Biomedical Materials Research Research Articles

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

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

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

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

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

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

Differences in biocompatibility of microneedles from cyclic olefin polymers with human endothelial and epithelial skin cells

Microneedles are promising devices for transdermal delivery and diagnostic applications, due to their minimally invasive and painless nature of application. However, so far, applications are limited to small scale research projects. Material selection and production for larger projects remain a challenge. In vitro testing using human cell culture could bridge the gap between cost effective screening of suitable materials and concerns for safety and ethics. In this study, materials were tested for effects on viability and morphology of human endothelial cells and keratinocytes. In addition, materials were assessed for their potential to influence cellular differentiation and barrier formation. Elution‐based testing of inflammatory markers revealed no negative effects in all applied tests, whereas the assessment of differentiation markers on cells in direct contact with the material showed differences and allowed the selection of candidate materials for future medical device applications. This study illustrates that elution‐based biocompatibility testing can paint an incomplete picture. Advanced staining techniques and cell types specific for the application of the medical device improve material selection to reduce and replace animal testing at an early stage in the development process. © 2018 The Authors. journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 505–512, 2019.

Tuning of hydrogel stiffness using a two-component peptide system for mammalian cell culture.

Self‐assembling peptide hydrogels (SAPHs) represent emerging cell cultures systems in several biomedical applications. The advantages of SAPHs are mainly ascribed to the absence of toxic chemical cross‐linkers, the presence of ECM‐like fibrillar structures and the possibility to produce hydrogels with a large range of different mechanical properties. We will present a two‐component peptide system with tuneable mechanical properties, consisting of a small pentapeptide (SFFSF‐NH2, SA5N) that acts as a gelator and a larger 21‐mer peptide (SFFSF‐GVPGVGVPGVG‐SFFSF, SA21) designed as a physical cross‐linker. The hydrogels formed by different mixtures of the two peptides are made up mainly of antiparallel β‐sheet nanofibers entangling in an intricate network. The effect of the addition of SA21 on the morphology of the hydrogels was investigated by atomic force microscopy and transmission electron microscopy and correlated to the mechanical properties of the hydrogel. Finally, the biocompatibility of the hydrogels using 2D cell cultures was tested. © 2018 The Authors. journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 535–544, 2019.

Biocompatibility of common implantable sensor materials in a tumor xenograft model.

Real‐time monitoring of tumor microenvironment parameters using an implanted biosensor could provide valuable information on the dynamic nature of a tumor's biology and its response to treatment. However, following implantation biosensors may lose functionality due to biofouling caused by the foreign body response (FBR). This study developed a novel tumor xenograft model to evaluate the potential of six biomaterials (silicon dioxide, silicon nitride, Parylene‐C, Nafion, biocompatible EPOTEK epoxy resin, and platinum) to trigger a FBR when implanted into a solid tumor. Biomaterials were chosen based on their use in the construction of a novel biosensor, designed to measure spatial and temporal changes in intra‐tumoral O2, and pH. None of the biomaterials had any detrimental effect on tumor growth or body weight of the murine host. Immunohistochemistry showed no significant changes in tumor necrosis, hypoxic cell number, proliferation, apoptosis, immune cell infiltration, or collagen deposition. The absence of biofouling supports the use of these materials in biosensors; future investigations in preclinical cancer models are required, with a view to eventual applications in humans. To our knowledge this is the first documented investigation of the effects of modern biomaterials, used in the production of implantable sensors, on tumor tissue after implantation. © 2018 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1620–1633, 2019.

Antibiotics release from cement spacers used for two-stage treatment of implant-associated infections after total joint arthroplasty.

Two‐stage revision arthroplasty is the treatment of choice for periprosthetic infection, a serious complication after knee or hip arthroplasty. Our prospective clinical trial aimed to investigate the concentrations of gentamicin and vancomycin in wound exudate and tissue in two‐stage revision arthroplasty. Wound exudate and periprosthetic membrane samples were collected from 18 patients (10 hip and eight knee patients), who were due for two‐stage treatment after a periprosthetic joint infection. Samples were taken during insertion of antibiotic‐impregnated spacers and after their removal. The concentrations of gentamicin and vancomycin in wound exudates and adjacent tissue were analyzed using high‐performance liquid chromatography mass spectrometry. Average time period of spacer implantation was 13.6 weeks (9.3–22.6 weeks). The concentration of vancomycin in wound exudate decreased from a median of 43.28 μg/mL (0.28–261.22) after implantation to 0.46 μg/mL (0.13–37.47) after the removal of the spacer. In the adjacent tissue, vancomycin concentration was mainly undetectable prior to spacer implantation (0.003 μg/g [0.003–0.261]) and increased to 0.318 μg/g [0.024–484.16] at the time of spacer removal. This was also observed for gentamicin in the tissue of patients who previously had cement‐free implants (0.008 μg/g [0.008–0.087] vs. 0.164 μg/g [0.048–71.75]) while in the tissue of patients with previously cemented prosthesis, baseline concentration was already high (8.451 μg/g [0.152–42.926]). Despite the rapid decrease in antibiotics release from spacer cement observed in vitro, in vivo antibiotics are much longer detectable, especially in the adjacent soft tissue. © 2018 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials Published By Wiley Periodicals, Inc. J Biomed Mater Res B Part B, 2019. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1587–1597, 2019.

