LAPONITE A VERSATILE COMPONENT IN HYBRID MATERIALS …

Memoirs of the Scientific Sections of the Romanian Academy

Tome XLIII, 2020

CHEMISTRY

LAPONITE® – A VERSATILE COMPONENT IN HYBRID

MATERIALS FOR BIOMEDICAL APPLICATIONS

SIMONA MORARIU and MIRELA TEODORESCU

“Petru Poni” Institute of Macromolecular Chemistry, Iasi, Romania Corresponding author: [email protected]

This paper is dedicated to the memory of Acad. Cristofor I. Simionescu (1920–2007)

and to the commemorative celebration of the centenary of his birth.

The versatility of Laponite® (LAP), given by its layered structure, makes it one of the most investigated and used clays. LAP is a synthetic cationic clay, from the smectite class, with particles size of 25–30 nm in diameter and about 1 nm thickness. This clay is biocompatible, bioactive and has the capacity to swell in water, to adsorb/ desorb large or small molecules, to adhere to cells favouring their growth, to improve the mechanical toughness of the materials in which it is incorporated, etc. The aim of this brief review is to present the most recent and relevant data concerning the structure and properties of LAP and its use in designing drug delivery systems, wound dressings, tissue engineering/ regenerative materials, biosensors and other advanced recent applications, such as 3D printing for fabrication of scaffolds, and nanomedicine for diagnosis and treatment.

Keywords: Laponite®, drug delivery, tissue engineering, regenerative medicine, biosensor

1. INTRODUCTION

In latest years, smectite clays have attracted tremendous attention of scientists for new systems design, due to their low cost, large availability and properties induced to the material that encompasses them [1].

The high adsorption capacity and high ability to cationic exchange are important properties of smectite clays for their application in cosmetics, household cleaners, pharmaceutical and medical field.

Laponite (LAP) is a synthetic smectite clay preferred to natural clay in the realization of new materials for biomedical and cosmetic applications, due to its high purity and thickening properties [2].

By its incorporation into responsive polymeric hydrogels, drug delivery systems or biosensors can be prepared, due to its capacity to adsorb/ desorb water under a stimulus influence. The presence of LAP nanoparticles into hydrogel strengthens the polymer network by establishing additional physical interactions between polymer chains and clay particles. Such reinforcement of polymer

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Simona Morariu and Mirela Teodorescu 20 142

network improves the mechanical properties of hydrogels, recommending their application as wound dressings, tissue scaffolds and artificial tissues. It is known that LAP addition increases hydrogel surface roughness, granting a good adhesivity to soft tissues or skin, a property required in developing wound dressing materials.

The present paper makes a brief presentation of the recent advanced hybrid systems based on LAP, applicable in biomedical fields (i.e., drug delivery, tissue engineering, regenerative medicine, wound dressings, biosensors). A short description of LAP structure is also presented in the first part of the paper, in order to understand the role of clay in the further mentioned hybrid nanocomposites.

2. LAPONITE® STRUCTURE

Laponite®

(BYK Additives Ltd), with chemical formula Na0.7[(Si8Mg5.5Li0.3)O20(OH)4], belongs to 2:1 phyllosilicates, having a crystal structure formed of a magnesium octahedral sheet between two silicon tetrahedron sheets (Fig. 1a) [3]. Some magnesium ions (Mg

2+) are partially substituted with

lithium (Li+) and the surface of clay platelets is negatively charged. LAP primary

particles have disc-like shapes, with thickness and diameter about 1 nm and 25–30

nm, respectively. A single LAP platelet is constituted of about 1,100 100 unit

cells, corresponding to a molecular weight of 7105 910

5 g/mol [4,5]. LAP

primary discs are stacked and the negative charges on particles surface are balanced by the Na

+ ions between interlayers (Fig. 1b).

Fig. 1. Schematic representation of (a) single LAP nanoplatelet

and (b) nanoplatelets exfoliation in water.

2 Laponite® – A versatile component in hybrid materials for biomedical applications 143

These stacks delaminate in water and the clay disperses as individual discs with a strong negative charge on their surface and a weak positive charge on their edges. For LAP concentrations (cLAP) lower than 2% and pH<9, degradation of LAP particles into non-toxic components was observed, according to the following reaction [6]:

Na0.7[(Si8Mg5.5Li0.3)O20(OH)4] + 12H+ + 8H2O

0.7Na

+ + 8Si(OH)4 + 5.5Mg

2+ + 0.3Li

+

LAP aqueous dispersions show a complex phase diagram, about which scientists still debate. Most researchers consider that dispersions with clay concentrations below 3% are initially in the liquid phase and that, after a certain resting time (“aging time”), which depends on clay concentration, they exhibit the following physical states: i) phase separation in clay-poor phase and clay-rich phase, for cLAP ≤ 1%; ii) gel state, due to the attraction interactions between clay nanoplatelets, for 1% < cLAP < 2%; iii) repulsive glass state, where dominant are the repulsive interactions between clay particles, for 2% < cLAP < 3% [7]. A nematic gel is formed at LAP concentrations higher than 3%. The sol-gel transition depends on clay concentration, temperature and addition of salts or polymer [8–12].

