Journal of Biomedical Materials Research Part B Applied Biomaterials

Published by Wiley and Society for Biomaterials
Online ISSN: 1552-4981
Print ISSN: 1552-4973
Discipline: Polymer Science
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Aims and scope

Journal of Biomedical Materials Research – Part B: Applied Biomaterials is a highly interdisciplinary peer-reviewed journal serving the needs of biomaterials professionals who design, develop, produce and apply biomaterials and medical devices. It has the common focus of biomaterials applied to the human body and covers all disciplines where medical devices are used.

Papers are published on biomaterials related to medical device development and manufacture, degradation in the body, nano- and biomimetic- biomaterials interactions, mechanics of biomaterials, implant retrieval and analysis, tissue-biomaterial surface interactions, wound healing, infection, drug delivery, standards and regulation of devices, animal and pre-clinical studies of biomaterials and medical devices, and tissue-biopolymer-material combination products.

Recent publications
Antibacterial activity of single‐ and dual‐drug loaded UHMWPE against (A) MSSA, and (B) biofilm‐forming S. epidermidis measured using the “daughter” cell method.” Dashed lines represent “daughter” cell count measured in the presence of virgin UHMWPE. Data points are shown as the mean value ± standard deviation
Cumulative fractional release of (A) bupivacaine and (B) tolfenamic acid from single‐ and dual‐drug loaded UHMWPE measured in‐vitro in PBS at 37°C. Figure also shows combinatory elution plots for (C) bupivacaine and (D) tolfenamic acid. Dashed lines represent the case of no combinatorial effect on drug elution from dual‐drug loaded UHMWPE; areas above the dashed lines represent cases of synergistic elution; areas below the dashed lines represent cases of antagonistic elution. Data points are shown as the mean value ± standard deviation
EDX images collected from single‐ and dual‐drug loaded UHMWPE (Black indicates the polymer). The raw data were analyzed using the adaptive thresholding method. (A) 10%BP‐PE, (B) 7%BP/3%TA‐PE, (C) 6%BP/4%TA‐PE, (D) 5%BP/5%TA‐PE, (E) 4%BP/6%TA‐PE, and (F) 10%TA‐PE
Tensile mechanical properties of single‐ and dual‐drug loaded UHMWPE: (A) UTS and (B) EAB. Data points are shown as the mean value ± standard deviation
Osteoblast viability in the presence of single‐ and dual‐drug loaded UHMWPE, as well as virgin UHMWPE as measured using the XTT assay. Data points are shown as the mean value ± standard deviation
  • Dmitry GilDmitry Gil
  • Shannon HugardShannon Hugard
  • Nikolay BorodinovNikolay Borodinov
  • [...]
  • Ebru OralEbru Oral
Total joint arthroplasty is one of the most common surgeries in the United States, with almost a million procedures performed annually. Periprosthetic joint infections (PJI) remain the most devastating complications associated with total joint replacement. Effective antibacterial prophylaxis after primary arthroplasty could substantially reduce incidence rate of PJI. In the present study we propose to provide post‐arthroplasty prophylaxis via dual‐analgesic loaded ultra‐high molecular weight polyethylene (UHMWPE). Our approach is based on previous studies that showed pronounced antibacterial activity of analgesic‐ and NSAID‐loaded UHMWPE against Staphylococci. Here, we prepared bupivacaine/tolfenamic acid‐loaded UHMWPE and assessed its antibacterial activity against Staphylococcus aureus and Staphylococcus epidermidis. Dual‐drug loaded UHMWPE yielded an additional 1–2 log reduction of bacteria, when compared with single‐drug loaded UHMWPE. Analysis of the drug elution kinetics suggested that the observed increase in antibacterial activity is due to the increased tolfenamic acid elution from dual‐drug loaded UHMWPE. We showed that the increased fractal dimension of the drug domains in UHMWPE could be associated with increased drug elution, leading to higher antibacterial activity. Dual‐analgesic loaded UHMWPE proposed here can be used as part of multi‐modal antibacterial prophylaxis and promises substantial reduction in post‐arthroplasty mortality and morbidity.
(A) Dynamic light scattering (DLS), (B) UV–vis spectra and a picture (inset) of freshly prepared AuNPs; (C) pictures of pristine and BOA‐coated brackets
Scanning electron microscope (SEM) (A, E), atomic force microscopy (AFM) (B, F), energy‐dispersive spectrometer (EDS) (C, G), and X‐ray photoelectron spectroscopy (XPS) (D, H) characterization of pristine versus BOA‐covered brackets (respectively). AuNPs are visible, but the roughness of the surfaces does not differ significantly (10.4 nm and 13.1 nm for raw and BOA‐covered brackets, respectively). Scale bars correspond to 500 nm.
SEM pictures of BOA‐coated brackets before and after 50 cycles of brushing (100 min in total). Scale bars correspond to 500 nm.
Microscopic pictures of L929 cells exposed to (A) 100% polyethylene extract (negative control), (B) 0.1% solution of Triton X‐100 (positive control), (C) 100% extract from BOA covered brackets. Scale bars correspond to 200 μm.
  • Jan ŁyczekJan Łyczek
  • Bartłomiej BończakBartłomiej Bończak
  • Izabela KrzymińskaIzabela Krzymińska
  • [...]
  • Jan PaczesnyJan Paczesny
The study's main objective is to limit bacterial biofilm formation on fixed orthodontic appliances. Bacterial biofilm formation on such devices (e.g., brackets) causes enamel demineralization, referred to as white spot lesions (WSL). WSL is significant health, social and economic problem. We provide a nanotechnology‐based solution utilizing a nanocomposite of gold nanoparticles embedded in a polyoxoborate matrix (BOA: B—boron, O—oxygen, A—gold, Latin aurum). The nanocomposite is fully inorganic, and the coating protocol is straightforward, effective, and ecologically friendly (low waste and water‐based). Prepared coatings are mechanically stable against brushing with a toothbrush (up to 100 min of brushing). Bacteria adhesion and antibacterial properties are tested against Streptococcus mutans—common bacteria in the oral cavity. BOA reduces the adhesion of bacteria by around 78%, that is, from around 7.99 × 10⁵ ± 1.33 × 10⁵ CFU per bracket to 1.69 × 10⁵ ± 3.07 × 10⁴ CFU per bracket of S. mutans detached from unmodified and modified brackets, respectively. Modified fixed orthodontic brackets remain safe for eukaryotic cells and meet ISO 10993‐5:2009 requirements for medical devices. The gathered data show that BOA deposited on orthodontic appliances provides a viable preventive measure against bacteria colonization, which presents frequent and significant complications of orthodontic treatment.
  • Xu LiuXu Liu
  • Chenshu WangChenshu Wang
  • Mingyu DuMingyu Du
  • [...]
  • Jiang YuanJiang Yuan
Nitric oxide (NO) releasing vascular graft is promising due to its merits of thromboembolism reduction and endothelialization promotion. In this study, keratin‐based NO donor of S‐nitrosated keratin (KSNO) was blended with poly(vinyl alcohol) (PVA) and further crosslinked with sodium trimetaphosphate (STMP) to afford PVA/KSNO biocomposite films. These films could release NO sustainably for up to 10 days, resulting in the promotion of HUVECs growth and the inhibition of HUASMCs growth. In addition, these films displayed good blood compatibility and antibacterial activity. Taken together, these films have potential applications in vascular grafts.
This work aimed the development and evaluation of the wound healing activity of films based on sodium alginate, polyvinyl alcohol (PVA) and Ca²⁺ loaded with Agaricus blazei Murill hydroalcoholic extract (AbE). Firstly, AbE was prepared using a previously standardized methodology. The films were prepared by casting technique and cross‐linked with Ca²⁺ using CaCl2 as cross‐linking agent. The physicochemical, morphological and water vapor barrier properties of the films were analyzed and the pre‐clinical efficacy was investigated against the cutaneous wound model in mice. The films showed barrier properties to water vapor promising for wound healing. AbE showed physical and chemical interactions between both polymers, noticed by Fourier transform infrared spectroscopy, X‐ray diffraction, scanning electron microscopy, and thermal analysis. The delivery of AbE in alginate/PVA films enhanced the antioxidant and wound healing properties of these polymers. Consequently, a reduction of malondialdehyde levels was observed, as well as an increase of the epidermis/dermis thickness and enhancement in collagen I deposition. Thus, these formulations are promising biomaterials for wound care and tissue repairing.
Sr²⁺ release and XRD analysis of different coatings after PBS immersion. Cumulative (A) and average daily (B) Sr²⁺ release from different coatings after PBS immersion for 1, 3, 7, 30, and 120 days. Sr²⁺ shows a burst release within the first 3 days, a fast release from day 4 to day 7, a relatively slow release from day 8 to day 30, and a steady release thereafter. (C) XRD phase patterns of different coatings after 120 days' PBS immersion. Diffraction peak of SrTiO3 can be observed in group Sr90 and Sr120, whereas it disappears in group Sr30 and Sr60. In contrast, diffraction peaks of pure titanium and rutile and anatase TiO2 exist in all five groups and the peak patterns are similar
Surface micromorphology of Sr/Ag‐containing TiO2 coatings with different Sr contents. (A) The samples prepared by MAO. The color of the samples becomes more lightened with the increase of Sr concentration in electrolyte solutions. (B) Micromorphology of different coatings under SEM with different magnifications. Micropores with a diameter of 0.5 to 5 μm are well separated and homogeneously distributed in five groups of coatings. (C) Pore size distribution and average pore size on different coatings
Physicochemical characteristic analysis of Sr/Ag‐containing TiO2 coatings. (A) Element distribution of Ti, O, Sr, and Ag on TiO2 coatings in group Sr90. (B) Phase compositions in different coatings analyzed by XRD. (C) Surface roughness (Ra) of samples in five groups. (D) Hydrophilicity of samples in five groups detected by water contact‐angle measurement
Cell adhesion, proliferation and alkaline phosphatase (ALP) activity analysis of MC3T3‐E1 cells on different coatings without and after PBS immersion (n = 3). (A) Fluorescent observation of cell adhesion. Cell nuclei are labeled with propidium iodide (PI). (B) Quantity analysis of adhering cells on five coatings. (C) Cell proliferation detected by CCK‐8 analysis. (D) ALP activity analysis of cells on five coatings.* p < .05 or p < .01 when compared with group Sr0; #p < .05 or p < .01 when compared with group Sr30; &p < .05 or p < .01 when compared with group Sr60
Observation of morphology and growth of MC3T3‐E1 cells on different Sr‐containing coatings after 24 h culture. (A) Cell observation under SEM at a magnification of ×1000, ×5000, and ×10,000, respectively. (B) Cell observation under fluorescent microscope at a magnification of ×600. F‐Actin is stained with fluorescein isothiocyanate‐conjugated phalloidin (FITC‐phalloidin) (green) and the cell nuclei are stained with propidium iodide (PI) (red). (c and d) Quantitative analysis of average cell size and percentage of cell area on different coatings. *p < .05 or p < .01 when compared with group Sr0; #p < .05 or p < .01 when compared with group Sr30; &p < .05 or p < .01 when compared with group Sr60
Strontium (Sr) is the most common element introduced into TiO2 coatings to strengthen the osteogenic property of titanium implants. However, the optimal Sr content and its effect on osteogenic and physicochemical properties of the coatings need to be clarified. In the current study, TiO2 microporous coatings with different contents of Sr (9.64–21.25 wt %) and silver (Ag) (0.38–0.75 wt %) were prepared via micro‐arc oxidation technique. Sr contents did not change physicochemical properties of the coatings, including surface microstructure, micropore size and distribution, phase composition, roughness and hydrophilicity. Meanwhile, higher Sr contents (18.23–21.25 wt %) improved cytocompatibility, proliferation and alkaline phosphatase (ALP) activity of preosteoblasts, even the coatings underwent 30 days' PBS immersion. Furthermore, higher Sr contents facilitated preosteoblast growth and spreading, which are essential for their proliferation and osteogenic differentiation. Therefore, it is promising to incorporate higher Sr content (18.23–21.25 wt %) within TiO2 microporous coatings to improve their osteogenic capability.
