Category: Health Industry

Graphene and nanomedicine: the perfect combination for improved health

Posted on | by Energeia Graphenemex

Graphene and nanomedicine:

the perfect combination for improved health

Part III. Dentistry- Implantology

The application of nanotechnology in nanomedicine is based on the fact that most biological molecules, from DNA, amino acids and proteins to constituents such as hydroxyapatite and collagen fibrils, among others, exist and function at the nanometric scale.

Nanometer (nm): millionth of 1 millimeter.

Graphene materials are two-dimensional (2D) sheet-shaped carbon nanoparticles that have gained popularity in the field of biomedical sciences not only for their incredible mechanical, thermal, electrical, optical, and biological properties, but also for their ability to transfer these properties to other materials allowing the possibility of creating new compounds with advanced characteristics. In Odontology, and particularly in relation to implantology, this transfer of properties has opened numerous lines of research with great expectations due to the interesting synergistic effect between infection control and its regenerative capacity.1

Nanoparticle: particle that measures between 1 and 100 nm.

Graphene as a new strategy for the design and manipulation of dental implants and tissue regeneration. Taken from Tissue Eng Regen Med. 2017; 14(5):481

What are the problems that graphene could solve?

Osseointegration

One of the main concerns after the placement of an implant is the failure of its osseointegration. This can occur because instead of bone cells growing at the bone-implant interface, fibrous tissue grows that does not allow implant stabilization. An alternative to favor site conditions where cell interactions will occur is modification of the implant surface by physical or chemical methods to create nanoporosities that increase surface area and favor cell activity. 2

Osseointegration: Firm, stable, and long-lasting connection between an implant and the surrounding bone. Its success depends on biological and systemic factors of the patient, in addition to the characteristics of the implant.

In the case of graphene materials, in addition to their extensive and extremely thin surface area one atom thick, another of their added values is the cloud of electrons that surrounds them, and the presence of some oxygenated groups allows them to interact with proteins serum to form a focal adhesion. In other words, the hydrophobic/hydrophilic nature of these nanomaterials in combination with the roughness of the surface contributes to the interaction with proteins and later with cells, acting as a scaffold to promote the growth, differentiation, and anchorage of bone cells in the implant, paving the way for a stable and predictable osseointegration with a better projection of useful life.3,4

The regenerative impact of graphene materials lies in their great ability to adsorb proteins, creating a layer between cells and the surfaces of the materials to promote cell adhesion and proliferation.1

Infection control

Another cause for implant failure is the appearance of peri-prosthetic or peri-implant infections; to avoid them, it is common to use techniques such as antibiotic impregnation, local drug delivery systems, and the coating of implants with titanium nanotubes, silver nanoparticles, or polypeptide nanofilms for the controlled release of antibiotics.5 However, the worrying increase of antibiotic resistance has made these strategies less and less effective.

Graphene materials, in addition to their biocompatibility, have intrinsic antimicrobial properties with advantages over traditional antibiotics as they have less chance of developing microbial resistance. Odontology has been exploring these effects for several years on bioceramic materials such as alumina and zirconium, metals such as titanium, restorative materials such as glass ionomer, and polymeric materials such as polymethyl methacrylate (PMMA), to name a few. In general, the antimicrobial mechanisms accepted for these nanostructures are: 1) physical damage to the membrane, 2) oxidative stress, 3) inactivation by electron withdrawal, 4) isolation against the passage of nutrients and finally, 5) in the case of coatings, control of hydrophobicity and surface energy can also prevent cell attachment with low affinity and prevent biofilm formation.6,7

Biofilm: Layer of microorganisms that grow and adhere to the surface of a natural structure such as teeth (dental plaque) or artificial such as a medical device (intravascular catheters).

In 2021, a group of scientists from the University of Gwangju, Korea, published a study in which they coated zirconium implants with graphene oxide using the argon plasma method. Their results reported that this modification reduced by 58.5% the presence of Streptococcus mutans, the bacterium with the greatest influence on the formation of dental plaque and dental caries, agreeing with a significant reduction in biofilm thickness of 43.4%. In addition to the antimicrobial effect, they also showed a statistically significant increase of 3.2% and 15.7% in the proliferation and differentiation of bone cells.8 These results are consistent with what was reported by the Jiao Tong University, Shanghai, on a hybrid material of titanium with graphene. synthesized by the spark plasma sintering (SPS) technique. Similarly, the research demonstrated an interesting decrease in the formation of multibacterial biofilms composed of Streptococcus mutans, Fusobacterium nucleatum and Porphyromonas gingivalis, accompanied by an improvement in the activity of human gingival fibroblasts, one of the most important cell groups involved in healing.9 In addition to the synergy between infection control and its regenerative capacity, other studies related to dental implantology are also focusing their attention on the mechanical properties for the design of new implants or restorative materials. 10-12

Energeia-Graphenemex, the pioneering Mexican company in Latin America in the research and development of applications with graphene materials, throughout its 10-year career has overcome numerous scientific and commercial challenges to reach the market with products for different industries. And being aware that to reach the health sector it is essential to carry out exhaustive evaluations, kindly invites all those companies and/or research centers that are interested in continuing to explore the benefits of graphene materials and laying increasingly solid foundations on their safe use for biomedical applications.