High modulus hydrogels for ophthalmic and related biomedical applications.

This paper presents three families of semi-interpenetrating polymer network (SIPN) hydrogels based on an ester-based polyurethane (EBPU) and hydrophilic monomers: N,N-dimethylacrylamide (NNDMA), N-vinyl pyrrolidone (NVP) and acryloylmorpholine (AMO) as potential materials for keratoprosthesis, orthokeratology and mini-scleral lens application. Hydrogels sheets were synthesized via free-radical polymerization with methods developed in-house. SIPN hydrogels were characterized for their equilibrium water content, mechanical and surface properties. Three families of optically clear SIPN-based hydrogels have been synthesized in the presence of water with >10% of composition attributable to EBPU. Water contents of SIPN materials ranged from 30% to 70%. SIPNs with ≤15% EBPU of total composition showed little influence to mechanical properties, whereas >15% EBPU contributed significantly to an increase in material stiffness. In the hydrated state, SIPNs with ≤15% EBPU of total composition show little difference in polar component (γp ) of surface free energy, whereas for >15% EBPU there is a decrease in γp . The EBPU SIPN hydrogels display complementary material properties for keratoprosthesis, orthokeratology, and mini-scleral applications. © 2018 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1645-1653, 2019.

An on-site preparable, novel bone-grafting complex consisting of human platelet-rich fibrin and porous particles made of a recombinant collagen-like protein.

Platelet‐rich fibrin (PRF) is widely used in regenerative medicine. Nonetheless, major issues include its controversial effects on bone regeneration and a lack of quality‐assured glass tubes required for coagulation. We used porous particles (FBG) comprising a recombinant RGD motif‐enriched collagen I‐like protein to activate the coagulation pathway and examined the effects of the resulting PRF–FBG complex on bone regeneration. Human whole‐blood samples were mixed with FBG in plastic tubes and centrifuged to prepare a PRF–FBG complex. Platelet‐derived growth factor‐BB (PDGF‐BB) levels and cell growth activity were determined by ELISA and a bioassay using osteoblasts. Bone regenerative activity was assessed using a mouse model of calvarial bone defect. FBG facilitated PRF‐like matrix formation during centrifugation. In this PRF–FBG complex, the microstructure of fibrin fibers was similar to that of PRF prepared conventionally in glass tubes. PDGF‐BB levels and mitogenic action were not significantly influenced by FBG. In the bone defect model, although PRF did not exert any significant positive effects on its own, in combination with FBG, it synergistically stimulated new bone formation. This study demonstrated that incorporation of FBG into whole‐blood samples induces PRF formation without the aid of glass tubes. The resulting PRF–FBG complex could be a promising bone grafting material in clinical settings. © 2018 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1420–1430, 2019.

Tyramine-conjugated alginate hydrogels as a platform for bioactive scaffolds.

Alginate‐based hydrogels represent promising microenvironments for cell culture and tissue engineering, as their mechanical and porous characteristics are adjustable toward in vivo conditions. However, alginate scaffolds are bioinert and thus inhibit cellular interactions. To overcome this disadvantage, bioactive alginate surfaces were produced by conjugating tyramine molecules to high‐molecular‐weight alginates using the carbodiimide chemistry. Structural elucidation using nuclear magnetic resonance spectroscopy and contact angle measurements revealed a surface chemistry and wettability of tyramine‐alginate hydrogels similar to standard cell culture treated polystyrene. In contrast to stiff cell culture plastic, tyramine‐alginate scaffolds were found to be soft (60–80 kPa), meeting the elastic moduli of human tissues such as liver and heart. We further demonstrated an enhanced protein adsorption with increasing tyramine conjugation, stable for several weeks. Cell culture studies with human mesenchymal stem cells and human pluripotent stem cell‐derived cardiomyocytes qualified tyramine‐alginate hydrogels as bioactive platforms enabling cell adhesion and contraction on (structured) 2‐D layer and spherical matrices. Due to the alginate functionalization with tyramines, stable cell–matrix interactions were observed beneficial for an implementation in biology, biotechnology, and medicine toward efficient cell culture and tissue substitutes. © 2018 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 114–121, 2019.