3. LAPONITE® – BIOMEDICAL APPLICATIONS

LAP clay is a potential candidate for various applications in biomedical areas due to its unique properties: biocompatibility, high capacity to cationic exchange and ability to swell into water, its blood clotting ability promoting haemostasis. In the following, a brief review of the most important up-to-date biomedical applications of LAP-based materials is presented.

3.1. DRUG DELIVERY

Elaboration of systems able to control the drug release, in order to solve the medical problem for which they were designed, remains a major challenge for researchers in the biomedical field. Due to its structure, LAP can adsorb drugs within its interlayer spaces and release them under certain environmental conditions. The ability of LAP to adsorb/ desorb antibacterial molecules was used for designing materials for healthcare applications (for example, wound dressings, drug delivery systems, etc.).

New nanohydrogels based on sodium phosphate salts, polyacrylate and LAP, able to release individual drugs or mixtures of drugs, were developed by the inverse miniemulsion technique [13]. These nanohydrogels are uptaken by the cancer cells and, at pH value of 5.5, they swell and change their size from 100 nm to 1,500 nm, burst and disintegrate, releasing the antineoplastic drugs. It was proved that these


new hydrogels are biocompatible, biodegradable, non-cytotoxic and effective in killing HeLa and MCF-7 cancer cells.

Basu et al. designed a LAP/DNA hydrogel crosslinked with oxidized alginate, which had the capacity to function as a delivery vehicle for hydrophobic drugs (Fig. 2) [14].

Fig. 2. Preparation of LAP/DNA/alginate injectable hydrogel – adapted from [14].

The hydrogel is formed, on one hand, by crosslinking of DNA (with NH2 groups) and oxidized alginate (with CHO groups), leading to reversible imine linkages, and, on the other, by the electrostatic interactions between LAP nanoplatelets and the negatively charged DNA which give physical crosslink points.

Hydrogels suitable for applications in controlled drug delivery were obtained by physical crosslinking with LAP of a semi-interpenetrating network based on poly(vinyl alcohol) (PVA)/poly(N-isopropylacrylamide) [15]. The hydrogel containing 3% LAP and 1.5% PVA exhibited good mechanical properties, fast thermal response rate and good swelling capacity, being recommended for controlled drug release.

The effect of LAP nanoplatelets in the absence/ presence of antimicrobial peptide LL-37 (positively charged) on bacteria was investigated recently by Malekkhaiat Häffner et al. [16]. Peptide LL-37 binds to clay platelets surface developing a helix conformation favoured by the pH increase. Moreover, the pH increase determines the increase of the negative charge of nanoplatelets, favouring binding of the antimicrobial positively charged peptide LL-37. LAP nanoplatelets do not disrupt Escherichia coli bacteria (gram-negative), yet they cause the formation of bacterial flocculants. In the presence of LL-37, the bacterial membrane is disrupted, and bacterial aggregation occurs. No aggregation phenomena were observed in the presence of gram-positive bacteria (Bacillus subtilis). The ability of LAP nanoparticles to aggregate bacteria can be used as a strategy to limit the extension of infection and subsequent inflammation.

For encapsulation and release of proteins, injectable alginate hydrogels were obtained by a cryogelation process of alginates coupled to norbornene (Alg-N) or tetrazine (Alg-T), in the presence of LAP/protein mixture [17]. The protein was adsorbed onto LAP platelets incorporated in the alginate network (Fig. 3).


Fig. 3. Schematic representation of protein loading/release in LAP/alginate-based cryogels – adapted from [17].

The protein release profile can be tailored by adjusting clay concentration. The increase of LAP concentration in the initial clay/ protein mixture, subsequently used for alginate hydrogel preparation, determines increasing of nanoplatelets surface able to adsorb the proteins, hindering their release. Generally, most proteins do not interact with alginate chains, showing burst release kinetics from alginate hydrogel. Thereby, protein release kinetics can be tuned by finding the optimal clay/ alginate ratio.

Injectable heparin (with low molecular weight)/ Poloxamer 407/LAP hydrogels loaded with doxorubicin demonstrated very good in vitro and in vivo antitumor efficacy [18]. The presence of Poloxamer 407 confers to the hydrogel sensitivity to

temperature changes, showing sol-gel transition at 37C (Fig. 4). The positive doxorubicin molecules were adsorbed onto the negative surface of LAP platelets through an ion-exchange mechanism.

Fig. 4. Preparation of LAP/Heparin/Poloxamer 407 thermosensitive hydrogel – adapted from [18].


Nanosystems based on LAP were developed and loaded with two different anticancer drugs, i.e. methotrexate and doxorubicin. These drugs were then sequentially released and their release rate was accelerated under both extracellular acidity initiated by tumours and/ or by heating treatment [19].

3.2. WOUND DRESSINGS

Since prehistoric times, clays were used as natural remedies for skin wounds healing, soothing of irritations, stopping haemorrhages or skin cleaning. Clays are known as materials with anti-inflammatory, astringent and absorbent properties. Also, clays have been used in the treatment of malaria or stomach problems [20]. Considering the beneficial effect of clays on human health proven over time, scientists introduced clays as components in various pharmaceutical formulations or medical devices.