Drafting: EF/DHS

References

  1. ¿Can Graphene Oxide Help to Prevent Peri-Implantitis in the Case of Metallic Implants? Coatings 2022, 12, 1202.
  2. New design of a cementless glenoid component in unconstrained shoulder arthroplasty: a prospective medium term analysis of 143 cases. Eur J Orthop Surg Traumatol 2013. 23(1):27–34 7.
  3.  European Journal of Orthopaedic Surgery & Traumatology (2018) 28:1257
  4. Graphene-Based Biomaterials for Bone Regenerative Engineering: A Comprehensive Review of the Field and Considerations Regarding Biocompatibility and Biodegradation. Adv. Healthc. Mater. 2021, 2001414.
  5. Nanotechnology and bone regeneration: a mini review. 2014 Int Orthop 38(9):1877–1884 /1. European Journal of Orthopaedic Surgery & Traumatology (2018) 28:1257
  6. Graphene: ¿An Antibacterial Agent or a Promoter of Bacterial Proliferation? iSciencie. 2020.  23, 101787
  7. Graphene: The game changer in dentistry. IP Annals of Prosthodontics and Restorative Dentistry 2022;8(1):10
  8. Antibacterial Activity of Graphene Depends on Its Surface Oxygen Content.
  9. Direct-Deposited Graphene Oxide on Dental Implants for Antimicrobial Activities and OsteogenesisInt. J. Nanomedicine 2021 :16 5745
  10. Graphene-Reinforced Titanium Enhances Soft Tissue Seal. Front. Bioeng. Biotechnol. 2021. 9:665305.
  11. Graphene-Doped Polymethyl Methacrylate (PMMA) as a New Restorative Material in Implant-Prosthetics: In Vitro Analysis of Resistance to Mechanical Fatigue. J. Clin. Med. 2023, 12, 1269.
  12. Mechanical Characterization of Dental Prostheses Manufactured with PMMA–Graphene Composites. Materials 2022, 15, 5391
  13. Fabrication and properties of in situ reduced graphene oxide-toughened zirconia composite ceramics. J. Am. Ceram. Soc. 2018, 101, 8

The safety of graphene in human health: what science says about it

Posted on | by Energeia Graphenemex

The safety of graphene in human health:

what science says about it

Part II. Are graphene materials safe for humans?

The family of graphene materials comprises a wide range of two-dimensional (2D) carbon nanostructures in the form of sheets that differ from each other by the particularities derived from the production method or by the innumerable functionalizations that can be performed after its obtaining. In 2022, Nature magazine, one of the most important scientific journals in the world, published a study in which 36 products from graphene suppliers from countries such as the United States, Norway, Italy, Canada, India, China, Malaysia and England were analyzed, concluding that graphenes represent a heterogeneous class of materials with variable characteristics and properties, whether mechanical, thermal, electrical, optical, biological, etc., which can be transferred to a large number of three-dimensional (3D) compounds to modify or create new products.

“Undoubtedly, graphene and nanotechnology in general continue to be controversial issues as they confront us with a world that is difficult to see and understand, but with simply amazing effects”

Are graphene materials safe?

Graphene materials promise to be an important tool within biomedical technologies. In principle, its benefits can be used for the design of diagnostic elements such as sensors and devices for images up to neural interfaces, gene therapy, drug delivery, tissue engineering, infection control, phototherapy for cancer treatment, bioelectronic and dental medicine, among other. But for them to be truly used in this type of technology, their interactions with the biological environment must first be understood or, failing that, ensure that their presence does not alter the natural environment of the cells. In this sense, numerous studies have been carried out with the different forms, presentations, and available concentrations of graphene whose findings have gradually paved the way for its safe use in biomedical technologies:

i) Graphene materials in their free form. In in vitro tests, exposure of human lung epithelial cells to graphene sheets at concentrations lower than 0.005 mg/ml did not cause significant changes in their morphology or adhesion,2,3 nor was cytotoxic activity identified in stem cells derived from adipose tissue. human, periodontal ligament and dental pulp exposed to 0.5 mg/ml of GO,4 even and understanding a possible dose-size dependent effect, other investigations report safe concentrations below 40 mg/ml or, that do not exceed 1, 5% w/v. 5-8