Bisphosphonates are drugs that are used to treat osteoporosis that causes the low mineral density of the bones. These drugs can be delivered in several ways, but each method has disadvantages. Materials with high potential as carriers of these drugs are zeolites with divalent ions. The aim of this study was to investigate the effect of divalent cations (calcium, magnesium, zinc) and drug type (risedronate, zoledronate) on sorption and release of the drug for osteoporosis. It was proved that drug sorption occurs on all zeolites presented in this work. Risedronate sorption was highest in zinc zeolite and lowest in calcium zeolite. In the case of zoledronate, sorption was most effective in magnesium zeolite and the least effective in zinc zeolite. Very large differences in drug release profiles were also observed. Risedronate was released several times longer than zoledronate. The diversity of the results indicates that the examined materials can be used in different types of drug delivery systems. They can be used, for example, intravenously or in the form of implants due to the different release profiles. Furthermore, the proposed carriers also release magnesium and calcium ions which are used in the prevention of osteoporosis, and zinc ions which have antibacterial properties.
Integration of native bone into orthopedic devices is a key factor in long‐term implant success. The material‐tissue interface is generally accepted to consist of a hydroxyapatite layer so bioactive materials that can spontaneously generate this hydroxyapatite layer after implantation may improve patient outcomes. Per the ISO 22317:2014 standard, “Implants for surgery – In vitro evaluation for apatite‐forming ability of implant materials,” bioactivity performance statements can be assessed by soaking the material in simulated body fluid (SBF) and evaluating the surface for the formation of a hydroxyapatite layer; however, variations in test methods may alter hydroxyapatite formation and result in false‐positive assessments. The goal of this study was to identify the effect of SBF formulation on bioactivity assessment. Bioglass® (45S5 and S53P4) and non‐bioactive Ti‐6Al‐4V were exposed to SBF formulations varying in calcium ion and phosphate concentrations as well as supporting ion concentrations. Scanning electron microscopy and X‐ray powder diffraction evaluation of the resulting hydroxyapatite layers revealed that SBF enriched with double or quadruple the calcium and phosphate ion concentrations increased hydroxyapatite crystal size and quantity compared to the standard formulation and can induce hydroxyapatite crystallization on surfaces traditionally considered non‐bioactive. Altering concentrations of other ions, for example, bicarbonate, changed hydroxyapatite induction time, quantity, and morphology. For studies evaluating the apatite‐forming ability of a material to support bioactivity performance statements, test method parameters must be adequately described and controlled. It is unclear if apatite formation after exposure to any of the SBF formulations is representative of an in vivo biological response. The ISO 23317 standard test method should be further developed to provide additional guidance on apatite characterization and interpretation of the results.
Representative images and means ± SD (in degrees) of contact angle measurements of machining (left) and polishing (right) surfaces after treatment with self‐etching ceramic primer. Different superscript letters indicate statistically significant differences (t test; p < .05)
Representative scanning electron microscope (SEM) images (200× magnification) of machining (left) and polishing (right) groups. The micrographs depicted a rougher surface for machining
Representative scanning electron microscope (SEM) micrographics of fractographical examination at 200× and 1000× magnification. The (*) indicate that all fracture origins are located at the tensile side. M depicts a failure origin at a surface defect nearby a material intrinsic pore; P presents a failure origin not related to any specific surface characteristic, suggesting high energy accumulated before failure; MH, ML, PH and PL shows failures originating in the cement layer and propagating through the ceramic; ML present a large bubble in cement, associated to the failure origin, and a line indicating that cement is detaching from ceramic, which is also depicted in the PH specimen. Arrows indicate fracture propagation direction (hackles)
Scanning electron microscope (SEM) micrographs (10,000×) illustrating the intaglio surface between the ceramic and the cement, where it notices the intimacy achieved in all conditions explored
This study evaluated the effect of resin cement coating with high and low viscosities on the flexural fatigue strength of machined lithium disilicate glass‐ceramic. Discs (IPS e.max CAD; Ivoclar Vivadent) were prepared and divided according to the surface condition (machining [M]—CEREC inLab; and polishing [P]—laboratory procedures), resin cement coating (with or without), and cement viscosity (high [H] and low [L]). The ceramic bonding surface was etched/primed by a one‐step primer application followed by resin cement application (Variolink N base + high or low viscosity catalyst; Ivoclar Vivadent). Biaxial flexural fatigue strength was evaluated on a piston‐on‐three‐ball set by the step‐test method (n = 15) (initial stress: 60 MPa; incremental steps: 20 MPa; 10,000 cycles/step, at 20 Hz). Weibull statistics were used for fatigue data. Contact angle, topographic, and fractographic analysis were also performed. Machining produced statistically lower contact angle than polishing and a significant detrimental effect on the fatigue behavior (σ0M = 247.2 [246.9–268.3]; σ0P = 337.4 [297.8–382.4]). Machined groups followed by resin cement coating (σ0MH = 297.9 [276.0–321.5]; σ0Ml = 301.2 [277.1–327.4]) behaved similarly to the polished and coated groups (σ0PH = 342.0 [308.9–378.5]; σ0PL = 357.3 [324.7–393.1]), irrespective of the cement viscosity. Therefore, cement coating has able to revert the detrimental effects of the machining on the fatigue strength of lithium disilicate glass‐ceramic. High and low viscosity cements behaved similarly in the improvement of CAD–CAM lithium disilicate fatigue strength.
Transmission electron microscopy (TEM) images (A) and X‐ray diffraction spectra (XRD) pattern (B) of as‐synthesized cerium oxide (CeO2) NPs.
Representative histograms of annexin V‐FITC fluorescence. Erythrocytes exposed to various concentrations of cerium oxide (CeO2) nanoparticles were stained with annexin V‐FITC for assessing eryptosis. Cerium oxide (CeO2) NP1 at a concentration of 250 mg/L were found to stimulate eryptosis.
DNA Cleavage activity of cerium oxide (CeO2) nanoparticles. (Lane 1) pBR 322 DNA, (Lane 2) pBR 322 DNA + 125 mg/L CeO2 NP1, (Lane 3) pBR 322 DNA + 250 mg/L of CeO2 NP1, (Lane 4) pBR 322 DNA + 500 mg/L of CeO2 NP1, (Lane 5) pBR 322 DNA + 125 mg/L CeO2 NP2, (Lane 6) pBR 322 DNA + 250 mg/L of CeO2 NP2, (Lane 7) pBR 322 DNA + 500 mg/L of CeO2 NP2.
Microbial cell viability
Biofilm inhibition
The control over bacterial diseases requires the development of novel antibacterial agents. The use of antibacterial nanomedicines is one of the strategies to tackle antibiotic resistance. The study was designed to assess the antimicrobial activity of cerium oxide (CeO2) nanoparticles (NP) of two different sizes (CeO2 NP1 [1–2 nm] and CeO2 NP2 [10–12 nm]) and their cytotoxicity towards eukaryotic cells. The antimicrobial activity, effects of nanoparticles on DNA cleavage, microbial cell viability, and biofilm formation inhibition were analyzed. The impact of cerium oxide nanoparticles on eryptosis of erythrocytes was estimated using annexin V staining by flow cytometry. The newly synthesized CeO2 NP1 and CeO2 NP2 displayed moderate antimicrobial activities. CeO2 NP1 and CeO2 NP2 exhibited single‐strand DNA cleavage ability. CeO2 NPs were found to show 100% microbial cell viability inhibition at a concentration of 500 mg/L. In addition, CeO2 NP1 and CeO2 NP2 inhibited the biofilm formation of S. aureus and P. aeruginosa. Larger cerium oxide nanoparticles were found to be less toxic against erythrocytes compared with the smaller ones. CeO2 nanoparticles demonstrate moderate antimicrobial activity and low cytotoxicity towards erythrocytes, which make them promising antibacterial agents.
With the ripening of 3D printing technology and the discovery of a variety of printable materials, 3D‐printed vascular stents provide new treatment options for patients with angiocardiopathy. Bioresorbable stent not only combines the advantages of metallic stent and drug‐coated balloon, but also avoids the disadvantages of them. 3D printing is also an economical and efficient way to produce stents and makes it possible to construct complex structures. In this study, stents made from poly(l‐lactic acid) (PLLA), poly(ε‐caprolactone) (PCL) and poly(l‐lactide‐co‐caprolactone) (PLCL) were manufactured by 3D printing and evaluated for radial strength, crystallinity and molecular weight. PLCL copolymerized by different proportions of lactic acid and caprolactone showed different mechanical and degradation properties. This demonstrated the potential of 3D printing as a low‐cost and high throughput method for stent manufacturing. The PLLA and PLCL 95/5 stents had similar mechanical properties, whereas PLCL 85/15 and PCL stents both had relatively low radial strength. In general, PLCL 95/5 had a faster degradation rate than PLLA. These two materials were made into peripheral vascular bioresorbable scaffolds (BRS) and further studied by additional bench testing. PLCL 95/5 peripheral BRS had superior mechanical properties in terms of flexural/bending fatigue and compression resistance.