In recent years, the researches concerning the incorporation of LAP into (polymer-based) wound dressings have received more attention. Clay–antibacterial composites based on LAP and ciprofloxacin were developed and investigated as possible candidates for designing drug delivery systems [21]. LAP is able to adsorb almost instantly high concentrations of ciprofloxacin, preserving its activity against Staphylococcus epidermitis and Propionibacterium acnes. Thereby, nanohybrid hydrogels based on PVA and LAP were investigated as possible candidates for wound dressings. Cytocompatibility, hydrophilicity and mechanical properties of PVA are characteristics which make this polymer a promising choice in designing materials with biomedical applications (i.e., wound dressings, heart scaffolds, vascular networks) [22–24].

Golafshan et al. developed a new nanohybrid hydrogel based on LAP/PVA/alginate (PVA/alginate = 1/1) by incorporating LAP into the network formed by PVA and sodium alginate crosslinked covalently and ionically, respectively [25]. Optimal LAP concentration was established at 0.5%, when the hydrogel showed good swelling properties and reduced degradation ratio. Addition of LAP determined enhancement of the mechanical properties and blood coagulation activity.

Incorporation of LAP into rifampicin-loaded PVA, crosslinked by the freezing/ thawing procedure, increased the antibacterial activity against gram-negative (Escherichia coli) and gram-positive (Staphylococcus aureus) bacteria. The good mechanical properties, structural regeneration capacity after a high deformation of about 90%, water absorption capacity of 900% and their antibacterial activity make these hydrogels possible candidates for the design of wound healing dressings [26]. Glutaraldehyde-crosslinked PVA hydrogels (obtained for CHO/OH = 0.02), with 0.5% LAP, showed suitable properties (i.e., high elasticity and flexibility, good transparency, high surface roughness, high swelling degree) to be used for tailoring of wound dressings [27].

By the freeze-drying technique, chitosan (CS)/LAP nanocomposite scaffolds with properties necessary for their application in skin regeneration were obtained


by Gonzaga et al. [28]. The LAP presence in the scaffolds significantly improved the mechanical properties, cell adhesion, in vitro bioadhesive strength and porosity. It was established that 5% LAP is the optimal concentration in CS/LAP nanocomposite scaffolds to obtain the best structural and biological properties for application as wound dressing.

The gellan gum methacrylate/LAP hydrogels exhibited a lower swelling degree, due to the additional interactions between clay platelets and drug molecules (i.e., ofloxacin), which led to a slower drug diffusion rate than that of clay-free hydrogels. These biocompatible hydrogels could be used as support materials for wound dressings, being able to ensure healing of skin wounds caused by chronic infections [29].

Lokhande et al. reported the preparation of an injectable haemostat based on

kappa-carrageenan (-CA) by its physical and ionic crosslinking with LAP platelets and potassium chloride, respectively (Fig. 5) [30]

Fig. 5. Preparation of -CA/LAP nanocomposites with improved stability in physiological conditions – adapted from [30].

LAP platelets’ presence enhanced hydrogels stability in physiological conditions and accelerated twice the clotting time. These hybrid hydrogels could be used in designing of wound dressings for their high capacity to reduce haemorrhage and to heal wounds.

Hydrogels with properties suitable for biomedical applications in treating and healing wounds were designed by combining LAP with alginate and an antimicrobial


component (i.e., mafenide) [31]. Mafenide molecules are intercalated between clay platelets by a cation exchange mechanism which assumes replacement of Na

+

cations from LAP interlayers with the cationic drug. Release of Mg2+

cations from LAP structure was observed in simulated wound exudate fluid. The presence of Mg

2+ ions favours the wound healing process by increasing the cell growth rate,

and reduces the cytotoxicity of mafenide on fibroblast cells.

3.3. TISSUE ENGINEERING

LAP is a promising material which, alone or in combination with various polymers, is viable for tissue engineering applications. Its capacity to interact with protein and its osteogenesis properties are the main reasons for which scientists considered LAP a possible candidate for tailoring of biomaterials.

Adsorption of poly(ethylene oxide) (PEO) on the LAP platelets surface was intensively investigated, due to the unique physical properties which PEO/LAP dispersions exhibit (i.e., aging effect, shake-gel behaviour) [32–34].

An injectable hydrogel, containing a poly(ethylene glycol) (PEG)-based copolymer with imide blocks and LAP, with mechanical and structural properties suitable for articular cartilage, was obtained by Nojoomi et al. [35]. By addition of butane diamine (BDA) in a concentration below the toxic level, a crosslinked network was formed via an imide ring-opening mechanism. LAP presence in hydrogels slightly decreases the cell viability of scaffolds, while remaining higher than 80%, which indicates a reasonable biocompatibility. This cell viability diminution was attributed to the interactions between BDA molecules and clay platelets through ionic bonding. Injectable hydrogels with enhanced fibroblast cell adhesion, biocompatibility and biodegradability, applicable as articular cartilage scaffolds, were prepared by CS incorporation into PEG/LAP hydrogels [36]. Moreover, CS addition improves the viscoelastic properties of PEG/LAP hydrogels, due to the additional interactions established among the CS chains, CS-PEG and CS-clay [37]. LAP and CS favour the development of a mineralized extracellular matrix [38].

