, we reported that biomimetic bone tissues can be fabricated using scaffold-free three-dimensional (3D) cell constructs with potential applications as bone graft materials. The purpose of this study was to assess the influence of freeze drying on the morphology and components of 3D cell constructs. Cell constructs freeze dried in phosphate buffered saline (PBS) maintained organic and inorganic components; whereas sodium citrate buffer (SCB)-treated constructs had significantly lower amounts of calcium and bone-related proteins. Alkaline phosphatase (ALP) activity in cell constructs was maintained by freeze drying in 10% sucrose-containing PBS, whereas cell constructs treated with PBS without sucrose or with sucrose-containing SCB showed significant reductions of ALP activity. In this study, we found that sucrose-containing phosphate buffer was suitable for freeze drying to maintain minerals and protein functions within 3D cell constructs, whereas citrate buffer was inappropriate. The insights gained by this study may facilitate the development of novel cell-based biomaterials fabricated by tissue engineering approaches and bone graft biomaterials.
- ArticleSuo H, Li L, Zhang C, Yin J, Xu K, Liu J, Fu J.J Biomed Mater Res B Appl Biomater. 2020 04;108(3):990-999.Glucosamine (GlcN) has been widely used to reduce joint pain and osteoarthritis progression, but the efficacy of GlcN remains controversial because of the low GlcN concentration reaching the articular cavity. The aim of this study is to provide an effective approach of GlcN delivery to a target site using photocrosslinkable methacrylated gelatin (GelMA)-based hydrogels, where GlcN could be gradually released during the degradation of the GelMA hydrogel. Herein, GlcN was acrylated as the acryloyl glucosamine (AGA) and covalently grafted to GelMA, and more than 87.7% of 15% (w/v) GelMA hydrogel was grafted with AGA. Moreover, in vitro outgrowth and apoptosis assay of bone marrow stem cells (BMSCs) demonstrated that the GelMA-AGA hydrogels had better biocompatibility, larger cell attachment, and higher cell viability than pure GlcN and AGA materials. Also, 15% (w/v) GelMA-AGA hydrogel was injected into the defect site for in vivo rabbit cartilage repair. Compared with oral administration of pure GlcN and injection of pure GelMA, the repaired cartilages using GelMA-AGA hydrogels had the smoothest surface of the defect site, filling more than 95% defect bulk. The similar content of glycosaminoglycans to the native tissue and the maximum amount of type II collagen was found in the repaired cartilage using GelMA-AGA hydrogels, indicating the outgrowth of hyaline cartilage.
- ArticleHong H, Park SM, Kim D, Park SJ, Kim DS.J Biomed Mater Res B Appl Biomater. 2020 04;108(3):1000-1009.Despite the potential of a collagen construct with a stiffness gradient for investigating cell-extracellular matrix (ECM) stiffness interaction or recapitulating an in vivo tissue interface, it has been developed in a limited way due to the low and poorly controllable mechanical properties of the collagen. This study proposes a novel fabrication process to achieve a compressed collagen construct with a stiffness gradient, named COSDIENT, at a level of ~ 1 MPa while maintaining in vivo ECM-like dense collagen fibrillar structures. The COSDIENT was fabricated by collagen compression followed by grayscale mask-assisted UV-riboflavin crosslinking. The collagen compression process enabled the remarkable increase in the stiffness of the collagen gel from ~ 1-10 kPa to ~ 1 MPa by physical compaction. The subsequent UV-riboflavin crosslinking with a continuous-tone grayscale mask could simply generate a gradual change of UV irradiation followed by modulating riboflavin-mediated crosslinking, thereby resulting in a continuous stiffness gradient with a range of 1.16-4.38 MPa in the single compressed collagen construct. The suggested grayscale mask-assisted photochemical crosslinking had no effect on the physical and optical properties of the original compressed collagen construct, while inducing gradual changes of chemical bonds among collagen fibrils. A skin wound healing assay with epidermal keratinocytes was finally applied as an application example of the COSDIENT to examine the effect of stiffness on the skin keratinocyte behavior.
- ArticleMaeng J, Chakraborty B, Geramifard N, Kang T, Rihani RT, Joshi-Imre A, Cogan SF.J Biomed Mater Res B Appl Biomater. 2020 04;108(3):880-891.The deposition and properties of sputtered iridium oxide films (SIROFs) using water vapor as a reactive gas constituent are investigated for their potential as high-charge-capacity neural stimulation electrodes. Systematic investigation through a series of optical and electrochemical measurements reveals that the incorporation of water vapor as a reactive gas constituent, along with oxygen, alters the reduction-oxidation (redox) state of the plasma as well as its morphology and the electrochemical characteristics, including the cathodal charge-storage capacity (CSCc ) and charge-injection capacity (CIC), of the SIROF. An apparent optimal O2 :H2 O gas ratio of 1:3 produced SIROF with a CSCc of 182.0 mC cm-2 μm-1 (median, Q1 = 172.5, Q3 = 193.4, n = 15) and a CIC of 3.57 mC cm-2 (median, Q1 = 2.97, Q3 = 4.58, n = 12) for 300-nm-thick films. These values are higher than those obtained with SIROFs deposited using no water vapor by a factor of 2.3 and 1.7 for the CSCc and CIC, respectively. Additionally, the SIROF showed minimal changes in electrochemical characteristics over 109 pulses of constant current stimulation and showed no indication of cytotoxicity toward primary cortical neurons in a cell viability assay. These results warrant investigation of the chronic recording and stimulation capabilities of the SIROF for implantable microelectrode arrays.