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Metabolic glycan labeling and chemoselective functionalization of native biomaterials

Ren X, Evangelista-Leite D, Wu T, Rajab TK, Moser PT, Kitano K, et al.

Biomaterials, 2018 11;182:127-134.
PMID: 30118980 DOI: 10.1016/j.biomaterials.2018.08.012

Decellularized native extracellular matrix (ECM) biomaterials are widely used in tissue engineering and have reached clinical application as biomesh implants. To enhance their regenerative properties and postimplantation performance, ECM biomaterials could be functionalized via immobilization of bioactive molecules. To facilitate ECM functionalization, we developed a metabolic glycan labeling approach using physiologic pathways to covalently incorporate click-reactive azide ligands into the native ECM of a wide variety of rodent tissues and organs in vivo, and into the ECM of isolated rodent and porcine lungs cultured ex vivo. The incorporated azides within the ECM were preserved after decellularization and served as chemoselective ligands for subsequent bioconjugation via click chemistry. As proof of principle, we generated alkyne-modified heparin, immobilized it onto azide-incorporated acellular lungs, and demonstrated its bioactivity by Antithrombin III immobilization and Factor Xa inhibition. The herein reported metabolic glycan labeling approach represents a novel platform technology for manufacturing click-reactive native ECM biomaterials, thereby enabling efficient and chemoselective functionalization of these materials to facilitate tissue regeneration and repair.

Matched MeSH terms: Biocompatible Materials/chemistry*
Fulltext In Vitro Study of Surface Modified Poly(ethylene glycol)-Impregnated Sintered Bovine Bone Scaffolds on Human Fibroblast Cells

Pramanik S, Ataollahi F, Pingguan-Murphy B, Oshkour AA, Osman NAA

Sci Rep, 2015 May 07;5:9806.
PMID: 25950377 DOI: 10.1038/srep09806

Scaffold design from xenogeneic bone has the potential for tissue engineering (TE). However, major difficulties impede this potential, such as the wide range of properties in natural bone. In this study, sintered cortical bones from different parts of a bovine-femur impregnated with biodegradable poly(ethylene glycol) (PEG) binder by liquid phase adsorption were investigated. Flexural mechanical properties of the PEG-treated scaffolds showed that the scaffold is stiffer and stronger at a sintering condition of 1000°C compared with 900°C. In vitro cytotoxicity of the scaffolds evaluated by Alamar Blue assay and microscopic tests on human fibroblast cells is better at 1000°C compared with that at 900°C. Furthermore, in vitro biocompatibility and flexural property of scaffolds derived from different parts of a femur depend on morphology and heat-treatment condition. Therefore, the fabricated scaffolds from the distal and proximal parts at 1000°C are potential candidates for hard and soft TE applications, respectively.

Matched MeSH terms: Biocompatible Materials/chemistry
Fulltext Mechanical and in vitro biological performance of graphene nanoplatelets reinforced calcium silicate composite

Mehrali M, Moghaddam E, Seyed Shirazi SF, Baradaran S, Mehrali M, Latibari ST, et al.

PLoS One, 2014;9(9):e106802.
PMID: 25229540 DOI: 10.1371/journal.pone.0106802

Calcium silicate (CaSiO3, CS) ceramic composites reinforced with graphene nanoplatelets (GNP) were prepared using hot isostatic pressing (HIP) at 1150°C. Quantitative microstructural analysis suggests that GNP play a role in grain size and is responsible for the improved densification. Raman spectroscopy and scanning electron microscopy showed that GNP survived the harsh processing conditions of the selected HIP processing parameters. The uniform distribution of 1 wt.% GNP in the CS matrix, high densification and fine CS grain size help to improve the fracture toughness by ∼130%, hardness by ∼30% and brittleness index by ∼40% as compared to the CS matrix without GNP. The toughening mechanisms, such as crack bridging, pull-out, branching and deflection induced by GNP are observed and discussed. The GNP/CS composites exhibit good apatite-forming ability in the simulated body fluid (SBF). Our results indicate that the addition of GNP decreased pH value in SBF. Effect of addition of GNP on early adhesion and proliferation of human osteoblast cells (hFOB) was measured in vitro. The GNP/CS composites showed good biocompatibility and promoted cell viability and cell proliferation. The results indicated that the cell viability and proliferation are affected by time and concentration of GNP in the CS matrix.