Human hair proteins are recognized for their intrinsically high cysteine content. They can be solubilized while preserving their highly reductive thiol groups for free radical scavenging applications. The presence of aromatic and nucleophilic amino acids such as methionine, serine, phenylalanine, and threonine further contribute to the antioxidative potential of this material. Herein, utilizing the DPPH (2,2‐diphenyl‐1‐picrylhydrazyl) and acellular 2′,7′‐dichlorodihydrofluorescein diacetate (H2DCFDA) assays, keratins are demonstrated to possess the highest radical scavenging activity among the studied hair proteins. Consequently, protection against hydrogen peroxide‐induced oxidative stress in human dermal fibroblasts (HDFs) cultured in human hair keratin supplemented media is demonstrated. Quenching of reactive oxygen species in the HDF is observed using the CellROX Green dye and the expression levels of antioxidant (HMOX1, SOD2, GPX1) and tumor suppressor (TP53) genes is analyzed using qPCR. Collectively, this study presents further evidence and demonstrates the in vitro application potential of hair proteins, especially keratins, as an antioxidizing supplement.
Numerous biomaterials have been developed for application in blood‐contacting medical devices to prevent thrombosis; however, few materials have been applied to full‐scale devices and evaluated for hemocompatibility under clinical blood flow conditions. We applied a dual‐action slippery liquid‐infused (LI) nitric oxide (NO)‐releasing material modification (LINO) to full‐scale blood circulation tubing for extracorporeal lung support and evaluated the tubing ex vivo using swine whole blood circulated for 6 h at a clinically relevant flow. LINO tubing was compared to unmodified tubing (CTRL) and isolated LI and NO‐releasing modifications (n = 9/group). The primary objective was to evaluate safety and blood compatibility of this approach, prior to progression to in vivo testing of efficacy in animal models. The secondary objective was to evaluate coagulation outcomes relevant to hemocompatibility. No untoward effects of the coating, such as elevated methemoglobin fraction, were observed. Additionally, LINO delayed platelet loss until 6 h versus the reduction in platelet count in CTRL at 3 h. At 6 h, LINO significantly reduced the concentration of platelets in an activated P‐selectin expressing state versus CTRL (32 ± 1% decrease, p = .02). Blood clot deposition was significantly reduced on LINO blood pumps (p = .007) and numerically reduced on tubing versus CTRL. Following blood exposure, LINO tubing continued to produce a measurable NO‐flux (0.20 ± 0.06 × 10⁻¹⁰ mol cm⁻² min⁻¹). LINO is a potential solution to reduce circuit‐related bleeding and clotting during extracorporeal organ support, pending future extended testing in vivo using full‐scale extracorporeal lung support devices.
Rigid spinal fusion with instrumentation has been widely applied in treating degenerative spinal disorders and has shown excellent and stable surgical results. However, adjacent segment pathology or implants' loosening could be problematic due to the spine's segmental fusion. Therefore, this study verified a novel concept for posterior stabilization with polyethylene inserts inside a pedicle screw assembly using bone models. We observed that although the gripping capacity of the dynamic pedicle screw system using a tensile and compression tester was less than half that of the rigid pedicle screw system, the flexion‐extension moment of the dynamic pedicle screws was significantly lower than that of the rigid pedicle screws. Furthermore, while the bending force of the rigid pedicle screw assembly increased linearly with an increase in the bending angle throughout the test, that of the dynamic pedicle screw assembly also increased linearly until a bending angle of 2.5° was reached. However, this angle decreased at a bending angle of more than 2.5°. Additionally, the fatigue test of 1.0 × 10⁶ cycles showed that the pull‐out force of the dynamic pedicle screws from two different polyurethane foam blocks was significantly higher than that of the rigid pedicle screws. Therefore, based on our results, we propose that the device can be applied in clinical cases to reduce screw loosening and adjacent segment pathology.
In synthetic fabrication, the process parameters decide the growth nucleation, phase translation, and the evolution of morphological facets of nanostructured materials. This work demonstrates the formation of different crystallographic phases of calcium phosphate by the influence of pH from acidic to alkaline conditions and also investigated their bone regeneration, protein adsorption, and pro‐angiogenic properties. Present results illustrate that the alteration of pH is the crucial factor for the synthesis of calcium phosphate (CP) phases. The structural analysis reveals the monetite (CaHPO4) phase with a triclinic crystal system for pH 5, dual‐phase of monetite combined with hydroxyapatite at the neutral pH 7, and pure phase of hydroxyapatite (Ca10[PO4]6OH2) with hexagonal structure at pH 10. Microscopic analysis portrays the cubic and rod‐like morphologies by changing the pH values. FTIR and RAMAN spectroscopic analyses confirm the stretching, bending, and vibrational modes of dominant phosphate groups of different CP phases. Further, the biocompatibility of the prepared CP phases was examined by hemolysis assay, which showed less than 2% of lysis and enhanced cell viability. Moreover, the bioactivity study revealed rapid mineralization and a higher protein adsorption rate for the monetite CP phase (M‐CP). Subsequently, the chick embryo angiogenesis assay elucidated 33% higher neovascularization for M‐CP compared with the other two CP phases. The fabricated M‐CP nanostructure constitutes a promising candidate for biomedical applications. Schematic illustration of pro‐angiogenic property of calcium phosphate based nanostructures
(A) XRD patterns of Fe3O4, Fe3O4@PEI and Fe3O4@PEI@FA. (B) SEM, (C) element mappings and (D) TEM images of Fe3O4 sample.
TEM images and nanosphere size analysis charts of (A–C) Fe3O4, (D–F) Fe3O4@PEI and (G–I) Fe3O4@PEI@FA.
(A) Magnetization hysteresis loops, (B) hydrodynamic size of Fe3O4, Fe3O4@PEI and Fe3O4@PEI@FA. (C) Heating curves of all samples with the Fe concentration of 0.25 mg/mL. (D) All calculated SAR values of Fe3O4, Fe3O4@PEI and Fe3O4@PEI@FA measured at 0.05, 0.1 and 0.25 mg/mL, respectively.
Biocompatibility of Fe3O4@PEI and Fe3O4@PEI@FA for (A) Hela, (B) SKOV3, (C) HEC‐1‐A and (D) NIH3T3 cells.
Live/dead assay on Hela, NIH3T3, HEC‐1‐A, SKOV3 cells incubated with Fe3O4@PEI@FA nanospheres with different concentration: (A–D) control; (E–H) 12.5 μg/mL; (I–L) 250 μg/mL, respectively. The scale bar indicates 100 μm.
Recent studies have highlighted the development prospects of magnetic hyperthermia in cancer therapy. A few studies on the application of Fe3O4 nanospheres for the magnetic hyperthermia of gynecological malignancies have achieved certain efficacy, but there was no visible progress currently. In this work, Fe3O4 nanospheres modified with polyetherimide (PEI) and folic acid (FA) were synthesized using a hydrothermal method for possible utility in biocompatible and active tumor‐targeting magnetic induction hyperthermia. The PEI‐ and FA‐coated Fe3O4 nanospheres showed high crystallinity, well‐dispersed spherical structures and ideal Ms value. As a result, the designed Fe3O4@ PEI@FA nanospheres achieved higher specific absorption rate (SAR) values at 360 kHz and 308 Oe, as well as excellent biocompatibility in Hela, SKOV3, HEC‐1‐A and NIH3T3 cells. These nanospheres can be used as an optimal heating agent for the magnetic hyperthermia treatment of gynecological cancers.
Developing dental materials for the prevention of remineralization or demineralization is important for high‐risk caries patients. This study aimed to evaluate the physicochemical and microbiological effects of adding 45S5 bioglass to resin‐modified glass ionomer cement (RMGIC). Samples belonged to the following groups: GIC: conventional glass ionomer cement (Vitro Fil), RMGIC: resin‐modified GIC (Vitro Fil LC), and RMGIC/45S5: RMGIC with 10% (wt %) of 45S5. Changes in pH and release of fluoride, calcium, and phosphorus ions under acidic (pH 4) and neutral (pH 7) pH conditions were evaluated. Antibacterial activity was verified based on colony‐forming units. Material sorption and solubility were analyzed after bacterial exposure. After 28 days, the bioactivity of the materials was evaluated using scanning electron microscopy/energy dispersive X‐ray spectroscopy (SEM/EDS). Analysis of variance, post hoc Scheffe, and Tukey (α = 0.05) tests were employed for statistical analysis. RMGIC/45S5 showed higher alkalization activity, calcium release at pH 4 and 7, and sorption than GIC and RMGIC (p < .05). Release of phosphorus and fluoride at pH 4 and 7 was higher for GIC than that for RMGIC and RMGIC/45S5 (p < .05). RMGIC/45S5 showed higher values than RMGIC (p < .05). However, antibacterial activity did not differ among the groups. Precipitates of calcium and phosphorus were visualized in RMGIC/45S5 samples via SEM/EDS. These results indicate that the RMGIC/45S5 promotes alkalization and increases the release of calcium, phosphorus, and fluoride ions, resulting in precipitate deposition rich in calcium and phosphorus, thereby being a promising option to improve the bioactivity of RMGIC.
This study aimed to investigate the appropriate size of scaffold implantation on stress distribution and evaluate its mechanical and biomechanical properties considering hydrolysis. The meniscus acts as a load distribution in the knee, and its biomechanical properties are essential for the development of the PGA scaffold. We established a novel meniscal scaffold, which consists of polyglycolic acid (PGA) covered with L‐lactide‐ε‐caprolactone copolymer (P[LA/CL]). After 4 weeks of hydrolysis, the scaffold had a 7% volume reduction compared to the initial volume. In biomechanical tests, the implantation of scaffolds 20% larger than the circumferential and vertical defect size results in greater contact stress than the intact meniscus. In the mechanical evaluation associated with the decomposition behavior, the strength decreased after 4 weeks of hydrolysis. Meanwhile, in the biomechanical test considering hydrolysis, contact stress and area equivalent to intact were obtained after 4 weeks of hydrolysis. In conclusion, the implantation of the PGA scaffold might be a useful alternative to partial meniscectomy in terms of mechanical properties, and the PGA scaffold should be implanted up to 20% of the defect size.