Recently, Zhang et al. reported the preparation of a supramolecular hydrogel based on guanidinylated CS and LAP for bone regeneration applications [39]. The supramolecular networks of these hydrogels are formed via salt-bridge by hydrogen bonds and electrostatic interactions between the guanidine ions from guanidinylated CS and oxyanions on LAP platelets surface. Hydrogels containing 3% LAP exhibited self-healing characteristics, injectable properties and high osteoinductivity.

An injectable system based on poly(ethylene glycol) diacrylate and LAP for tissue engineering was developed by Chang et al. [40]. These nanocomposite hydrogels showed enhanced mechanical properties, supported cell adhesion and spreading of stem cells on a 2D culture. For PEG/LAP systems, the clay and polymer concentrations, polymer molecular weight, temperature and resting time are important parameters for obtaining materials with the properties required for various medical applications [10,11].


Hydrogels, which can be used as synthetic matrices or scaffolds for tissue

engineering, were developed by Mignon et al. through UV-crosslinking of some

acrylate-endcapped urethane-based PEG precursors, in the presence of up to 1%

LAP [41]. The obtained materials showed a Young's modulus between 0.1 MPa

and 0.6 MPa, and an elasticity of about 95%. The materials containing 1% LAP and

synthetic polymers with PEG backbone of 2,000 g/mol promote cell attachment and

proliferation (up to 60%), being thus suitable for tissue regeneration applications.

Recently, Dong et al. developed artificial ligaments through incorporation of

LAP into regenerated silk fibroin [42]. Although LAP incorporation leads to a

slight decrease of the comprehensive mechanical properties, silk fibroin/LAP fibres

were better than those obtained from degummed natural silkworm silks and

regenerated silk fibroin.

Polycaprolactone/poly-DL-lactic acid/LAP (90/10/1) biodegradable composites

were investigated for designing an implantable device in the treatment of obesity

and type-2 diabetes [43]. Implantation of this device in rats determined the control

of body weight and blood glucose.

Scaffolds for bone tissue engineering were designed by addition of LAP and

of an antimicrobial peptide into poly(glycerol sebacate)-co-poly(ethylene glycol)

block copolymer [44]. Polycaprolactone was also included into scaffolds in order

to ensure the chain entanglements suitable for electrospinning process. LAP and

the antimicrobial peptide give to scaffolds osteoinductive and antimicrobial

properties, respectively. A slight decrease of mechanical properties was observed

by clay addition, yet the mechanical parameters remained in the range accepted in

bone tissue engineering. The activity and mineralization of alkaline phosphatase

(an indicator used in evaluation of osteoblastic differentiation and mineralization)

were enhanced through addition of LAP, which proves the possible use of these

scaffolds for bone tissue regeneration.

A recent investigation reported the possibility to prepare an injectable

hydrogel containing LAP for application in dentistry. Thereby, injectable hydrogel

microspheres (about 350 ~ 450 μm), based on arginine-glycine-aspartic acid (RGD)

conjugated to sodium alginate (RGD-alginate) and LAP, were developed by Zhang

et al. for endodontic regeneration [45]. The subcutaneous implantation in a mouse

model of tooth slices and RGD-alginate/0.5% LAP hydrogel microspheres, which

encapsulated human dental pulp stem cells and a vascular endothelial growth factor,

showed both pulp-like tissues regeneration and new micro-vessels formation within

1 month.

3.4. BIOSENSORS

Biosensor devices, which consist of bioreceptor, base material, transducer

and electronic system, are able to detect and convert the biochemical changes to a

signal which can be measured and analysed (Fig. 6).


Fig. 6. Schematic representation of a biosensor based on LAP – adapted from [46].

In latest years, hydrogel-based biosensors drew researchers attention due to

their enormous applicative potential in the biomedical field [46]. LAP, due to its

cation exchange ability, can function as a matrix for electroactive ion transfer. The

clay, deposited as a film onto the electrode surface, immobilizes the bioreceptors

(i.e., cell/ bacteria, redox proteins, DNA, antibody, etc.) by covalent bonds,

intercalation, physical adsorption, etc. The biological reaction between sample analyte

and immobilized bioreceptors is converted into a signal (i.e. electrochemical signal, pH,

heat, light, etc.) quantified and registered by the electronic system as an electric signal.

One of the first papers concerning the use of LAP in designing biosensors

refers to the development of an amperometric glucose biosensor [47]. Glucose

oxidase was incorporated into a LAP gel deposited onto platinum electrodes, after

which it was exposed to glutaraldehyde vapours in order to crosslink the enzymes.

The high stability over a long time (up to 100 days) and at temperatures up to 50C

demonstrated the possibility of using these biocomposite materials as biosensors.

A potential applicable biosensor with high sensitivity for testing of urea from

urine and blood was developed by immobilization of urease into LAP film through

crosslinking with glutaraldehyde [48]. The electrochemical properties of glucose

oxidase/LAP hydrogel film were improved by incorporation of thymine-based

polycations (vinylbenzyl thymine/vinylbenzyl triethylammonium chloride) [49].

By deposition of LAP/1-ethyl-3-methyl imidazolium chloride (ionic liquid) film on

indium-tin-oxide coated glass plates, an electrochemical biosensor for the

determination of ascorbic acid, cholesterol and oxalic acid was developed by Joshi

et al. [50].