Matched MeSH terms: Biocompatible Materials/chemistry
Synthesis, mechanical properties, and in vitro biocompatibility with osteoblasts of calcium silicate-reduced graphene oxide composites

Mehrali M, Moghaddam E, Shirazi SF, Baradaran S, Mehrali M, Latibari ST, et al.

ACS Appl Mater Interfaces, 2014 Mar 26;6(6):3947-62.
PMID: 24588873 DOI: 10.1021/am500845x

Calcium silicate (CaSiO3, CS) ceramics are promising bioactive materials for bone tissue engineering, particularly for bone repair. However, the low toughness of CS limits its application in load-bearing conditions. Recent findings indicating the promising biocompatibility of graphene imply that graphene can be used as an additive to improve the mechanical properties of composites. Here, we report a simple method for the synthesis of calcium silicate/reduced graphene oxide (CS/rGO) composites using a hydrothermal approach followed by hot isostatic pressing (HIP). Adding rGO to pure CS increased the hardness of the material by ∼40%, the elastic modulus by ∼52%, and the fracture toughness by ∼123%. Different toughening mechanisms were observed including crack bridging, crack branching, crack deflection, and rGO pull-out, thus increasing the resistance to crack propagation and leading to a considerable improvement in the fracture toughness of the composites. The formation of bone-like apatite on a range of CS/rGO composites with rGO weight percentages ranging from 0 to 1.5 has been investigated in simulated body fluid (SBF). The presence of a bone-like apatite layer on the composite surface after soaking in SBF was demonstrated by X-ray diffraction (XRD) and field emission scanning electron microscopy (FESEM). The biocompatibility of the CS/rGO composites was characterized using methyl thiazole tetrazolium (MTT) assays in vitro. The cell adhesion results showed that human osteoblast cells (hFOB) can adhere to and develop on the CS/rGO composites. In addition, the proliferation rate and alkaline phosphatase (ALP) activity of cells on the CS/rGO composites were improved compared with the pure CS ceramics. These results suggest that calcium silicate/reduced graphene oxide composites are promising materials for biomedical applications.

Matched MeSH terms: Biocompatible Materials/chemistry*
Dental implants from functionally graded materials

Mehrali M, Shirazi FS, Mehrali M, Metselaar HS, Kadri NA, Osman NA

J Biomed Mater Res A, 2013 Oct;101(10):3046-57.
PMID: 23754641 DOI: 10.1002/jbm.a.34588

Functionally graded material (FGM) is a heterogeneous composite material including a number of constituents that exhibit a compositional gradient from one surface of the material to the other subsequently, resulting in a material with continuously varying properties in the thickness direction. FGMs are gaining attention for biomedical applications, especially for implants, owing to their reported superior composition. Dental implants can be functionally graded to create an optimized mechanical behavior and achieve the intended biocompatibility and osseointegration improvement. This review presents a comprehensive summary of biomaterials and manufacturing techniques researchers employ throughout the world. Generally, FGM and FGM porous biomaterials are more difficult to fabricate than uniform or homogenous biomaterials. Therefore, our discussion is intended to give the readers about successful and obstacles fabrication of FGM and porous FGM in dental implants that will bring state-of-the-art technology to the bedside and develop quality of life and present standards of care.