Current standards in bone‐facing implant fabrication by metal 3D (M3D) printing require post‐manufacturing modifications to create distinct surface properties and create implant microenvironments that promote osseointegration. However, the biological consequences of build parameters and surface modifications are not well understood. This study evaluated the relative contributions of build parameters and post‐manufacturing modification techniques to cell responses that impact osseointegration in vivo. Biomimetic testing constructs were created by using a M3D printer with standard titanium–aluminum–vanadium (Ti6Al4V) print parameters. These constructs were treated by either grit‐blasting and acid‐etching (GB + AE) or GB + AE followed by hot isostatic pressure (HIP) (GB + AE, HIP). Next, nine constructs were created by using a M3D printer with three build parameters: (1) standard, (2) increased hatch spacing, and (3) no infill, and additional contour trace. Each build type was further processed by either GB + AE, or HIP, or a combination of HIP treatment followed by GB + AE (GB + AE, HIP). Resulting constructs were assessed by SEM, micro‐CT, optical profilometry, XPS, and mechanical compression. Cellular response was determined by culturing human bone marrow stromal cells (MSCs) for 7 days. Surface topography differed depending on processing method; HIP created micro‐/nano‐ridge like structures and GB + AE created micro‐pits and nano‐scale texture. Micro‐CT showed decreases in closed pore number and closed porosity after HIP treatment in the third build parameter constructs. Compressive moduli were similar for all constructs. All constructs exhibited ability to differentiate MSCs into osteoblasts. MSCs responded best to micro−/nano‐structures created by final post‐processing by GB + AE, increasing OCN, OPG, VEGFA, latent TGFβ1, IL4, and IL10. Collectively these data demonstrate that M3D‐printed constructs can be readily manufactured with distinct architectures based on the print parameters and post‐build modifications. MSCs are sensitive to discrete surface topographical differences that may not show up in qualitative assessments of surface properties and respond by altering local factor production. These factors are vital for osseointegration after implant insertion, especially in patients with compromised bone qualities.
Amniotic membrane (AM) is a naturally derived biomaterial with biological and mechanical properties important to Ophthalmology. The epithelial side of the AM promotes epithelialization, while the stromal side regulates inflammation. However, not all AMs are equal. AMs undergo different processing with resultant changes in cellular content and structure. This study evaluates the effects of sidedness and processing on human corneal epithelial cell (HCEC) activity, the effect of processing on HCEC inflammatory response, and then a case study is presented. Three differently processed, commercially available ocular AMs were selected: (1) Biovance®3L Ocular, a decellularized, dehydrated human AM (DDHAM), (2) AMBIO2®, a dehydrated human AM (DHAM), and (3) AmnioGraft®, a cryopreserved human AM (CHAM). HCECs were seeded onto the AMs and incubated for 1, 4 and 7 days. Cell adhesion and viability were evaluated using alamarBlue assay. HCEC migration was evaluated using a scratch wound assay. An inflammatory response was induced by TNF‐α treatment. The effect of AM on the expression of pro‐inflammatory genes in HCECs was compared using quantitative polymerase chain reaction (qPCR). Staining confirmed complete decellularization and the absence of nuclei in DDHAM. HCEC activity was best supported on the stromal side of DDHAM. Under inflammatory stimulation, DDHAM promoted a higher initial inflammatory response with a declining trend across time. Clinically, DDHAM was used to successfully treat anterior basement membrane dystrophy. Compared with DHAM and CHAM, DDHAM had significant positive effects on the cellular activities of HCECs in vitro, which may suggest greater ocular cell compatibility in vivo.
Collagen‐based scaffolds reveals promising to repair severe skin defects. The mechanical strength of collagen‐based scaffold (CCS) limited its clinical application. Embedding poly(lactic‐co‐glycolic) acid (PLGA) knitted mesh into CCS improves the mechanical strength of the scaffold. This study was conducted to optimize the configuration of PLGA knitted mesh‐collagen‐chitosan scaffold (PCCS), and explore possible mechanisms. PLGA knitted mesh was embedded in CCS through freeze‐drying method. With the PLGA knitted mesh located at the bottom, middle, or both bottom and top layers of the CCS, three kinds of PCCS were developed. A full‐thickness skin wound model was established in Sprague Dawley rats to evaluate the therapeutic effects of different PCCS against CCS. The properties and healing effect of the scaffolds were investigated. Several growth factors and chemotactic factors, that is, VEGF, PDGF, CD31, α‐SMA, TGF‐β1, and TGF‐β3 were analyzed and evaluated. Re‐epithelialization and angiogenesis were observed in all animal groups with the treatment of three kinds of PCCS scaffolds and the CCS scaffold (control). The protein and gene expression of VEGF, PDGF, CD31, α‐SMA, TGF‐β1, and TGF‐β3 showed different dynamics at different time points. Based on the healing effects and the expression of growth factors and chemotactic factors, scaffold with the PLGA knitted mesh located at the bottom layer of the CCS demonstrated the best healing effect and accelerated re‐epithelialization and angiogenesis among all the scaffolds evaluated. PCCS with the PLGA mesh located in the bottom layer of the scaffold accelerated wound healing by creating a more supportive environment for re‐epithelialization and angiogenesis.
Participant flow diagram describing the original five study groups based on the different head‐cup articulations and the final three groups based on head material (stainless steel, CoCrMo, and Oxinium). Exclusions after 10 years follow‐up are sorted after revision causes (infection or aseptic loosening) and reasons for drop out (deceased or lost to follow‐up). The gender distribution, age and Harris Hip Score (median and range) in the three study groups are specified
(A) Charnley flanged 40 monoblock, oval, 316 L stainless steel, matte surface (Ra 0.8 μm) femoral stem with a 22.2 mm head, which articulated with a Charnley Ogee UHMWPE acetabular cup. (B) Spectron EF CoCrMo femoral stem with a 28 mm CoCrMo modular femoral head, retrieved from study case n° 819, with abrasive marks on the stem‐cement interface, mainly on the posterior‐distal‐medial side. The collared Spectron EF stem was fabricated with a matte distal surface (Ra 0.7 μm) and a grit blasted roughened surface (Ra 7.3 μm) on the proximal third of the stem. The neck and collar are highly polished.¹⁵ The stem used in this RCT was supplied with three tantalum markers, one of which was attached to a cone in the neck, the second in the medial side of the collar and the third on the distal tip of the stem. (C) CoCrMo 28 mm femoral head (left) and Oxinium 28 mm femoral head (right). Spectron EF stem taper size 12/14, standard offset (in the middle). (D) Reflection All‐Poly UHMWPE cup.
Boxplot of blood metal ion levels (μg/L) for Cr, Co, Zr, and Ni, grouped on head material. Horizontal lines inside the boxes indicates median level. Whiskers represents min‐max values (range). SS, stainless steel
The use of inert head materials such as ceramic heads has been proposed as a method of reducing wear and corrosion products from the articulating surfaces in total hip arthroplasty, as well as from the stem‐head taper connection. The aim of the present study was to compare the blood metal ion levels in patients with Oxinium and CoCrMo modular femoral heads, as well as monoblock stainless steel Charnley prostheses at 10 years postoperatively. The 150 patients with osteoarthritis of the hip joint included in a randomized clinical trial were grouped according to femoral head material. One group (n = 30) had received the Charnley monoblock stainless steel stem (DePuy, UK). The other patients (n = 120) received a Spectron EF CoCrMo stem with either a 28 mm CoCrMo or Oxinium modular head (Smith & Nephew, USA). After 10 years, 38 patients had withdrawn, 19 deceased, 7 revised due to aseptic loosening and 5 revised due to infection. The 81 patients with median age of 79 years (70–91) were available for whole blood metal ion analysis. The levels of Co, Cr, Ni and Zr in the blood were generally low with all the head materials (medians <0.3 micrograms/L) and no statistical difference between the groups were found (p = .2–.8). Based on the low blood metal ion values in our study groups, no indication of severe trunnion corrosion in patients with CoCrMo heads was observed, neither was there any beneficial reduction in metal ion exposure with the Oxinium femoral heads.
Confined compression specimens used in this study. Shown are (A) schematic showing the composite and epoxy ring for confined compression by the plunger, (B) the plunger, base, epoxy ring, and composite specimen (left to right), and (C) fully assembled confined compression specimen.
Predicted aqueous saturation of compule‐sized composite as a function of time. Shone are predicted saturation curves of DI, and AS in Fil and AEL composites
Although salivary liquid can degrade constituents in resin‐based dental composites in short‐term incubations, there is a knowledge gap on how longer‐term aging impacts their bulk strength. We address this through extended aging studies with resin‐based dental composites in different environments. Two commercial composites (FIL and AEL) were aged aseptically at 37°C in air (A, control), artificial saliva (AS), and esterase enzyme amended AS (EAS). Diametral and pushout strength were measured after periods of 120–180 days. At 120 days, the diametral strength of composites aged in air was 69.9 ± 11.0 and 57.7 ± 3.31 MPa in FIL and AEL, respectively. These were significantly greater compared to composites aged in AS (32.1 ± 7.01 and 46.2 ± 9.38 MPa in FIL and AEL, respectively) or EAS (36.7 ± 8.49 and 43.5 ± 5.51 MPa in FIL and AEL, respectively). In contrast, pushout strength for both composites were smaller in A compared to those aged in AS and EAS, results attributed to AS absorption and polymer expansion. No significant change in either diametral or pushout strength occurred after 120 days. There was no significant difference between aging in AS and EAS, suggesting that esterase did not significantly decrease the bulk material strength to a greater extent than AS under the test conditions. Aqueous diffusivities for the composites ranged from 8.4 to 11 × 10⁻¹³ m²/s, with associated porosities ranging from 0.06% to 0.10%. These results indicate that saturation of a typical dental composite occurs over a time frame of 4–5 months, longer than typical aging studies. Together, the results demonstrate the importance of aging time on composite strength.
Numerous studies have examined the effect of serum and blood proteins on the general corrosion of metallic biomedical materials. However, it is unclear whether proteins have any effect in the case of CoCr alloys, particularly at physiological concentrations. In this work, potentiodynamic polarization and electrochemical impedance spectroscopy were used to investigate the electrochemical behavior of Co‐35Ni‐20Cr‐10Mo in PBS, PBS with albumin at a concentration (36 g/L) representative of serum, and bovine serum. The corrosion current density (icorr) for the CoNiCrMo was changed little by the addition of serum‐level albumin to PBS but it was more than halved in serum. Albumin and serum had little effect on the oxide thickness obtained using impedance spectroscopy, but they increased the effective resistance of the oxide consistent with the changes in icorr. The potentiodynamic and impedance results indicate that the general corrosion behavior of the CoNiCrMo in serum is affected more by other proteins such as globulin rather than by albumin alone. Furthermore, the proteins in serum are beneficial with regard to the general corrosion behavior of the alloy, suggesting that the proteins act predominantly as inhibitors rather than as corrosion promoters that limit phosphate adsorption and associated inhibition.