Extensive descriptions of LAP-based biosensors can be found in the reviews

published by Mousty [51] and Tavakoli et al. [52].


3.5. RECENT MEDICAL TRENDS

Recently, the researchers investigated the possibility to use LAP

nanoplatelets for the elaboration of new materials efficient in cancer therapy and

diagnosis, having minimal side effects. In this regard, Wu et al. targeted the

incorporation of this nanoclay in a photoabsorbing agent for the development of a

material used in photothermal cancer therapies [53].

In latest years, a new method to design various structures for orthopaedic

applications has gained attention (e.g., the 3D technology) [54]. 3D bioprinting can

be used both in repair of organs or tissues with defects, and in the fabrication of

viable structures for transplants. 3D constructs mimic the native extracellular

matrix promoting regeneration of cell or tissues.

LAP is a versatile printing material which, in mixture with alginate, was used

in the preparation of soft materials with 3D architectures [55]. An optimal

LAP/alginate mixture was printed by 3D extrusion, after which the sample was

ionically or ionic-covalently crosslinked, to obtain single or double networks. The

single network (SN) was obtained by further immersing of LAP/alginate sample into a

0.1 M CaCl2 aqueous solution. The double network was realized by immersion of

SN gel into an acrylamide (as monomer)/N,N’-methylenebisacrylamide (as

crosslinker)/2-hydroxy-4’-(2-hydroxyethoxy)-2-methylpropiophenone (as photoinitiator)

mixture, followed by its UV crosslinking.

Mixtures of LAP with alginate and methylcellulose were used to build

scaffolds for tissue engineering applications [56]. LAP presence increased the

printability and shape fidelity, and it was beneficial for the controlled release of the

biologically active compounds.

Recently, Dening et al. reported the possibility to use spray-dried LAP

particles as a novel anti-obesity treatment, as a result of the high adsorptive

capacity of smectite clays [57]. It was proved that LAP particles adsorb dietary

lipids and reduce weight gain, with few adverse effects.

The hydrophobicity and potential of the sorbent/ sorbate surfaces determine

the adsorption capacity of bacteriophages to clays [58]. Most investigations on

adsorption of viruses on clay nanoplatelets were made on nonenveloped viruses,

although many viruses in the environment are enveloped (for example,

coronavirus). Thereby, Block et al. studied the interactions between smectite clay

and bacteriophage cystoviridae species φ6 used as a model for enveloped human

viruses [59]. In the presence of smectite clay, the virions are caught between the

clay platelet layers or are attached on platelets edges. Further, the virions swell and

disassemble, leading to the partial or total loss of their envelope, which suggests

that smectite clay could reduce infectivity.


4. CONCLUSIONS AND PERSPECTIVES

LAP represents a promising nanomaterial due to its exceptional properties,

such as biocompatibility, ability to form gels by physical crosslinking, high surface

area and high capacity to cationic exchange. Moreover, non-toxicity of the

compounds resulted after its degradation in physiological pH condition and its

osteoinductive properties have attracted the attention of researchers interested in

the elaboration of biomedical materials or devices.

The ability of LAP nanoplatelets to interact with various molecule types

offers new perspectives in drug delivery/ wound healing applications. From this

perspective, researchers are interested in formulation of new LAP-based support

materials which can ensure a high stability of the product and a well-controlled

release of drug.

Knowing the capacity of this nanoclay to interact with various enzymes, the

design of new stable hydrogel-based biosensors, which can be used in the first

diagnosis stage, for the identification of small molecules (i.e., cholesterol, glucose,

urea) represents an open challenge for researchers.

Incorporation of LAP (found to have bioactive and osteoinductive properties)

into different synthetic materials remains an interesting path in designing of new

nanocomposites for tissue engineering and regenerative medicine. Designing

advanced biological systems for various biomedical applications by applying 4D

printing technology represents a new perspective for the development of scaffolds,

bioactuators, biorobots or other smart medical devices [60,61].

In the context of the current global pandemic, LAP could be considered for

the development of biomedical systems used both in prevention and healing of

COVID-19 infection, due to its high microorganisms absorption properties [62].

LAP remains a nanomaterial of interest for developing new medical

materials/ devices applicable in the top fields of modern medicine.

R E F E R E N C E S

1. GAHARWAR A.K., CROSS L.M., PEAK C.W., GOLD K., CARROW J.K., BROKESH A.,

SINGH, K.A., 2D Nanoclay for biomedical applications: Regenerative medicine, therapeutic

delivery, and additive manufacturing, Adv. Mater., 2019, 31, (23), 1900332-1–28.

2. TOMÁS H., ALVES C.S., RODRIGUES J., Laponite®: A key nanoplatform for biomedical

applications?, Nanomedicine, 2018, 14, (7), 2407–2420.

3. KROON M., WEGDAM G.H., SPRIK R., Dynamic light scattering studies on the sol-gel

transition of a suspension of anisotropic colloidal particles, Phys. Rev. E., 1996, 54, (6), 6541–

6550 (1996).

4. AVERY R.G., RAMSAY J.D.F., Colloidal properties of synthetic hectorite clay dispersions. II.

Light and small angle neutron scattering, J. Colloid Interface Sci., 1986, 109, (2), 448–454.