Matched MeSH terms: Biocompatible Materials/chemistry*
Biocompatible magnesium-doped biphasic calcium phosphate for bone regeneration

Ballouze R, Marahat MH, Mohamad S, Saidin NA, Kasim SR, Ooi JP

J Biomed Mater Res B Appl Biomater, 2021 Oct;109(10):1426-1435.
PMID: 33484103 DOI: 10.1002/jbm.b.34802

Autologous bone grafting remains the gold standard for almost all bone void-filling orthopedic surgery. However, autologous bone grafting has several limitations, thus scientists are trying to identify an ideal synthetic material as an alternative bone graft substitute. Magnesium-doped biphasic calcium phosphate (Mg-BCP) has recently been in the spotlight and is considered to be a potential bone substitute. The Mg-BCP is a mixture of two bioceramics, that is, hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), doped with Mg2+ , and can be synthesized through chemical wet-precipitation, sol-gel, single diffusion gel, and solid state reactions. Regardless of the synthesis routes, it is found that the Mg2+ preferentially accommodates in β-TCP lattice instead of the HA lattice. The addition of Mg2+ to BCP leads to desirable physicochemical properties and is found to enhance the apatite-forming ability as compared to pristine BCP. In vitro results suggest that the Mg-BCP is bioactive and not toxic to cells. Implantation of Mg-BCP in in vivo models further affirmed its biocompatibility and efficacy as a bone substitute. However, like the other bioceramics, the optimum physicochemical properties of the Mg-BCP scaffold have yet to be determined. Further investigations are required regarding Mg-BCP applications in bone tissue engineering.

Matched MeSH terms: Biocompatible Materials/chemistry*
Sustained-release alginate-chitosan pellets prepared by melt pelletization technique

Wong TW, Nurulaini H

Drug Dev Ind Pharm, 2012 Dec;38(12):1417-27.
PMID: 22309449 DOI: 10.3109/03639045.2011.653364

Alginate-chitosan pellets prepared by extrusion-spheronization technique exhibited fast drug dissolution.

Matched MeSH terms: Biocompatible Materials/chemistry*
Mineral and physichocemical characterization of cockle (Anadara granosa) shells as an alternative biomaterial for bone tissue engineering

Hazmi AJ, Zuki AB, Noordin MM, Jalila A, Norimah Y

Med J Malaysia, 2008 Jul;63 Suppl A:93-4.
PMID: 19025000

This study was conducted based on the hypothesis that mineral and physicochemical properties of cockle shells similarly resemble the properties of corals (Porites sp.). Hence, the mineral and physicochemical evaluations of cockle shells were conducted to support the aforementioned hypothesis. The results indicated that cockle shells and coral exoskeleton shared similar mineral and physicochemical properties.

Matched MeSH terms: Biocompatible Materials/chemistry
γ-Fe2O3 nanoparticles filled polyvinyl alcohol as potential biomaterial for tissue engineering scaffold

Ngadiman NH, Idris A, Irfan M, Kurniawan D, Yusof NM, Nasiri R

J Mech Behav Biomed Mater, 2015 Sep;49:90-104.
PMID: 26002419 DOI: 10.1016/j.jmbbm.2015.04.029

Maghemite (γ-Fe2O3) nanoparticle with its unique magnetic properties is recently known to enhance the cell growth rate. In this study, γ-Fe2O3 is mixed into polyvinyl alcohol (PVA) matrix and then electrospun to form nanofibers. Design of experiments was used to determine the optimum parameter settings for the electrospinning process so as to produce elctrospun mats with the preferred characteristics such as good morphology, Young's modulus and porosity. The input factors of the electrospinnning process were nanoparticles content (1-5%), voltage (25-35 kV), and flow rate (1-3 ml/h) while the responses considered were Young's modulus and porosity. Empirical models for both responses as a function of the input factors were developed and the optimum input factors setting were determined, and found to be at 5% nanoparticle content, 35 kV voltage, and 1 ml/h volume flow rate. The characteristics and performance of the optimum PVA/γ-Fe2O3 nanofiber mats were compared with those of neat PVA nanofiber mats in terms of morphology, thermal properties, and hydrophilicity. The PVA/γ-Fe2O3 nanofiber mats exhibited higher fiber diameter and surface roughness yet similar thermal properties and hydrophilicity compared to neat PVA PVA/γ-Fe2O3 nanofiber mats. Biocompatibility test by exposing the nanofiber mats with human blood cells was performed. In terms of clotting time, the PVA/γ-Fe2O3 nanofibers exhibited similar behavior with neat PVA. The PVA/γ-Fe2O3 nanofibers also showed higher cells proliferation rate when MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was done using human skin fibroblast cells. Thus, the PVA/γ-Fe2O3 electrospun nanofibers can be a promising biomaterial for tissue engineering scaffolds.