Generating electrospun mats with aligned fibers and obtaining neurite extension in the aligned fiber direction could provide hope for fabricating nerve guidance conduits or wraps through an easy method. The growing interest in generating electrospun mats with aligned fibers for tissue engineering is looking for simple methods to generate the same. Here, in this study, ethylene vinyl alcohol copolymer (EVAL) chains were complexed with silver ions (Ag+) to generate aligned fibers during the electrospinning process. The fibers thus produced were subjected to physico‐chemical characterization and biological studies to ensure their properties and to examine whether suitable for neuronal cell attachment and neurite extension that may be useful in making nerve guidance conduits or wraps. The presence of silver ions and its complex formation with –OH of EVAL has been confirmed with EDX and XPS analysis respectively. The alignment of fibers was visualized from SEM analysis and confirmed using directionality analysis using Fiji‐ImageJ software. Mechanical properties done with dumbbells punched out in longitudinal and transverse directions also substantiated the alignment of fibers. The results obtained from direct contact, MTT, and live/dead assay showed the cells are viable on the material. From the actin staining and immunostaining assays, it was evident that the PC12 cells could attach and extend their neurites in an aligned manner on the fibers. The maximum neurite extension was up to 200 μm in length. These properties of electrospun EVAL‐Ag mat with aligned fibers indicated that it could be developed as a biocompatible nerve guidance conduit or wrap. Neurite extension on aligned fibers fabricated from silver ion complexed Ethylene vinyl alcohol copolymer (EVAL).
This article presents silica nanoparticles for the sustained release of AMACR antibody‐conjugated and free doxorubicin (DOX) for the inhibition of prostate cancer cell growth. Inorganic MCM‐41 silica nanoparticles were synthesized, functionalized with phenylboronic acid groups (MCM‐B), and capped with dextran (MCM‐B‐D). The nanoparticles were then characterized using Fourier‐transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, zeta potential analysis, nitrogen sorption, X‐ray diffraction, and thermogravimetric analysis, before exploring their potential for drug loading and controlled drug release. This was done using a model prostate cancer drug, DOX, and a targeted prostate cancer drug, α‐Methyl Acyl‐CoA racemase (AMACR) antibody‐conjugated DOX, which attaches specifically to AMACR proteins that are overexpressed on the surfaces of prostate cancer cells. The kinetics of sustained drug release over 30 days was then studied using zeroth order, first order, second order, Higuchi, and the Korsmeyer–Peppas models, while the thermodynamics of drug release was elucidated by determining the entropy and enthalpy changes. The flux of the released DOX was also simulated using the COMSOL Multiphysics software package. Generally, the AMACR antibody‐conjugated DOX drug‐loaded nanoparticles were more effective than the free DOX drug‐loaded formulations in inhibiting the growth of prostate cancer cells in vitro over a 96 h period. The implications of the results are then discussed for the development of drug‐eluting structures for the localized and targeted treatment of prostate cancer.
Hydrogel materials are promising candidates in cartilage tissue engineering as they provide a 3D porous environment for cell proliferation and the development of new cartilage tissue. Both the mechanical and transport properties of hydrogel scaffolds influence the ability of encapsulated cells to produce neocartilage. In photocrosslinkable hydrogels, both of these material properties can be tuned by changing the crosslinking density. However, the interdependent nature of the structural, physical and biological properties of photocrosslinkable hydrogels means that optimizing composition is typically a complicated process, involving sequential and/or iterative steps of physiochemical and biological characterization. The combinational nature of the variables indicates that an exhaustive analysis of all reasonable concentration ranges would be impractical. Herein, response surface methodology (RSM) was used to efficiently optimize the composition of a hybrid of gelatin‐methacryloyl (GelMA) and hyaluronic acid methacryloyl (HAMA) with respect to both mechanical and transport properties. RSM was employed to investigate the effect of GelMA, HAMA, and photoinitiator concentration on the shear modulus and diffusion coefficient of the hydrogel membrane. Two mathematical models were fitted to the experimental data and used to predict the optimum hydrogel composition. Finally, the optimal composition was tested and compared with the predicted values.
The development of vascularized scaffolds remains one of the major challenges in tissue engineering, and co‐culturing with endothelial cells is known as one of the possible approaches for this purpose. In this approach, optimization of cell culture conditions, scaffolds, and fabrication techniques is needed to develop tissue equivalents that will enable in vitro formation of a capillary network. Prevascularized equivalents will be more physiologically comparable to the native tissues and potentially prevent insufficient vascularization after implantation. This study aimed to culture human umbilical vein endothelial cells (HUVECs), alone or in co‐culture with fibroblasts, on collagen scaffolds prepared by simple fabrication approaches for in vitro prevascularization. Different concentrations and ratios of HUVECs and fibroblasts seeded on collagen gel and sponge scaffolds under several culture conditions were examined. Cell viability, scaffolds morphology, and structure were analyzed. Collagen gel scaffolds showed good cell proliferation and viability, with higher proliferation rates for cells cultured in a 2:1 (fibroblasts: HUVECs) ratio and kept in endothelial cell growth medium. However, these matrices were unable to support endothelial cell sprouting. Collagen sponges were highly porous and showed good cell viability. However, they became fragile over time in culture, and they still lack signs of vascularization. Collagen scaffolds were a good platform for cell growth and viability. However, under the experimental conditions of this study, the HUVEC/fibroblast‐seeded scaffolds were not suitable platforms to generate in vitro prevascularized equivalents. Our findings will be a valuable starting point to optimize culture microenvironments and scaffolds during fabrication of prevascularized scaffolds.
The addition of dopants in biomaterials has emerged as a critical regulator of bone formation and regeneration due to their imminent role in the biological process. The present work evaluated the role of strontium (Sr) and magnesium (Mg) dopants in brushite cement (BrC) on in vivo bone healing performance in a rabbit model. Pure, 1 wt% SrO (Sr‐BrC), 1 wt% MgO (Mg‐BrC), and a binary composition of 1.0 wt% SrO + 1.0 wt% MgO (Sr + Mg‐BrC) BrCs were implanted into critical‐sized tibial defects in rabbits for up to 4 months. The in vivo bone healing of three doped and pure BrC samples was examined and compared using sequential radiological examination, histological evaluations, and fluorochrome labeling studies. The results indicated excellent osseous tissue formation for Sr‐BrC and Sr + Mg‐BrC and moderate bone regeneration for Mg‐BrC compared to pure BrC. Our findings indicated that adding small amounts of SrO, MgO, and binary dopants to the BrC can significantly influence new bone formation for bone tissue engineering.
The goals of the study were to investigate the effects on bone bioactivity of a titanium dioxide layer formed by hydrothermal oxidation of a titanium surface with hydrogen peroxide (H2O2) and loading with fibroblast growth factor‐2 (FGF‐2) in vitro and in vivo. Ti‐6Al‐4V discs were hydrothermally oxidized with H2O2 and then loaded with FGF‐2. After cytotoxicity testing, Ti‐6Al‐4V mini‐implants were subjected to the same treatment, and their osteogenic potential was evaluated histologically in a rat model. H2O2 hydrothermal oxidation resulted in a dense porous network structure and hydrophilic changes, which improved retention of FGF‐2. Morphologically, the cell density was higher, cell elongation was more pronounced, and the cell adhesion area was significantly higher in FGF‐2‐loaded cells than in those without FGF‐2. In a cell proliferation assay using mouse osteoblast‐like cells, absorbance tended to increase over time, especially in the FGF‐2 group after 7 and 14 days, and in a bone differentiation assay based on ALP activity, there was a significant increase in the FGF‐2 group after 14 days. In the rat model, H2O2 hydrothermal oxidation and FGF‐2 loading both resulted in more laminar bone tissue in the bone marrow around the mini‐implant. These results suggest that titanium surface functionalization by H2O2 hydrothermal oxidation and FGF‐2 may promote initial cell adhesion, proliferation, and osteodifferentiation, and enhance bone bioactivity. These effects all contribute to early bonding of an implant with the surrounding bone.
Hydrogel materials provide an extremely promising group of materials that can find an increasingly wide range of use in treating urinary system conditions due to their unique properties. The present review describes achievements to date in terms of the use and development prospects of hydrogel materials applications in the treatment and reconstruction of the urinary system organs, which among others include: hydrogel systems of intravesical drug delivery, ureteral stents design, treatment of vesicoureteral reflux, urinary bladder and urethral defects reconstruction, design of modern urinary catheters and also solutions applied in urinary incontinence therapy (Figure 4). In addition, hydrogel materials find increasingly growing applications in the construction of educational simulation models of organs and specific conditions of the urinary system, which enable the education of medical personnel. Numerous research efforts are underway to expand the existing treatment methods and reconstruction of the urinary system based on hydrogel materials. After conducting the further necessary research, many of the innovative solutions developed to date have high application potential.
Cerium oxide nanoparticles (CeONPs) displayed cytotoxic properties against some cancer cells. However, there is very limited data about the possible antitumoral potential of them in breast cancer cells when used alone and/or together with a chemotherapeutic drug. We investigated the effects of CeONPs alone or in combination with paclitaxel (PAC) on healthy or carcinoma breast cells. After human breast cancer cells (MCF‐7) treated with CeONPs alone or together with PAC for 24, 48, and 72 h, the effects of CeONPs on cell viability, apoptosis, migration, and adhesion were investigated. All cell viability and IC50 values of CeONPs and PAC treatments in healthy breast cells (HTERT‐HME1) were higher than MCF‐7 cells. They showed higher cytotoxicity against MCF‐7 cells. CeONPs (10, 20, and 30 mM) and/or abraxane (AB) (2 μM) significantly decreased cell viability values in MCF‐7 cells. All CeONPs concentrations increased the number of apoptotic MCF‐7 cells. CeONPs (20 and 30 mM) alone or in combination with AB for 72 h treatment also significantly increased the apoptosis in compared to AB alone. CeONPs and/or AB can significantly inhibit the migratory ability of breast cancer cells. The migration rates in co‐treated groups with CeONPs and AB were lower than CeONPs treatments. Higher concentrations of CeONPs alone or together with AB inhibited cell adhesion. Our results showed CeONPs can increase cytotoxicity and apoptosis and decrease cell migration and cell adhesion when used alone or together with AB. Therefore, combination of chemotherapeutics with CeONPs may provide a good strategy against cancer.
Vascular graft failure has persisted as a major clinical problem. Mechanical, structural, and transport properties of vascular grafts are critical factors that substantially affect their function and thus the outcome of implantation. The manufacturing method, post‐processing technique, and material of choice have a significant impact on these properties. The goal of this work is to use thermal treatment to modulate the transport properties of PCL‐based vascular engineered constructs. To this end, we electrospun PCL tubular constructs and thermally bonded the electrospun fibers in a convective oven at various temperatures (54, 57, and 60°C) and durations of treatment (15, 30, and 45 s). The effects of fiber thermal bonding (thermobonding) on the transport, mechanical, and structural properties of PCL tubular constructs were characterized. Increasing the temperature and treatment duration enhanced the degree of thermobonding by removing the interconnected void and fusing the fibers. Thermobonding at 57°C and 60°C for longer than 30 s increased the median tangential modulus (E = 126.1 MPa, [IQR = 20.7]), mean suture retention (F = 193.8 g, [SD = 18.5]), and degradation rate while it decreased the median permeability (kA = 0 m/s), and median thickness (t = 60 μm, [IQR = 2.5]). In particular, the thermobonding at 57°C allowed a finer modulation of permeability via treatment duration. We believe that the thermobonding method can be utilized to modulate the properties of vascular engineered constructs which can be useful in designing functional vascular grafts.