5. LI L., HARNAU, L., ROSENFELDT S., BALLAUFF M., Effective interaction of charged

platelets in aqueous solution: Investigations of colloid laponite suspensions by static light

scattering and small-angle X-ray scattering, Phys. Rev. E., 2005, 72, (5), 051504-1–10.


6. THOMPSON D.W., BUTTERWORTH J.T., The nature of laponite and its aqueous dispersions, J.

Colloid Interface Sci., 1992, 151, (1), 236–243. 7. RUZICKA B., ZACCARELLI E., A fresh look at the Laponite phase diagram, Soft Matter, 2011,

7, (4), 1268–1286. 8. LABANDA J., LLORENS J., Rheology of laponite colloidal dispersions modified by sodium

polyacrylates, Colloids Surf., A., 2004, 249, (1–3), 127–129. 9. MONGONDRY P., NICOLAI T., TASSIN J.-F., Influence of pyrophosphate or polyethylene

oxide on the aggregation and gelation of aqueous laponite dispersions, J. Colloid Interface Sci.,

2004, 275, (1), 191–196.

10. MORARIU S., BERCEA M., Effect of addition of polymer on the rheology and electrokinetic features of Laponite RD aqueous dispersions, J. Chem. Eng. Data, 2009, 54, (1), 54–59.

11. MORARIU S., BERCEA M., Effect of temperature and aging time on the rheological behavior of

aqueous poly(ethylene glycol)/Laponite RD dispersions, J. Phys. Chem. B, 2012, 116, (1), 48–54. 12. BAILEY L., LEKKERKERKER H.N.W., MAITLAND G.C., Smectite clay – inorganic

nanoparticle mixed suspensions: phase behaviour and rheology, Soft Matter, 2015, 11, (2), 222–236. 13. BECHER T.B., MENDONÇA M.C.P., DE FARIAS M.A., PORTUGAL R.V., DE JESUS M.B.,

ORNELAS C., Soft nanohydrogels based on laponite nanodiscs: A versatile drug delivery platform for theranostics and drug cocktails, ACS Appl. Mater. Interfaces, 2018, 10, (26), 21891–21900.

14. BASU S., PACELLI S., PAUL A., Self-healing DNA-based injectable hydrogels with reversible covalent linkages for controlled drug delivery, Acta Biomater., 2020, 105, 159–169.

15. DJONLAGIC J., LANCUSKI A., NIKOLIC M.S., ROGAN J., OSTOJIC S., PETROVIC Z., Hydrogels reinforced with nanoclays with improved response rate, J. Appl. Polym. Sci., 2017,

134, (9), 44535-1–14. 16. MALEKKHAIAT HÄFFNER S., NYSTRÖM L., BROWNING K.L., MÖRCK NIELSEN H.,

STRÖMSTEDT A.A., VAN DER PLAS M.J.A., SCHMIDTCHEN A., MALMSTEN M., Interaction of laponite with membrane components—consequences for bacterial aggregation and

infection confinement, ACS Appl. Mater. Interfaces, 2019, 11, (17), 15389–15400. 17. KOSHY S.T., ZHANG D.K.Y., GROLMAN J.M., STAFFORD A.G., MOONEY D.J., Injectable

nanocomposite cryogels for versatile protein drug delivery, Acta Biomater., 2018, 65, 36–43. 18. LI J., PAN H., QIAO S., LI Y., WANG J., LIU W., PAN W., The utilization of low molecular

weight heparin-poloxamer associated laponite nanoplatform for safe and efficient tumor therapy,

Int. J. Biol. Macromol., 2019, 134, 63–72. 19. ZHENG L., ZHOU B., QIU X., XU X., LI G., LEE W.Y.W., JIANG J., LI Y., Direct assembly of

anticancer drugs to form laponite-based nanocomplexes for therapeutic co-delivery, Mater. Sci. Eng. C, 2019, 99, 1407–1414.

20. CARRETERO M.I., GOMES C.S.F., TATEO F., Clays and Human Health, Eds. Bergaya F., Theng B.K.G., Lagaly G., Developments in Clay Science, pp. 717–741, Elsevier (2006)

21. HAMILTON A.R., HUTCHEON G.A., ROBERTS M., GASKELL E.E., Formulation and antibacterial profiles of clay–ciprofloxacin composites, Appl. Clay Sci., 2014, 87, 129–135.

22. MORARIU S., BERCEA M., TEODORESCU M., AVADANEI M., Tailoring the properties of poly(vinyl alcohol)/poly(vinylpyrrolidone) hydrogels for biomedical applications, Eur. Polym. J.,

2016, 84, 313–325. 23. TEODORESCU M., BERCEA M., MORARIU S., Biomaterials of poly(vinyl alcohol) and

natural polymers, Polym. Rev., 2018, 58, (2), 247–287. 24. TEODORESCU M., BERCEA M., MORARIU S., Biomaterials of PVA and PVP in medical and

pharmaceutical applications: Perspectives and challenges, Biotechnol. Adv., 2019, 37, (1), 109–131. 25. GOLAFSHAN N., REZAHASANI R., TARKESH ESFAHANI M., KHARAZIHA M.,

KHORASANI S.N., Nanohybrid hydrogels of laponite: PVA-Alginate as a potential wound healing material, Carbohydr. Polym., 2017, 176, 392–401.