Matched MeSH terms: Biocompatible Materials/chemistry*
Fulltext Preparation and properties of poly(vinyl alcohol)/chitosan blend bionanocomposites reinforced with cellulose nanocrystals/ZnO-Ag multifunctional nanosized filler

Azizi S, Ahmad MB, Hussein MZ, Ibrahim NA, Namvar F

Int J Nanomedicine, 2014;9:1909-17.
PMID: 24790433 DOI: 10.2147/IJN.S60274

A series of novel bionanocomposites were cast using different contents of zinc oxide-silver nanoparticles (ZnO-AgNPs) stabilized by cellulose nanocrystals (CNC) as multifunctional nanosized fillers in poly(vinyl alcohol)/chitosan (PVA/Cs) matrices. The morphological structure, mechanical properties, ultraviolet-visible absorption, and antimicrobial properties of the prepared films were investigated as a function of their CNC/ZnO-AgNP content and compared with PVA/chitosan/CNC bionanocomposite films. X-ray diffraction and field emission scanning electron microscopic analyses showed that the CNC/ZnO-AgNPs were homogeneously dispersed in the PVA/Cs matrix and the crystallinity increased with increasing nanosized filler content. Compared with pure PVA/Cs, the tensile strength and modulus in the films increased from 0.055 to 0.205 GPa and from 0.395 to 1.20 GPa, respectively. Ultraviolet and visible light can be efficiently absorbed by incorporating ZnO-AgNPs into a PVA/Cs matrix, suggesting that these bionanocomposite films show good visibility and ultraviolet-shielding effects. The bionanocomposite films had excellent antimicrobial properties, killing both Gram-negative Salmonella choleraesuis and Gram-positive Staphylococcus aureus. The enhanced physical properties achieved by incorporating CNC/ZnO-AgNPs could be beneficial in various applications.

Matched MeSH terms: Biocompatible Materials/chemistry
Improved cellular response of chemically crosslinked collagen incorporated hydroxyethyl cellulose/poly(vinyl) alcohol nanofibers scaffold

Zulkifli FH, Jahir Hussain FS, Abdull Rasad MS, Mohd Yusoff M

J Biomater Appl, 2015 Feb;29(7):1014-27.
PMID: 25186524 DOI: 10.1177/0885328214549818

The aim of this research is to develop biocompatible nanofibrous mats using hydroxyethyl cellulose with improved cellular adhesion profiles and stability and use these fibrous mats as potential scaffold for skin tissue engineering. Glutaraldehyde was used to treat the scaffolds water insoluble as well as improve their biostability for possible use in biomedical applications. Electrospinning of hydroxyethyl cellulose (5 wt%) with poly(vinyl alcohol) (15 wt%) incorporated with and without collagen was blended at (1:1:1) and (1:1) ratios, respectively, and was evaluated for optimal criteria as tissue engineering scaffolds. The nanofibrous mats were crosslinked and characterized by scanning electron microscope, Fourier transform infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. Scanning electron microscope images showed that the mean diameters of blend nanofibers were gradually increased after chemically crosslinking with glutaraldehyde. Fourier transform infrared spectroscopy was carried out to understand chemical interactions in the presence of aldehyde groups. Thermal characterization results showed that the stability of hydroxyethyl cellulose/poly(vinyl alcohol) and hydroxyethyl cellulose/poly(vinyl alcohol)/collagen nanofibers was increased with glutaraldehyde treatment. Studies on cell-scaffolds interaction were carried out by culturing human fibroblast (hFOB) cells on the nanofibers by assessing the growth, proliferation, and morphologies of cells. The scanning electron microscope results show that better cell proliferation and attachment appeared on hydroxyethyl cellulose/poly(vinyl alcohol)/collagen substrates after 7 days of culturing, thus, promoting the potential of electrospun scaffolds as a promising candidate for tissue engineering applications.