The temporomandibular joint (TMJ) disc, meniscus and intervertebral disc (IVD) are three fibrocartilage discs, which play critical roles in our daily life. Their degeneration contributes to diseases such as TMJ disorders, osteoarthritis and degenerative disc disease, affecting patients' quality of life and causing substantial morbidity and mortality. Interestingly, similar in some aspects of fundamental characteristics, they exhibit differences in other aspects such as biomechanical properties. Highlighting these similarities and differences can not only benefit a comprehensive understanding of them and their pathology but also assist in future research of tissue engineering. Likewise, comparing their tissue engineering in cell sources, scaffold and stimuli can guide imitation and improvement of their engineered discs. However, the anatomical structure, function, and biomechanical characteristics of the IVD, TMJ, and Meniscus have not been compared in any meaningful depth needed to advance current tissue engineering research on these joints, resulting in incomplete understanding of them and their pathology and ultimately limiting future research of tissue engineering. This review, for the first time, comprehensively compares three fibrocartilage discs in those aspects to cast light on their similarities and differences.
The porcine‐derived non‐cross‐linked collagen membrane Bio‐gide® (BG) and the bovine‐derived non‐cross‐linked collagen membrane Heal‐all® (HA) were compared to better understand their in vitro biophysical characteristics and in vivo degradation patterns as a reference for clinical applications. It was showed that the porosity, specific surface area, pore volume and pore diameter of BG were larger than those of HA (64.5 ± 5.2% vs. 48.6 ± 6.1%; 18.6 ± 2.8 m2/g vs. 2.3 ± 0.6 m2/g; 0.114 ± 0.002 cm3/g vs. 0.003 ± 0.001 cm3/g; 24.4 ± 3.5 nm vs. 7.3 ± 1.7 nm, respectively); the average swelling ratio of BG was higher than that of HA (412.6 ± 41.2% vs. 270.0 ± 2.7%); the tensile strength of both dry and wet HA was higher than those of BG (18.26 ± 3.27 MPa vs. 4.02 ± 1.35 MPa; 2.24 ± 0.21 MPa vs. 0.16 ± 0.02 MPa, respectively); 73% of HA remained after 72 h in collagenase solution, whereas only 8.2% of BG remained. A subcutaneous rat implantation model revealed that, at 3, 7, 14, 28, and 56 days postmembrane implantation, there were more total inflammatory cells, especially more M1 and M2 polarized macrophages and higher M2/M1 ratio in BG than in HA; in addition, the fibrous capsule around BG was also thicker than that around HA. Moreover, concentrations of dozens of cytokines including interleukin‐2(IL‐2), IL‐7, IL‐10 and so forth. in BG were higher than those in HA. It is suggested that BG and HA might be suitable for different clinical applications according to their different characteristics.
Descending and ascending fiber tracts in the spinal cord
(A) schematic view of astrocytes that form the parallel array of processes along the axon in the intact spinal cord. (B) The reactivation of astrocytes after an injury that creates a glial scar
Scaffold design for axon regeneration after spinal cord injury
The healing process for spinal cord injuries is complex and presents many challenges. Current advances in nerve regeneration are based on promising tissue engineering techniques, However, the chances of success depend on better mimicking the extracellular matrix (ECM) of neural tissue and better supporting neurons in a three‐dimensional environment. The ECM provides excellent biological conditions, including desirable morphological features, electrical conductivity, and chemical compositions for neuron attachment, proliferation and function. This review outlines the rationale for developing a construct for neuron regrowth in spinal cord injury using appropriate biomaterials and scaffolding techniques.
System used for the 3D axisymmetric simulation considering a lens of 71 μm central thickness and −3.00 dioptres
Values for oxygen tension under open (A) and closed (B) eye conditions, oxygen flux module for open (C) and closed eye (D), oxygen tension (E) and oxygen flux module (F) over lines crossing the entire system (yellow paths in Figure 1), lines of oxygen flux (G) and time‐dependent transient oxygen tension (H) for a Galyfilcon A lens
Values for oxygen tension under open (A) and closed (B) eye conditions, oxygen flux module for open (C) and closed eye (D), oxygen tension (E) and oxygen flux module (F) over lines crossing the entire system (yellow paths in Figure 1), lines of oxygen flux (G) and time‐dependent transient oxygen tension (H) for a Balafilcon A lens
Values for oxygen tension under open (A) and closed (B) eye conditions, oxygen flux module for open (C) and closed eye (D), oxygen tension (E) and oxygen flux module (F) over lines crossing the entire system (yellow paths in Figure 1), lines of oxygen flux (G) and time‐dependent transient oxygen tension (H) for a Lotrafilcon A lens
We perform a novel 3D study to quantify the corneal oxygen consumption and diffusion in each part of the cornea with different contact lens materials. The oxygen profile is calculated as a function of oxygen tension at the cornea‐tear interface and the oxygen transmissibility of the lens, with values used in previous studies. We aim to determine the influence of a detailed geometry of the cornea in their modeling compared to previous low dimensional models used in the literature. To this end, a 3‐D study based on an axisymmetric volume element analysis model was applied to different contact lenses currently on the market. We have obtained that the model provides a valuable tool for understanding the flux and cornea oxygen profiles through the epithelium, stroma, and endothelium. The most important results are related to the dependence of the oxygen flux through the cornea‐lens system on the contact lens thickness and geometry. Both parameters play an important role in the corneal flux and oxygen tension distribution. The decline in oxygen consumption experienced by the cornea takes place just inside the epithelium, where the oxygen tension falls to between 95 and 16 mmHg under open eye conditions, and 30 to 0.3 mmHg under closed eye conditions, depending on the contact lens worn. This helps to understand the physiological response of the corneal tissue under conditions of daily and overnight contact lens wear, and the importance of detailed geometry of the cornea in the modeling of diffusion for oxygen and other species. A full 3D axisymmetric and time‐dependent model of the cornea‐lens system has been numerically solved to determine the oxygen flux and consumption in each part of the cornea. We apply our model to different lenses currently usted on the market, showing the importance of detailed geometry in the modelling of these systems.
The lumbar intervertebral devices are widely used in the surgical treatment of lumbar diseases. The subsidence represents a serious clinical issue during the healing process, mainly when the interfaces between the implant and the vertebral bodies are not well designed. The aim of this study is the evaluation of subsidence risk for two different devices. The devices have the same shape, but one of them includes a filling micro lattice structure. The effect of the micro lattice structure on the subsidence behavior of the implant was evaluated by means of both experimental tests and finite element analyses. Compressive tests were carried out by using blocks made of grade 15 polyurethane, which simulate the vertebral bone. Non‐linear, quasi‐static finite element analyses were performed to simulate experimental and physiologic conditions. The experimental tests and the FE analyses showed that the subsidence risk is higher for the device without micro lattice structure, due to the smaller contact surface. Moreover, an overload in the central zone of the contact surface was detected in the same device and it could cause the implant failure. Thus, the micro lattice structure allows a homogenous pressure distribution at the implant–bone interface.
Magnesium (Mg) alloy‐based porous bio‐nanocomposite bone scaffolds were developed by powder metallurgy route. Selective alloying elements such as calcium (Ca), zinc (Zn) and strontium (Sr) were incorporated to tune the mechanical integrity while, bioactive fluorcanasite nano‐particulates were introduced within the alloy system to enhance the bone tissue regeneration. Green compacts containing carbamide were fabricated and sintered using two‐stage heat treatment process to achieve the targeted porosities. The microstructure of these fabricated magnesium alloy‐based bio‐nanocomposites was examined by Field emission scanning electron microscope (FE‐SEM) and x‐ray micro computed tomography (x‐ray μCT), which revealed gradient porosities and distribution of alloying elements. X‐ray diffraction (XRD) studies confirmed the presence of major crystalline phases in the fabricated samples and the evolution of the various combinations of intermetallic phases of Ca, Mg, Zn and Sr which were anticipated to enhance the mechanical properties. Further, XRD studies revealed the presence of apatite phase for the immersed samples, a conducive environment for bone regeneration. The fabricated samples were evaluated for their mechanical performance against uniaxial compression load. The tunability of compressive strengths and modulus values could be established with variation in porosities of fabricated samples. The retained compressive strength and Young's modulus of the samples following immersion in phosphate buffered saline (PBS) solution was found to be in line with that of natural human cancellous bone, thereby establishing the potential of the fabricated magnesium‐alloy‐based nanocomposite as a promising scaffold candidate for bone tissue engineering.
Acellular vascular scaffolds with capture molecules have shown great promise in recruiting circulating endothelial colony forming cells (ECFCs) to promote in vivo endothelialization. A microenvironment conducive to cell spreading and differentiation following initial cell capture are key to the eventual formation of a functional endothelium. In this study, syndecan‐4 and stromal cell‐derived factor‐1 alpha were used to functionalize an elastomeric biomaterial composed of poly(glycerol sebacate), Silk Fibroin and Type I Collagen, termed PFC, to enhance ECFC‐material interaction. Functionalized PFC (fPFC) showed significantly greater ECFCs capture capability under physiological flow. Individual cell spreading area on fPFC (1474 ± 63 μm2) was significantly greater than on PFC (1187 ± 54 μm2) as early as 2 h, indicating enhanced cell–material interaction. Moreover, fPFC significantly upregulated the expression of endothelial cell specific markers such as platelet endothelial cell adhesion molecule (24‐fold) and Von Willebrand Factor (11‐fold) compared with tissue culture plastic after 7 days, demonstrating differentiation of ECFCs into endothelial cells. fPFC fabricated as small diameter conduits and tested using a pulsatile blood flow bioreactor were stable and maintained function. The findings suggest that the new surface functionalization strategy proposed here results in an endovascular material with enhanced endothelialization.