Thrombogenicity assessment of Pipeline Flex, Pipeline Shield, and FRED flow diverters in an in vitro human blood physiological flow loop model.

Endovascular treatment of intracranial aneurysms with endoluminal flow diverters (single or multiple) has proven to be clinically safe and effective, but is associated with a risk of thromboembolic complications. Recently, a novel biomimetic surface modification with covalently bound phosphorylcholine (Shield Technology™) has shown to reduce the material thrombogenicity of the Pipeline flow diverter. Thrombogenicity of Pipeline Flex, Pipeline Shield, and Flow Redirection Endoluminal Device (FRED) in the presence of human blood under physiological flow conditions—in addition to relative increase in thrombogenicity with multiple devices—remains unknown and was investigated here. Thrombin generation (mean ± SD; μg/mL; thrombin–antithrombin complex or TAT) was measured as FRED (30.3 ± 2.9), Pipeline (13.9 ± 4.4), Pipeline Shield (0.4 ± 0.3), and negative control (no device; 0.1 ± 0.0). Platelet activation (mean ± SD; IU/μL; beta‐thromboglobulin or βTG) was measured as FRED (148 ± 45), Pipeline (92.8 ± 41), Pipeline Shield (16.2 ± 3.5), and negative control (2.70 ± 0.16). FRED was significantly more thrombogenic than Pipeline and Pipeline Shield (p < 0.05) for TAT. Additionally, Pipeline Shield had significantly lower TAT and βTG than the other devices tested (p < 0.05) and these were comparable to the negative control (p > 0.05). TAT and βTG scaled proportionately with multiple Pipeline devices (N = 6) but was unaffected by multiple Pipeline Shield (N = 6) devices—the latter being statistically similar to negative control (p > 0.05). © 2018 The Authors. Journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3195–3202, 2018.

A 3D in vitro model of the dermoepidermal junction amenable to mechanical testing.

Recessive dystrophic Epidermolysis Bullosa (RDEB) is caused by mutations in collagen‐type VII gene critical for the dermoepidermal junction (DEJ) formation. Neither tissues of animal models nor currently available in vitro models are amenable to the quantitative assessment of mechanical adhesion between dermal and epidermal layers. Here, we created a 3D in vitro DEJ model using extracellular matrix (ECM) proteins of the DEJ anchored to a poly(ethylene glycol)‐based slab (termed ECM composites) and seeded with human keratinocytes and dermal fibroblasts. Keratinocytes and fibroblasts of healthy individuals were well maintained in the ECM composite and showed the expression of collagen type VII over a 2‐week period. The ECM composites with healthy keratinocytes and fibroblasts exhibited yield stress associated with the separation of the model DEJ at 0.268 ± 0.057 kPa. When we benchmarked this measure of adhesive strength with that of the model DEJ fabricated with cells of individuals with RDEB, the yield stress was significantly lower (0.153 ± 0.064 kPa) consistent with our current mechanistic understanding of RDEB. In summary, a 3D in vitro model DEJ was developed for quantification of mechanical adhesion between epidermal‐ and dermal‐mimicking layers, which can be utilized for assessment of mechanical adhesion of the model DEJ applicable for Epidermolysis Bullosa‐associated therapeutics. © 2018 The Authors. Journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3231–3238, 2018.

Surface patterning of a novel PEG-functionalized poly-l-lactide polymer to improve its biocompatibility: Applications to bioresorbable vascular stents.

Today, research in the field of bioresorbable vascular stents (BVS) not only focusses on a new material being nontoxic but also tries to enhance its biocompatibility in terms of endothelialization potential and hemocompatibility. To this end, we used picosecond laser ablation technology as a single‐step and contactless method for surface microstructuring of a bioresorbable polymer which can be utilized in stent manufacture. The method works on all materials via fast material removal, can be easily adapted for micropatterning of tubular or more complex sample shapes and scaled up by means of micropatterning of metal molds for manufacturing. Here, picosecond laser ablation was applied to a bioresorbable, biologically inactive and polyethylene glycol‐modified poly‐l‐lactide polymer (PEGylated PLLA) to generate parallel microgrooves with varying geometries. The different patterns were thoroughly evaluated by a series of cyto‐ and hemocompatibility tests revealing that all surfaces were non‐toxic and non‐hemolytic. More importantly, patterns with 20 to 25 µm wide and 6 to 7 µm deep grooves significantly enhanced endothelial cell adhesion in comparison to samples with smaller grooves. Here, human cardiac microvascular endothelial cells were found to align along the groove direction, which is thought to encourage endothelialization of intraluminal surfaces of BVS. © 2018 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 00B: 000–000, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 624–634, 2019.