Matched MeSH terms: Biocompatible Materials/chemistry
Preparation and characterization of a novel biocomposite based on duck feet gelatin as alternative to bovine gelatin

Abedinia A, Ariffin F, Huda N, Mohammadi Nafchi A

Int J Biol Macromol, 2018 Apr 01;109:855-862.
PMID: 29133087 DOI: 10.1016/j.ijbiomac.2017.11.051

Edible duck feet gelatin (DFG)-based biocomposites with different glycerol (GLY) contents (15%, 25%, and 35% of dried DFG) were prepared. Physicochemical, mechanical, barrier, and heat seal properties of DFG films were characterized and compared as an alternative to bovine gelatin film. Increasing glycerol from 15 to 35% decreased the TS and YM and EB and HS increased, in value of 42.54-7.27 and 1240-157.10MPa and 22.82-50.33% and 42.06-347.15N/m respectively. The water vapor permeability (WVP) and oxygen permeability (OP) of films were increased from 4.78 to 5.6×10-11gm-1Pa-1s-1 and from 3.97 to 33.99cm3mμ/m2 d kPa respectively. GAB model estimations showed monolayer water content of films increased with the increase of plasticizer content. Moisture sorption isotherm modelling exhibited a type II BET classification. Fourier transform infrared (FTIR) spectra showed shifted peak at approximately 1024cm-1, which was related to glycerol. The results show that the properties of DFG film are suitable for use as an alternative material to bovine gelatin film.

Matched MeSH terms: Biocompatible Materials/chemistry*
Porous alumina-hydroxyapatite composites through protein foaming-consolidation method

Sopyan I, Fadli A, Mel M

J Mech Behav Biomed Mater, 2012 Apr;8:86-98.
PMID: 22402156 DOI: 10.1016/j.jmbbm.2011.10.012

This report presents physical characterization and cell culture test of porous alumina-hydroxyapatite (HA) composites fabricated through protein foaming-consolidation technique. Alumina and HA powders were mixed with yolk and starch at an adjusted ratio to make slurry. The resulting slip was poured into cylindrical shaped molds and followed by foaming and consolidation via 180 °C drying for 1 h. The obtained green bodies were burned at 600 °C for 1 h, followed by sintering at temperatures of 1200-1550 °C for 2 h. Porous alumina-HA bodies with 26-77 vol.% shrinkage, 46%-52% porosity and 0.1-6.4 MPa compressive strength were obtained. The compressive strength of bodies increased with the increasing sintering temperatures. The addition of commercial HA in the body was found to increase the compressive strength, whereas the case is reverse for sol-gel derived HA. Biocompatibility study of porous alumina-HA was performed in a stirred tank bioreactor using culture of Vero cells. A good compatibility of the cells to the porous microcarriers was observed as the cells attached and grew at the surface of microcarriers at 8-120 cultured hours. The cell growth on porous alumina microcarrier was 0.015 h(-1) and increased to 0.019 h(-1) for 0.3 w/w HA-to-alumina mass ratio and decreased again to 0.017 h(-1) for 1.0 w/w ratio.