The composition of carbonate apatite (CO3Ap) aids bone regeneration. Other features, such as porosity and pore interconnectivity of artificial bone, also govern bone regeneration. In general, a trade‐off exists between the porosity and mechanical strength of artificial bone. Therefore, this suggests that the interconnected pores in the ant‐nest‐type porous (ANP) structure of artificial bone accelerate bone regeneration by minimizing the sacrifice of mechanical strength. The unique structure of polyurethane foam has the potential to endow CO3Ap with an ANP structure without forming excess pores. This study investigated the efficacy of polyurethane foam as a porogen in providing ANP structure to CO3Ap artificial bone. The polyurethane foam was completely decomposed by sintering and the resulting CO3Ap displayed ANP structure with a compressive strength of approximately 15 MPa. Furthermore, in vivo experiments revealed that the migration of cells and tissues into the interior of CO3Ap through the interconnected pores accelerated bone regeneration in the ANP‐structured CO3Ap. Thus, this indicates that using polyurethane foam as a porogen endows the CO3Ap artificial bone with an ANP structure that accelerates bone regeneration.
We previously showed decellularized fish swim bladder can be used as vascular patch and tube graft in rats, mesenchymal stem cells (MSCs) have showed the capability to inhibit neointimal hyperplasia in different animal models. We hypothesized that decellularized fish swim bladder patch loaded with MSCs (bioinspired patch) can inhibit neointimal hyperplasia in a rat aortic patch angioplasty model. Rat MSCs were grown in vitro and flow cytometry was used to confirm their quality. 3.6 × 105 MSCs were mixed into 100 μl of sodium alginate (SA)/hyaluronic acid (HA) hydrogel, two layers of fish swim bladders (5 mm × 5 mm) were sutured together, bioinspired patch was created by injection of hydrogel with MSCs into the space between two layers of fish swim bladder patches. Decellularized rat thoracic aorta patch was used as control. Patches were harvested at days 1 and 14 after implantation. Samples were examined by histology, immunohistochemistry, and immunofluorescence. The decellularized rat thoracic aorta patch and the fish swim bladder patch had a similar healing process after implantation. The bioinspired patch had a similar structure like native aorta. Bioinspired patch showed a decreased neointimal thickness (p = .0053), fewer macrophages infiltration (p = .0090), and lower proliferation rate (p = .0291) compared to the double layers fish swim bladder patch group. Decellularized fish swim bladder patch loaded with MSCs can inhibit neointimal hyperplasia effectively. Although this is a preliminary animal study, it may have a potential application in large animals or clinical research.
Periodontitis is a chronic inflammatory disease that leads to the loss of alveolar bone, among several studies focusing on reconstructing periodontal bone caused by periodontitis, guided bone regeneration (GBR) is a promising approach. In this study a serial clinically applied antibiotics loaded poly(L‐lactide‐co‐glycolide)/poly(L‐lactide‐co‐ε‐caprolactone) (PLGA/PLCA) fibrous mesh to prevent and reconstruct defective bone in periodontitis were prepared by electrospinning. Incorporation of antibiotics promoted the hydrophilicity but decreased the crystallinity of PLGA/PLCA membranes. Antibiotics could be sustained released from membranes. Metronidazole, minocycline, and doxycycline incorporated membranes could suppress Porphyromonas gingivalis (P. gingivalis) within 21 days in vitro. Metronidazole and minocycline incorporated membranes decreased 41% and 55.5% colony counts in rat gingival crevicular fluid in vivo. Minocycline‐loaded membrane could support the proliferation of MC3T3‐E1 cells and maintained 79% viability of human ligament fibroblasts cultured on it. And MC3T3‐E1 cells could undergo osteoblastic differentiation when cultured with pure PLGA/PLCA membrane and minocycline incorporated membrane. Then in vivo repairable effects of those antibiotics loaded membranes were evaluated in alveolar bone defected P. gingivalis infected model. The application of minocycline loaded membranes, effectively prevented the bone resorption of periodontitis caused by P. gingivalis. After been treated with minocycline incorporated membrane, volume of defected bone of maintained at about 50% level of control rats. 8 weeks post‐operation, newly regenerated bone was observed in the operative alveolar bone of the pure PLGA/PLCA membrane, metronidazole and minocycline incorporated PLGA/PLCA membrane treated groups. Minocycline/PLGA/PLCA electrospinning membrane is a promising GBR material that can be applied to guide regeneration of periodontitis‐induced alveolar bone damage.
Two‐dimensional cross‐sectional images (A) and 3D reconstruction images (B) of implants and the surrounding bones by micro‐CT. (C) Quantitative analyses of new bone around implants by micro‐CT. *p < .05, **p < .01, and ***p < .001, when compared with 30%‐carbon fiber reinforced polyetheretherketone; #p < .05, ##p < .01, and ### p < .001, when the control group is Ti
(A) Scanning electronic microscope (SEM) images of the implant‐bone interfaces. (B) SEM and energy dispersive x‐ray images represented bone deposited and elemental maps on the implant surface
(A) Confocal laser scanning microscope images of new bone with fluorochrome sequential labeling. (B) Comparison of mineral apposition ratio among 30%‐carbon fiber reinforced polyetheretherketone (CPEEK), A‐30%‐CPEEK and Ti. *p < .05, **p < .01, and ***p < .001, when 30%‐CPEEK was control
Histological analysis of implant‐bone interface 5 weeks after implantation. (A) Histological reconstruction of the implant and surrounding bone area. (B) Magnify images of the region in (A), in which the white and black arrows indicated fibrous connective tissue and direct bone contact, respectively. (C) Determination of the region of interest for BIC. (D) Percentage of BIC in 30%‐carbon fiber reinforced polyetheretherketone (CPEEK), A‐30%‐CPEEK and Ti. *p < .05 and **p < .01, when compared with 30%‐CPEEK
Polyetheretherketone (PEEK) has become increasingly popular in dentistry and orthopedics due to its excellent chemical stability, reliable biosafety, and low elastic modulus. However, PEEK's biomechanical strength and bioactivity are limited and need to be increased as an implant material. The previous study in vitro has shown that the amino‐functionalized carbon fiber reinforced PEEK (A‐30%‐CPEEK) possessed enhanced mechanical property and bioactivity. This study aims to evaluate the effect of amino groups modification on the osseointegration behavior of carbon fiber reinforced PEEK (30%‐CPEEK) in rabbits. Herein, 30%‐CPEEK and A‐30%‐CPEEK implant discs were implanted in rabbit skulls for 5 weeks, with pure titanium implants serving as a control. The bone‐forming ability and osseointegration in vivo were systematically investigated by micro‐computed tomography analysis, scanning electron microscope observation, and histological evaluation. Our results showed that all detection parameters were significantly different between the A‐30%‐CPEEK and 30%‐CPEEK groups, favoring those in the A‐30%‐CPEEK, whose appraisal parameters were equal to or better than pure titanium. Therefore, this study supported the importance of amino groups in facilitating the new bone formation and bone‐implant integration, suggesting that A‐30%‐CPEEK with enhanced osseointegration will be a promising material for dental or orthopedic implants.
Polyvinylidene fluoride (PVDF) has been considered as an alternative suture material to replace polypropylene (PP) due to its superior biocompatibility and mechanical properties, but it has never been examined for use in barbed sutures, particularly for tendon repair. This study fabricated size 2–0 PVDF and PP bidirectional barbed sutures and compared their mechanical properties and anchoring performance in patellar tendons. The mechanical properties were evaluated via tensile testing, and the anchoring performance of the barbed sutures was assessed by a tendon suture pullout test. Sixty porcine patellar tendons were harvested, transected to mimic a full‐thickness injury, and repaired using a cross‐locked cruciate suturing technique. The ultimate tensile force was 60% higher for the PVDF barbed sutures (22.4 ± 2.1 N) than for the PP barbed sutures (14.0 ± 1.7 N). The maximum pullout force was 35% higher for PVDF barbed sutures (70.8 ± 7.8 N) than for PP barbed sutures (52.4 ± 5.8 N). The force needed to form a 2‐mm gap, indicative of repair failure, was similar between the PVDF (29.2 ± 5.0 N) and PP (25.6 ± 3.1 N) barbed sutures, but both were greater than the 2‐mm‐gap forces for non‐barbed sutures of the same size. In this study, PVDF barbed sutures provided better mechanical properties and improved tissue anchoring performance compared to the barbed PP sutures for porcine patellar tendon repair, demonstrating that PVDF monofilament sutures can be barbed and used effectively for tendon repair.
Flanged acetabular cups were developed with the rationale that, at insertion, they would increase the pressure of the cement and improve penetration of cement into the acetabular bone. Various studies have been inconclusive regarding their effectiveness. In this work, we aimed to eliminate all confounding factors and measure the pressures generated during acetabular pressurization and cup implantation using a simplified steel acetabulum, high precision pressure transducers, proper surgical techniques and two acetabular cups, identical apart from the addition of a flange to one. It was found that the flanged acetabular component did not significantly increase the pressure in the acetabulum and in some cases reduced the pressures generated when compared to an unflanged cup. The addition of a flange did not reduce the pressure differential between the pole and the rim of the acetabulum, nor did it have a significant effect on pressure lost over the cup implantation period. It was concluded that flanged acetabular cups provide no significant improvement in the pressures generated in the acetabulum during acetabular cup implantation. It is hypothesized that the flange may be seen as a design feature intended to slow the insertion of the cup into the cement, thus requiring the surgeon to apply a larger load in order to correctly position the acetabular cup; in this way larger pressure will be generated.
As the biocompatibility and bioactive potential of repair materials are desired characteristics in dentistry, the tissue response of Bio‐C Pulpo, a bioceramic material launched on the marked by Angelus (Brazil), was compared with Biodentine (Septodont, France) and White MTA (WMTA; Angelus, Brazil). In 32 rats, 148 polyethylene tubes filled with Bio‐C Pulpo, Biodentine or WMTA, and empty (CG, control group) were implanted into subcutaneous tissues for 7, 15, 30, and 60 days. The capsule thickness, numerical density of inflammatory cells (IC) and fibroblasts (Fb), amount of collagen, immunohistochemistry detection of interleukin‐6 (IL‐6) and osteocalcin (OCN), von Kossa and analysis under polarized light were performed. Data were subjected to two‐way ANOVA followed by Tukey's test (p ≤ 0.05). At 7 and 15 days, the capsules around Bio‐C Pulpo were thicker than in WMTA while, at 30 and 60 days, significant differences were not observed among the groups. Although at 7, 15, and 30 days, a greater number of IL‐6‐immunostained cells was found in Bio‐C Pulpo and Biodentine than in WMTA, no significant difference was detected among the groups at 60 days. In all groups, the number of Fb and collagen content increased significantly over time. The capsules around materials exhibited von Kossa‐positive and birefringent structures, and OCN‐immunostained cells whereas, in the CG, these structures were not observed. Bio‐C Pulpo, similarly to Biodentine and WMTA, is biocompatible, allows the connective tissue repair and presents bioactive potential in connective tissue of rats.