Extracellular matrix-based materials for regenerative medicine

In tissue engineering and regenerative medicine, a biomaterial provides mechanical support and biochemical signals to encourage cell attachment and modulate cell behaviour. Nature’s template for a biomaterial is the extracellular matrix (ECM). The ECM contains intrinsic biochemical and mechanical cues that regulate cell phenotype and function in development, in homeostasis and in response to injury. The use of ECM-based materials in biomedical research has advanced from coating cell culture plates with purified ECM components to the design of ECM-mimicking biomaterials and the engineering of decellularized tissues aimed at recapitulating the dynamics, composition and structure of the ECM. In this Review, we highlight important matrix properties and functions in the context of tissue engineering and regenerative medicine, consider techniques such as proteomics for the investigation of matrix structure and composition and discuss different engineering strategies for the design of matrix-mimicking biomaterials. Tissue, whole organ and cell culture decellularization approaches are examined for their potential to preserve the tissue-specific biochemical composition and ultrastructure of the ECM and for the development of biomaterials that promote the formation of functional tissues in clinical applications. Finally, we investigate challenges and opportunities of ECM biomaterials for the design of organotypic models to study disease progression, for the ex vivo creation of engineered tissue and for the clinical translation of functional tissue reconstruction strategies in vivo. The extracellular matrix is nature’s template for an ideal biomaterial to guide tissue homeostasis and repair. In this Review, matrix-mimicking biomaterials and decellularized matrices are discussed for their potential to reconstruct and repair tissues in vitro and in vivo.

Neurotrophin-3 released from implant of tissue-engineered fibroin scaffolds inhibits inflammation, enhances nerve fiber regeneration, and improves motor function in canine spinal cord injury.

Spinal cord injury (SCI) normally results in cell death, scarring, cavitation, inhibitory molecules release, etc., which are regarded as a huge obstacle to reconnect the injured neuronal circuits because of the lack of effective stimulus. In this study, a functional gelatin sponge scaffold was used to inhibit local inflammation, enhance nerve fiber regeneration, and improve neural conduction in the canine. This scaffold had good porosity and modified with neurotrophin‐3 (NT‐3)/fibroin complex, which showed sustained release in vitro. After the scaffold was transplanted into canine spinal cord hemisection model, hindlimb movement, and neural conduction were improved evidently. Migrating host cells, newly formed neurons with associated synaptic structures together with functional blood vessels with intact endothelium in the regenerating tissue were identified. Taken together, the results demonstrated that using bioactive scaffold could establish effective microenvironment stimuli for endogenous regeneration, providing a potential and practical strategy for treatment of spinal cord injury. © 2018 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2158‐2170, 2018.

Sea Anemones as Potential Source for Bioactive Metabolites

Marine organisms are novel sources for biologically active compounds which are potentially valuable materials in biomedical research. In the present investigation, the potential bioactive compounds were isolated from the sea anemone Heteractis aurora collected from Mandapam, Southeast coast India. The maximum inhibition zone was found against bacterial pathogens (Klebsiella oxytoca 7.2 ± 1.5 and Escherichia coli 8.1 ± 0.2) followed by fungal pathogens (Botrytis cinerea 5.3 ± 0.5 and Trichoderma koning 4.2 ± 1.2). The antioxidant activity was found to be 42.2 ± 1.14%, whereas hemolytic activity was recorded as 64 Hemolytic unit against chicken blood erythrocytes. The chemical characterizations of sea anemone extract were carried out by FT-IR, GC–MS and NMR (13C, 1H) spectroscopy. The FT-IR results showed the presence of phenyl ring: C–CH3 and C=C stretching. GC–MS analysis revealed the presence of acetic acid-17-acetoxy-4,4,10,13-tetramethyl-7-oxo-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta (a) phenanthren-3-yl (ester) and 4[-4-diethylamino-1-methylbutylamino]-1,2 dimethoxy-6-bromonaphthalene. These identified compounds were subjected for molecular docking analysis against the target protein enoyl-acyl carrier protein reductase which revealed that acetic acid-17-acetoxy-4,4,10,13-tetramethyl-7-oxo-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta (a) phenanthren-3-yl showed better docking interaction than the commercial standard drug Tryptanthrine.