Matched MeSH terms: Biocompatible Materials/chemistry*
Synthesis and characterization of magnesium doped biphasic calcium phosphate

Toibah AR, Sopyan I, Mel M

Med J Malaysia, 2008 Jul;63 Suppl A:83-4.
PMID: 19024995

The incorporation of magnesium ions into the calcium phosphate structure is of great interest for the development of artificial bone implants. This paper investigates the preparation of magnesium-doped biphasic calcium phosphate (Mg-BCP) via sol gel method at various concentrations of added Mg. The effect of calcinations temperature (ranging from 500 degrees C to 900 degrees C) and concentrations of Mg incorporated into BCP has been studied by the aid of XRD, TGA and infrared spectroscopy (IR) in transmittance mode analysis. The study indicated that the powder was pure BCP and Mg-BCP with 100% purity and high crystallinity. The results also indicated that beta-tricalcium phosphate (beta-TCP) phase can be observed when the powder was calcined at 800 degrees C and above.

Matched MeSH terms: Biocompatible Materials/chemistry
Classification, processing and application of hydrogels: A review

Ullah F, Othman MB, Javed F, Ahmad Z, Md Akil H

Mater Sci Eng C Mater Biol Appl, 2015 Dec 1;57:414-33.
PMID: 26354282 DOI: 10.1016/j.msec.2015.07.053

This article aims to review the literature concerning the choice of selectivity for hydrogels based on classification, application and processing. Super porous hydrogels (SPHs) and superabsorbent polymers (SAPs) represent an innovative category of recent generation highlighted as an ideal mould system for the study of solution-dependent phenomena. Hydrogels, also termed as smart and/or hungry networks, are currently subject of considerable scientific research due to their potential in hi-tech applications in the biomedical, pharmaceutical, biotechnology, bioseparation, biosensor, agriculture, oil recovery and cosmetics fields. Smart hydrogels display a significant physiochemical change in response to small changes in the surroundings. However, such changes are reversible; therefore, the hydrogels are capable of returning to its initial state after a reaction as soon as the trigger is removed.

Matched MeSH terms: Biocompatible Materials/chemistry*
Synthesis and functionalization of chitosan built hydrogel with induced hydrophilicity for extended release of sparingly soluble drugs

Ullah F, Javed F, Othman MBH, Khan A, Gul R, Ahmad Z, et al.

J Biomater Sci Polym Ed, 2018 03;29(4):376-396.
PMID: 29285989 DOI: 10.1080/09205063.2017.1421347

Addressing the functional biomaterials as next-generation therapeutics, chitosan and alginic acid were copolymerized in the form of chemically crosslinked interpenetrating networks (IPNs). The native hydrogel was functionalized via carbodiimide (EDC), catalyzed coupling of soft ligand (1,2-Ethylenediamine) and hard ligand (4-aminophenol) to replace -OH groups in alginic acid units for extended hydrogel- interfaces with the aqueous and sparingly soluble drug solutions. The chemical structure, Lower solution critical temperature (LCST ≈ 37.88 °C), particle size (Zh,app ≈ 150-200 nm), grain size (160-360 nm), surface roughness (85-250 nm), conductivity (37-74 mv) and zeta potential (16-32 mv) of native and functionalized hydrogel were investigated by using FT-IR, solid state-13C-NMR, TGA, DSC, FESEM, AFM and dynamic light scattering (DLS) measurements. The effective swelling, drug loading (47-78%) and drug release (53-86%) profiles were adjusted based on selective functionalization of hydrophobic IPNs due to electrostatic complexation and extended interactions of hydrophilic ligands with the aqueous and drug solutions. Drug release from the hydrogel matrices with diffusion coefficient n ≈ 0.7 was established by Non- Fickian diffusion mechanism. In vitro degradation trials of the hydrogel with a 20% loss of wet mass in simulated gastric fluid (SGF) and 38% loss of wet mass in simulated intestinal fluid (SIF), were investigated for 400 h through bulk erosion. Consequently, a slower rate of drug loading and release was observed for native hydrogel, due to stronger H-bonding, interlocking and entanglement within the IPNs, which was finely tuned and extended by the induced hydrophilic and functional ligands. In the light of induced hydrophilicity, such functional hydrogel could be highly attractive for extended release of sparingly soluble drugs.