26. MORARIU S., BERCEA M., GRADINARU L.M., ROSCA I., AVADANEI M., Versatile poly(vinyl alcohol)/clay physical hydrogels with tailorable structure as potential candidates for

wound healing applications, Mater. Sci. Eng. C, 2020, 109, 110395-1–11.


27. MORARIU S., BERCEA M., BRUNCHI C.-E., Influence of Laponite RD on the properties of poly(vinyl alcohol) hydrogels, J. Appl. Polym. Sci., 2018, 135, (35), 46661-1–11.

28. GONZAGA V.A.M., POLI A.L., GABRIEL J.S., TEZUKA D.Y., VALDES T.A., LEITÃO A., RODERO C.F., BAUAB T.M., CHORILLI M., SCHMITT C.C., Chitosan-laponite nanocomposite scaffolds for wound dressing application, J. Biomed. Mater. Res. B, 2020, 108, (4), 1388–1397.

29. PACELLI S., PAOLICELLI P., MORETTI G., PETRALITO S., DI GIACOMO S., VITALONE A., CASADEI M.A., Gellan gum methacrylate and laponite as an innovative nanocomposite hydrogel for biomedical applications, Eur. Polym. J., 2016, 77, 114–123.

30. LOKHANDE G., CARROW J.K., THAKUR T., XAVIER J.R., PARANI M., BAYLESS K.J., GAHARWAR A.K., Nanoengineered injectable hydrogels for wound healing application, Acta Biomater., 2018, 70, 35–47.

31. GHADIRI M., CHRZANOWSKI W., ROHANIZADEH R., Antibiotic eluting clay mineral (Laponite®) for wound healing application: an in vitro study, J. Mater. Sci. Mater. Med., 2014, 25, (11), 2513–2526.

32. KISHORE S., CHEN Y., RAVINDRA P., BHATIA S.R., The effect of particle-scale dynamics on the macroscopic properties of disk-shaped colloid–polymer systems, Colloids Surf., A., 2015, 482, 585–595.

33. MORARIU S., BERCEA M., Viscoelastic properties of Laponite RD dispersions containing PEO with different molecular weights, Rev. Roum. Chim., 2015, 60, (7-8), 777–785.

34. ZHENG B., BRETON J.R., PATEL R.S., BHATIA S.R., Microstructure, microrheology, and dynamics of laponite® and laponite®-poly(ethylene oxide) glasses and dispersions, Rheol. Acta, 2020, 59, (4), 387–397.

35. NOJOOMI A., TAMJID E., SIMCHI A., BONAKDAR S., STROEVE P., Injectable polyethylene glycol-laponite composite hydrogels as articular cartilage scaffolds with superior mechanical and rheological properties, Int. J. Polym. Mater., 2017, 66, (3), 105–114.

36. JIN Q., SCHEXNAILDER P., GAHARWAR A.K., SCHMIDT G., Silicate cross-linked bio-nanocomposite hydrogels from PEO and chitosan, Macromol. Biosci., 2009, 9, (10), 1028–1035.

37. MORARIU S., BERCEA M., SACARESCU L., Tailoring of clay/poly(ethylene oxide) hydrogel properties by chitosan incorporation, Ind. Eng. Chem. Res., 2014, 53, (35), 13690–13698.

38. GAHARWAR A.K., SCHEXNAILDER P.J., JIN Q., WU C.-J., SCHMIDT G., Addition of chitosan to silicate cross-linked PEO for tuning osteoblast cell adhesion and mineralization, ACS Appl. Mater. Interfaces, 2010, 2, (11), 3119–3127.

39. ZHANG X., FAN J., LEE C.-S., KIM S., CHEN C., LEE M., Supramolecular hydrogels based on nanoclay and guanidine-rich chitosan: Injectable and moldable osteoinductive carriers, ACS Appl. Mater. Interfaces, 2020, 12, (14), 16088–16096.

40. CHANG C.-W., VAN SPREEUWEL A., ZHANG C., VARGHESE S., PEG/clay nanocomposite hydrogel: a mechanically robust tissue engineering scaffold, Soft Matter, 2010, 6, (20), 5157–5164.

41. MIGNON A., PEZZOLI D., PROUVÉ E., LÉVESQUE L., ARSLAN A., PIEN N., SCHAUBROECK D., VAN HOORICK J., MANTOVANI D., VAN VLIERBERGHE S.,

DUBRUEL P., Combined effect of laponite and polymer molecular weight on the cell-interactive properties of synthetic PEO-based hydrogels, Reac. Funct. Polym., 2019, 136, 95–106.

42. DONG Q., CAI J., WANG H., CHEN S., LIU Y., YAO J., SHAO Z., CHEN X., Artificial ligament made from silk protein/laponite hybrid fibers, Acta Biomater., 2020, 106, 102–113.

43. HSU W.-H., CHANG H.-M., LEE Y.-L., PRASANNAN A., HU C.-C., WANG J.-S., LAI J.-Y., YANG J.M., JEBARANJITHAM N., TSAI H.-C., Biodegradable polymer-nanoclay composites as intestinal sleeve implants installed in digestive tract for obesity and type 2 diabetes treatment, Mater. Sci. Eng. C, 2020, 110, 110676-1–7.