Issue Information

Journal of Biomedical Materials Research Part AVolume 106, Issue 5 p. 1149-1154 Issue InformationFree Access Issue Information First published: 28 March 2018 https://doi.org/10.1002/jbm.a.36396AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume106, Issue5May 2018Pages 1149-1154 RelatedInformation

The optimization and production of stable homogeneous amine enriched surfaces with characterized nanotopographical properties for enhanced osteoinduction of mesenchymal stem cells.

Silane modification has been proposed as a powerful biomaterial surface modification tool. This is the first comprehensive investigation into the effect of silane chain length on the resultant properties of -NH2 silane monolayers and the associated osteoinductive properties of the surface. A range of -NH2 presenting silanes, chain length 3-11, were introduced to glass coverslips and characterized using water contact angles, atomic force microscopy, X-ray photoelectron spectroscopy, and Ninhydrin assays. The ability of the variation in chain length to form a homogenous layer across the entirety of the surfaces was also assessed. The osteoinductive potential of the resultant surfaces was evaluated by real-time polymerase chain reaction, immunocytochemistry, and von Kossa staining. Control of surface chemistry and topography was directly associated with changes in chain length. This resulted in the identification of a specific, chain length 11 (CL11) which significantly increased the osteoinductive properties of the modified materials. Only CL11 surfaces had a highly regular nano-topography/roughness which resulted in the formation of an appetite-like layer on the surface that induced a significantly enhanced osteoinductive response (increased expression of osteocalcin, CBFA1, sclerostin, and the production of a calcified matrix) across the entirety of the surface. © 2018 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1862-1877, 2018.

Fatigue and quasi-static mechanical behavior of bio-degradable porous biomaterials based on magnesium alloys.

Magnesium and its alloys have the intrinsic capability of degrading over time in vivo without leaving toxic degradation products. They are therefore suitable for use as biodegradable scaffolds that are replaced by the regenerated tissues. One of the main concerns for such applications, particularly in load‐bearing areas, is the sufficient mechanical integrity of the scaffold before sufficient volumes of de novo tissue is generated. In the majority of the previous studies on the effects of biodegradation on the mechanical properties of porous biomaterials, the change in the elastic modulus has been studied. In this study, variations in the static and fatigue mechanical behavior of porous structures made of two different Mg alloys (AZ63 and M2) over different dissolution times ( 6, 12, and 24 h) have been investigated. The results showed an increase in the mechanical properties obtained from stress–strain curve (elastic modulus, yield stress, plateau stress, and energy absorption) after 6–12 h and a sharp decrease after 24 h. The initial increase in the mechanical properties may be attributed to the accumulation of corrosion products in the pores of the porous structure before degradation has considerably proceeded. The effects of mineral deposition was more pronounced for the elastic modulus as compared to other mechanical properties. That may be due to insufficient integration of the deposited particles in the structure of the magnesium alloys. While the bonding of the parts being combined in a composite‐like material is of great importance in determining its yield stress, the effects of bonding strength of both parts is much lower in determining the elastic modulus. The results of the current study also showed that the dissolution rates of the studied Mg alloys were too high for direct use in human body. © 2018 Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1798–1811, 2018.

Bioactivity and composition of a preserved connective tissue matrix derived from human placental tissue

There are a wide variety of extracellular matrices that can be used for regenerative purposes. Placental tissue‐based matrices are quickly becoming an attractive option given the availability of the tissue source and the wide variety of bioactive molecules knows to exist in unprocessed placental tissues. As fresh placental tissues are seldom an option at the point of care, we examined both the composition and bioactivity of a commercially packaged flowable placental connective tissue matrix (FPTM) (BioECM®, Skye Biologics, Inc.) that was preserved by the proprietary HydraTek® process. The FPTM contained significant amounts of collagen and various growth factors such as bFGF, EGF, PDGF, KGF, and PIGF. In addition, it contained high levels of tissue inhibitors of metalloproteinases (TIMP‐1 and 2) and molecules known to modulate the immune response including TGF‐β and IL‐4. In terms of its bioactivity, the FPTM displayed the ability (1) to suppress INF‐γ secretion in activated T‐cells nearly fourfold over control media, (2) to inhibit methicillin resistant Staphylococcus aureus (MRSA) and Staphylococcus saprophyticus proliferation, (3) to increase the migration of adipose‐derived stem cells (ASCs) nearly threefold over control media and (4) to adhere to ASCs in culture. When ASCs were exposed to FPTM in culture, the cells maintained healthy morphology and showed no significant changes in the expression of five genes involved in tissue growth and repair as compared to culture in standard growth media. © 2018 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2731–2740, 2018.