Matched MeSH terms: Biocompatible Materials/chemistry
Influence of citric acid on the physical and biomineralization ability of freeze/thaw poly(vinyl alcohol) hydrogel

Wahid MNA, Abd Razak SI, Abdul Kadir MR, Hassan R, Nayan NHM, Mat Amin KA

J Biomater Appl, 2018 07;33(1):94-102.
PMID: 29716417 DOI: 10.1177/0885328218771195

This work reports the modification of freeze/thaw poly(vinyl alcohol) hydrogel using citric acid as the bioactive molecule for hydroxyapatite formation in simulated body fluid. Inclusion of 1.3 mM citric acid into the poly(vinyl alcohol) hydrogel showed that the mechanical strength, crystalline phase, functional groups and swelling ability were still intact. Adding citric acid at higher concentrations (1.8 and 2.3 mM), however, resulted in physically poor hydrogels. Presence of 1.3 mM of citric acid showed the growth of porous hydroxyapatite crystals on the poly(vinyl alcohol) surface just after one day of immersion in simulated body fluid. Meanwhile, a fully covered apatite layer on the poly(vinyl alcohol) surface plus the evidence of apatite forming within the hydrogel were observed after soaking for seven days. Gel strength of the soaked poly(vinyl alcohol)/citric acid-1.3 mM hydrogel revealed that the load resistance was enhanced compared to that of the neat poly(vinyl alcohol) hydrogel. This facile method of inducing rapid growth of hydroxyapatite on the hydrogel surface as well as within the hydrogel network can be useful for guided bone regenerative materials.

Matched MeSH terms: Biocompatible Materials/chemistry*
Fulltext In vitro cellular localization and efficient accumulation of fluorescently tagged biomaterials from monodispersed chitosan nanoparticles for elucidation of controlled release pathways for drug delivery systems

Hassan UA, Hussein MZ, Alitheen NB, Yahya Ariff SA, Masarudin MJ

Int J Nanomedicine, 2018;13:5075-5095.
PMID: 30233174 DOI: 10.2147/IJN.S164843

Background: Inefficient cellular delivery and poor intracellular accumulation are major drawbacks towards achieving favorable therapeutic responses from many therapeutic drugs and biomolecules. To tackle this issue, nanoparticle-mediated delivery vectors have been aptly explored as a promising delivery strategy capable of enhancing the cellular localization of biomolecules and improve their therapeutic efficacies. However, the dynamics of intracellular biomolecule release and accumulation from such nanoparticle systems has currently remained scarcely studied.
Objectives: The objective of this study was to utilize a chitosan-based nanoparticle system as the delivery carrier for glutamic acid, a model for encapsulated biomolecules to visualize the in vitro release and accumulation of the encapsulated glutamic acid from chitosan nanoparticle (CNP) systems.
Methods: CNP was synthesized via ionic gelation routes utilizing tripolyphosphate (TPP) as a cross-linker. In order to track glutamic acid release, the glutamic acid was fluorescently-labeled with fluorescein isothiocyanate prior encapsulation into CNP.
Results: Light Scattering data concluded the successful formation of small-sized and mono-dispersed CNP at a specific volume ratio of chitosan to TPP. Encapsulation of glutamic acid as a model cargo into CNP led to an increase in particle size to >100 nm. The synthesized CNP exhibited spherical shape under Electron Microscopy. The formation of CNP was reflected by the reduction in free amine groups of chitosan following ionic crosslinking reactions. The encapsulation of glutamic acid was further confirmed by Fourier Transform Infrared (FTIR) analysis. Cell viability assay showed 70% cell viability at the maximum concentration of 0.5 mg/mL CS and 0.7 mg/mL TPP used, indicating the low inherent toxicity property of this system. In vitro release study using fluorescently-tagged glutamic acids demonstrated the release and accumulation of the encapsulated glutamic acids at 6 hours post treatment. A significant accumulation was observed at 24 hours and 48 hours later. Flow cytometry data demonstrated a gradual increase in intracellular fluorescence signal from 30 minutes to 48 hours post treatment with fluorescently-labeled glutamic acids encapsulated CNP.
Conclusion: These results therefore suggested the potential of CNP system towards enhancing the intracellular delivery and release of the encapsulated glutamic acids. This CNP system thus may serves as a potential candidate vector capable to improve the therapeutic efficacy for drugs and biomolecules in medical as well as pharmaceutical applications through the enhanced intracellular release and accumulation of the encapsulated cargo.