44. IBRAHIM D.M., SANI E.S., SOLIMAN, A.M., ZANDI N., MOSTAFAVI E., YOUSSEF A.M., ALLAM N.K., ANNABI N., Bioactive and elastic nanocomposites with antimicrobial properties for bone tissue regeneration, ACS Appl. Bio Mater., 2020, 3, (5), 3313–3325.

45. ZHANG R., XIE L., WU H., YANG T., ZHANG Q., TIAN Y., LIU Y., HAN X., GUO W., HE

M., LIU S., TIAN W., Alginate/laponite hydrogel microspheres co-encapsulating dental pulp

stem cells and VEGF for endodontic regeneration, Acta Biomater., 2020, 113, 305–316.


46. GHADIRI M., CHRZANOWSKI W., ROHANIZADEH R., Biomedical applications of cationic

clay minerals, RSC Adv., 2015, 5, (37), 29467–29481.

47. POYARD S., JAFFREZIC-RENAULT N., MARTELET C., COSNIER S., LABBE P.,

BESOMBES J.L., A new method for the controlled immobilization of enzyme in inorganic gels

(laponite) for amperometric glucose biosensing, Sens. Actuators B Chem., 1996, 33, (1-3), 44–49.

48. de MELO J.V., COSNIER S., MOUSTY C., MARTELET C., JAFFREZIC-RENAULT N., Urea

biosensors based on immobilization of urease into two oppositely charged clays (laponite and

Zn−Al layered double hydroxides), Anal. Chem., 2002, 74, (16), 4037–4043.

49. PAZ ZANINI V.I., GAVILÁN M., LÓPEZ de MISHIMA B.A., MARTINO D.M.,

BORSARELLI C.D., A highly sensitive and stable glucose biosensor using thymine-based

polycations into laponite hydrogel films, Talanta, 2016, 150, 646–654.

50. JOSHI N., RAWAT K., SOLANKI P.R., BOHIDAR H.B., Biocompatible laponite ionogels

based non-enzymatic oxalic acid sensor, Sens. Biosensing Res., 2015, 5, 105–111.

51. MOUSTY C., Biosensing applications of clay-modified electrodes: A review, Anal. Bioanal.

Chem., 2010, 396, 315–325.

52. TAVAKOLI J., TANG Y., Hydrogel based sensors for biomedical applications: An updated

review, Polymers, 2017, 9, (8), 364-1–25.

53. WU H., WANG W., ZHANG Z., LI J., ZHAO J., LIU Y., WU C., HUANG M., LI Y., WANG S.,

Synthesis of a clay-based nanoagent for photonanomedicine, ACS Appl. Mater. Interfaces, 2020,

12, (1), 390–399.

54. AFEWERKI S., MAGALHÃES L.S.S.M., SILVA A.D.R., STOCCO T.D., SILVA FILHO E.C.,

MARCIANO F.R., LOBO A.O., Bioprinting a synthetic smectic clay for orthopedic applications,

Adv. Healthcare Mater., 2019, 8, (13), 1900158-1–14.

55. DÁVILA J.L., d’ÁVILA M.A., Rheological evaluation of laponite/alginate inks for 3D extrusion-

based printing, Int. J. Adv. Manuf. Technol., 2019, 101, (1-4), 675–686.

56. AHLFELD T., CIDONIO G., KILIAN D., DUIN S., AKKINENI A.R., DAWSON J.I., YANG S.,

LODE A., OREFFO R.O.C., GELINSKY M., Development of a clay based bioink for 3D cell

printing for skeletal application, Biofabrication, 2017, 9, (3), 034103-1–16.

57. DENING T.J., JOYCE P., KOVALAINEN M., ULMEFORS GUSTAFSSON H., PRESTIDGE

C., Spray dried smectite clay particles as a novel treatment against obesity, Pharm. Res., 2018, 36,

(1), 21-1–14.

58. CHATTOPADHYAY S., PULS R.W., Adsorption of bacteriophages on clay minerals, Environ.

Sci. Technol., 1999, 33, (20), 3609–3614.

59. BLOCK K.A., TRUSIAK A., KATZ A., GOTTLIEB P., ALIMOVA A., WEI H., MORALES J.,

RICE W.J., STEINER J.C., Disassembly of the cystovirus ϕ6 envelope by montmorillonite clay,

Microbiologyopen, 2014, 3, (1), 42–51.

60. GUO J., ZHANG R., ZHANG L., CAO X., 4D Printing of robust hydrogels consisted of agarose

nanofibers and polyacrylamide, ACS Macro Lett., 2018, 7, (4), 442–446.

61. ZHU W., WEBSTER T.J., ZHANG L.G., 4D printing smart biosystems for nanomedicine,

Nanomedicine (Lond.), 2019, 14, (13), 1643–1645.

62. MISHRA B.B., ROY R., SINGH S.K., SHARMA S.K., PRASAD B.D., JHA A.K., SAHNI S.,

Preventive measures against transmission and multiplication of COVID-19 following the simple

natural laws with soil, clay, and biodiversity, Open Access Journal of Environmental and Soil

Sciences (OAJESS), 2020, 5, (2), 622–632.

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LAPONITE A VERSATILE COMPONENT IN HYBRID MATERIALS …