This study aimed to understand the effect of physiological and dental implant‐related parameter variations on the osseointegration for an implant‐supported fixed prosthesis. Eight design factors were considered (implant shape, diameter, and length; thread pitch, depth, and profile; cantilever [CL] length and implant‐loading protocol). Total 36 implantation scenarios were simulated using finite element method based on Taguchi L36 orthogonal array. Three patient‐specific bone conditions were also simulated by scaling the density and Young's modulus of a mandible sample to mimic weak, normal, and strong bones. Taguchi method was employed to determine the significance of each design factor in controlling the peri‐implant cortical bone microstrain. For normal bone condition, CL length had the maximum contribution (28%) followed by implant diameter (18%), thread pitch (14%), implant length (8%), and thread profile (5%). For strong bone condition, CL and implant diameter had equal contribution (32%) followed by thread pitch (7%) and implant length (5%). For weak bone condition, implant diameter had the highest contribution (31%) followed by CL length (30%), thread pitch (11%) and implant length (8%). The presence of distal CL in dental framework was found to be the most influential design factor, which can cause high strain in the cervical cortical bone. It was seen that implant diameter had more effect compared to implant length toward peri‐implant bone biomechanical response. Implant‐loading time had no significant effect towards peri‐implant bone biomechanical response, signifying immediate loading is possible with sufficient mechanical retention.
In this study, graphene oxide (GO) was functionalized with polyethylene glycol (PEG) to understand the effect of PEGlayted GO on properties of chitosan‐based nanocomposite scaffold. GO was synthesized according to modified Hummer's method and covalently linked to polymeric chains of PEG to produce polyethylene glycolated GO (PGO). Successful preparation of GO and PGO was confirmed by FT‐IR and Raman techniques, where the chemical bonding of PEG and GO nanosheets were concluded based on PGOs' lower zeta potential compared to GO. Nanocomposite scaffolds were prepared by adding equal amounts of GO and PGO into 2% (w/v) chitosan (Cs) solutions. The highly porous scaffolds were developed by lyophilization of solutions. Incorporation of GO and PGO into chitosan scaffold network resulted in uniform and spherical pores. Modified samples offered higher porosity and density, indicating adequate scaffold structure. Improvements in the physical properties of prepared chitosan scaffolds were concluded through higher water absorption and retention values. Compressive strength measurement showed 6.33 and 5.5 times improvement respectively for Cs‐GO and Cs‐PGO samples compared to Cs scaffold. The Cs‐GO scaffolds showed minimum susceptibility toward enzymatic degradation and higher degrees of protein adsorption (26% and 23% improvement in value of adsorbed protein respectively for Cs‐GO and Cs‐PGO compared to Cs scaffold) and biomineral formation on scaffold surface. Also, Cs‐PGO sample showed the highest degree of cell viability and lower hemolysis than both Cs and Cs‐GO scaffolds. Investigations showed that cell infiltration into scaffold porous structure was more prominent in Cs‐PGO scaffolds than in Cs and Cs‐GO scaffolds.
Stereolithographic bioprinting holds great promise in the quest for creating artificial, biomimetic cartilage‐like tissue. To introduce a more biomimetic approach, we examined blending and stratifying methacrylated hyaluronic acid (HAMA) and methacrylated gelatin (GelMA) bioinks to mimic the zonal structure of articular cartilage. Bioinks were suspended with porcine chondrocytes before being printed in a digital light processing approach. Homogenous constructs made from hybrid bioinks of varying polymer ratios as well as stratified constructs combining different bioink blends were cultivated over 14 days and analyzed by histochemical staining for proteoglycans/collagen type II, cartilage marker expression analysis, and for cellular viability. The stiffness of blended bioinks increased gradually with HAMA content, from 2.41 ± 0.58 kPa (5% GelMA, 0% HAMA) to 8.84 ± 0.11 kPa (0% GelMA, 2% HAMA). Cell‐laden constructs maintained vital chondrocytes and supported the formation of proteoglycans and collagen type II. Higher concentrations of GelMA resulted in increased formation of cartilaginous matrix proteins and a more premature phenotype. However, decreased matrix production in central areas of constructs was observed in higher GelMA content constructs. Biomimetically stratified constructs retained their gradient‐like structure even after ECM formation, and exclusively exhibited a significant increase in COL2A1 gene expression (+178%). Concluding, we showed the feasibility of blending and stratifying photopolymerizable, natural biopolymers by SLA bioprinting to modulate chondrocyte attributes and to create zonally segmented ECM structures, contributing to improved modeling of cartilaginous tissue for regenerative therapies or in vitro models.
Variation in tissue source, species, and isolation technique has a significant impact on the physical properties of collagen type I (A) Gelation kinetics, (B) polymerization rate determined by linear regression,(C) swelling ratio, (D) in‐vitro collagenase degradation with time, (E) representative stress‐strain curves, and (F) compressive modulus of different collagen type I hydrogels. (* indicates p < .05, ** indicates p < .01, *** indicates p < .001, **** indicates p < .0001).
SEM imaging of hydrogels shows differences in collagen fiber morphology due to variation in tissue source, species, and extraction methods. LIVE/DEAD imaging indicates that hMSCs remain viable over time on collagen type I hydrogels. AlamarBlue assay revealed enhanced cell metabolic activity on rat tail and human skin derived collagen type I hydrogels. (A) SEM and Live/Dead assay to assess cell viability. Scale bar: 5 μm ‐ SEM images; 200 μm ‐ Live/Dead staining images. (B) Quantification of cell viability. (C) Quantification of cell number per surface area. (D) Quantification of cell metabolic activity on collagen type I hydrogels using alamarBlue assay–(* indicates p < .05 when comparing with bovine collagen at the same time point, # indicates p < .05 when comparing with human fibroblasts collagen at the same time point, & indicates p < .05 when comparing with human placenta collagen at the same time point).
ATP quantification demonstrates that matrix‐supported colorectal 3D tumor constructs largely respond in a dose dependent manner to chemotherapy agents Regorafenib and 5‐fluorouracil. ATP luminescence readings of colorectal cancer Caco‐2 3D constructs on days 1, 4, and 7 following drug administration at concentrations of 1, 10, and 100 μm (n=4). Conditions include Regorafenib‐ (Top) and 5‐ fluorouracil‐ (Bottom) treated rat tail collagen type I and human skin collagen type I 3D tumor constructs. Statistical significance: †, * and # ‐ p < .05 between different drug concentrations at a given timepoint; ‡ ‐ p < .05 between timepoints at a given concentration.
LIVE/DEAD visualization of colorectal cancer 3D constructs qualitatively corroborates quantitative data indicating that 3D tumor constructs largely respond in a dose dependent manner to chemotherapy agents. Fluorescent microscope images of colorectal cancer Caco‐2 3D constructs stained with calcein AM (green) and ethidium homodimer‐1 (red) at days 1, 4, and 7 following drug administration at concentrations of 1, 10, and 100 μm (n = 3). Conditions include Regorafenib‐ (Top) and 5‐fluorouracil‐ (Bottom) treated rat tail collagen type I and human skin collagen type I 3D tumor constructs. Green–viable cells stained with calcein AM; Red–dead cells stained with ethidium homodimer‐1. Scale bar: 100 μm.
Effects of rat tail collagen type I and human skin‐derived collagen type I containing hydrogels on human vessel formation in vivo. (A) Photographs of hydrogels prior and 14 days post‐implantation into the abdominal wall of a SCID/bg mouse model. Scale bar: 5 mm. (B) Assessment of gel contraction by measurements of hydrogel weight at the time of implantation and after explant. Data are shown with standard error of mean (SEM) (n = 3; p < .05). (C) Representative H&E images of hydrogels 14 days post‐implantation, showing that rat tail and human skin‐derived collagen type I containing hydrogels support vessel formation in vivo. Immunohistochemical analysis of F4/80 expression shows different degrees of infiltration of murine macrophages. Inset images represent low magnification views of hydrogel crosssections. Scale bar: 500 μm. (D) Quantification of area of F4/80+ staining shows that degree of infiltration is particularly higher in hydrogels containing human skin‐derived collagen type I (* indicates p < .05). (E) Hydrogels formulated with rat tail and human‐skin derived collagen type I contain vascular structures 14 days post‐implantation. Presence of mouse microvessels and basement membrane deposition was assessed by staining with mouse CD31 and human collagen IV antibodies, respectively. To demonstrate that human EC‐lined vessels were perfused, fluorescein ulex was injected 30 min before explant. Staining shows that several human vessels have anastomosed with mouse vessels and became perfused in vivo in rat tail and human skin‐derived collagen type I hydrogels. Post‐harvest staining with rhodamine ulex shows a significant higher number of human EC‐lined vessels in the center of these hydrogels that were not perfused at the time of fluorescein ulex infusion. Scale bar: 500 μm (high magnification images: 100 μm). (F) Quantification of area of infused ulex shows no significant difference in the number of perfused human EClined vessels between conditions. (ns indicates p > .05).
Xenogeneic sources of collagen type I remain a common choice for regenerative medicine applications due to ease of availability. Human and animal sources have some similarities, but small variations in amino acid composition can influence the physical properties of collagen, cellular response, and tissue remodeling. The goal of this work is to compare human collagen type I‐based hydrogels versus animal‐derived collagen type I‐based hydrogels, generated from commercially available products, for their physico‐chemical properties and for tissue engineering and regenerative medicine applications. Specifically, we evaluated whether the native human skin type I collagen could be used in the three most common research applications of this protein: as a substrate for attachment and proliferation of conventional 2D cell culture; as a source of matrix for a 3D cell culture; and as a source of matrix for tissue engineering. Results showed that species and tissue specific variations of collagen sources significantly impact the physical, chemical, and biological properties of collagen hydrogels including gelation kinetics, swelling ratio, collagen fiber morphology, compressive modulus, stability, and metabolic activity of hMSCs. Tumor constructs formulated with human skin collagen showed a differential response to chemotherapy agents compared to rat tail collagen. Human skin collagen performed comparably to rat tail collagen and enabled assembly of perfused human vessels in vivo. Despite differences in collagen manufacturing methods and supplied forms, the results suggest that commercially available human collagen can be used in lieu of xenogeneic sources to create functional scaffolds, but not all sources of human collagen behave similarly. These factors must be considered in the development of 3D tissues for drug screening and regenerative medicine applications.
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3.405 (2021)
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Top-cited authors
A.U. Daniels
  • University of Basel
George J Dias
  • University of Otago
Paulo Coelho
  • New York University College of Dentistry; New York University Langone Medical Center
Kirk P. Andriano
  • BBS Bioactive Bone Substitutes
Zvi Schwartz
  • Virginia Commonwealth University