Matched MeSH terms: Biocompatible Materials/chemistry
In vitro evaluation of actively targetable superparamagnetic nanoparticles to the folate receptor positive cancer cells

Nasiri R, Hamzehalipour Almaki J, Idris AB, Abdul Majid FA, Nasiri M, Salouti M, et al.

Mater Sci Eng C Mater Biol Appl, 2016 Dec 01;69:1147-58.
PMID: 27612812 DOI: 10.1016/j.msec.2016.07.076

Engineering of a physiologically compatible, stable and targetable SPIONs-CA-FA formulation was reported. Initially fabricated superparamagnetic iron oxide nanoparticles (SPIONs) were coated with citric acid (CA) to hamper agglomeration as well as to ameliorate biocompatibility. Folic acid (FA) as a targeting agent was then conjugated to the citric acid coated SPIONs (SPIONs-CA) for targeting the specific receptors expressed on the FAR+ cancer cells. Physiochemical characterizations were then performed to assure required properties like stability, size, phase purity, surface morphology, chemical integrity and magnetic properties. In vitro evaluations (MTT assay) were performed on HeLa, HSF 1184, MDA-MB-468 and MDA-MB-231cell lines to ensure the biocompatibility of SPIONs-CA-FA. There were no morphological changes and lysis in contact with erythrocytes recorded for SPIONs-CA-FA and SPIONs-CA. High level of SPIONs-CA-FA binding to FAR+ cell lines was assured via qualitative and quantitative in vitro binding studies. Hence, SPIONs-CA-FA was introduced as a promising tool for biomedical applications like magnetic hyperthermia and drug delivery. The in vitro findings presented in this study need to be compared with those of in vivo studies.

Matched MeSH terms: Biocompatible Materials/chemistry*
Polydopamine as an intermediate layer for silver and hydroxyapatite immobilisation on metallic biomaterials surface

Saidin S, Chevallier P, Abdul Kadir MR, Hermawan H, Mantovani D

Mater Sci Eng C Mater Biol Appl, 2013 Dec 1;33(8):4715-24.
PMID: 24094179 DOI: 10.1016/j.msec.2013.07.026

Hydroxyapatite (HA) coated implant is more susceptible to bacterial infection as the micro-structure surface which is beneficial for osseointegration, could also become a reservoir for bacterial colonisation. The aim of this study was to introduce the antibacterial effect of silver (Ag) to the biomineralised HA by utilising a polydopamine film as an intermediate layer for Ag and HA immobilisation. Sufficient catechol groups in polydopamine were required to bind chemically stainless steel 316 L, Ag and HA elements. Different amounts of Ag nanoparticles were metallised on the polydopamine grafted stainless steel by varying the immersion time in silver nitrate solution from 12 to 24 h. Another polydopamine layer was then formed on the metallised film, followed by surface biomineralisation in 1.5 Simulated Body Fluid (SBF) solution for 3 days. Several characterisation techniques including X-Ray Photoelectron Spectroscopy, Atomic Force Microscopy, Scanning Electron Microscopy and Contact Angle showed that Ag nanoparticles and HA agglomerations were successfully immobilised on the polydopamine film through an element reduction process. The Ag metallisation at 24 h has killed the viable bacteria with 97.88% of bactericidal ratio. The Ag was ionised up to 7 days which is crucial to prevent bacterial infection during the first stage of implant restoration. The aged functionalised films were considered stable due to less alteration of its chemical composition, surface roughness and wettability properties. The ability of the functionalised film to coat complex and micro scale metal make it suitable for dental and orthopaedic implants application.

Matched MeSH terms: Biocompatible Materials/chemistry*

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