Finally, one of the most recent in vivo studies published by the University of Manchester, United Kingdom, on the pulmonary response of mice exposed to graphene oxide (GO) in the respiratory tract, did not identify significant damage or pulmonary fibrosis at 90-day follow-up. These results provide solid grounds for the safety of these nanostructures without underestimating basic safety measures, such as avoiding their inhalation.9 Likewise, scientists from the University of Trieste, Italy, analyzed the impact of graphene materials on the skin, reporting low toxicity on cells.10

“It is unlikely that graphene materials in their free form are used to be in contact with the biological environment, they are generally functionalized or immobilized in other materials to develop an application”

ii) Functionalized graphene materials. Functionalization is the term that refers to the chemical modification of a nanomaterial to give it a “function”, that is, to facilitate its incorporation with other compounds or to benefit its biocompatibility and better direct its use by anchoring functional groups, molecules, or nanoparticles. A study published in the journal Nature Communications on graphene bioapplications highlights the importance of its functionalization with amino groups to make it more compatible with human immune cells.11,12

“The most common functionalization of graphene is the anchoring of oxygenated groups on its surface, this material is known as graphene oxide”

iii) Immobilization in polymers. The use of graphene materials as nano-filling for plastics, resins, coatings, etc., is the most common way in which these nanostructures are used. For the biomedical sector, its immobilization in polymers has shown good biocompatibility and stimulation of cell proliferation; antimicrobial activity and improvement of the mechanical properties of polymers, being classified as excellent candidates for the manufacture of bone fixation devices, molecular scaffolds, orthopedic implants, or dental materials.13-15

Given the great potential of graphene materials in health sciences, but also due to the many questions about their safety, an international research team from the European Graphene Flagship project, led by EMPA (German acronym for the Federal Institute for Testing and Materials Research), conducted a study to assess the potential health effects of graphene materials immobilized within a polymer; the results showed that the graphene particles released from said polymeric compounds after abrasion induce insignificant effects.16

“It is reassuring to see that this study shows negligible effects, confirming the viability of graphene for mass applications. Andrea C. Ferrari, Graphene Flagship Science and Technology Officer.” 17,18

Energeia-Graphenemex, the pioneering Mexican company in Latin America in the research and development of applications with graphene materials, throughout its 10-year career has overcome numerous scientific and industrial challenges to reach the market with products for industrial use. In 2018, it began to explore the antimicrobial capabilities of its products with excellent results in vitro and in a relevant environment; currently, and in conjunction with other research centers, it is carrying out evaluations to explore the potential of its materials as nano-reinforcement of biopolymers.

Drafting: EF/DHS

References

  1. Cytotoxicity survey of commercial graphene materials from worldwide. npj 2D Materials and Applications (2022) 6:65
  2. Biocompatibility of Pristine Graphene Monolayers, Nanosheets and Thin Films. 2014, 1406.2497.
  3. Preliminary In Vitro Cytotoxicity, Mutagenicity and Antitumoral Activity Evaluation of Graphene Flake and Aqueous Graphene Paste. Life 2022, 12, 242
  4. Biological and physico-mechanical properties of poly (methyl methacrylate) enriched with graphene oxide as a potential biomaterial. J Oral Res 2021; 10(2):1
  5.  Graphene substrates promote adherence of human osteoblasts and mesenchymal stromal cells. Carbon. 2010; 48: 4323–9
  6. Multi-layer Graphene oxide in human keratinocytes: time-dependent cytotoxicity. Prolifer Gene Express Coat 2021; 11:1
  7. Cytotoxicity assessment of graphene-based nanomaterials on human dental follicle stem cells. Colloids Surf B Biointerfaces. 2015; 136:791
  8. Arabinoxylan/graphene-oxide/nHAp-NPs/PVA bionano composite scaffolds for fractured bone healing. 2021. J. Tissue Eng. Regen. Med. 15, 322.
  9. Size-Dependent Pulmonary Impact of Thin Graphene Oxide Sheets in Mice: Toward Safe-by-Design. Adv. Sci. 2020, 7, 1903200
  10. Differential cytotoxic effects of graphene and graphene oxide on skin keratinocytes. 2017. Sci Rep 7, 40572
  11. Amine-Modified Graphene: Thrombo-Protective Safer Alternative to Graphene Oxide for Biomedical Applications. ACS Nano 2012, 6, 2731
  12. Single-cell mass cytometry and transcriptome profiling reveal the impact of graphene on human immune cells. Nature Communications, 2017, 8: 1109,
  13. In-vitro cytotoxicity of zinc oxide, graphene oxide, and calcium carbonate nano particulates reinforced high-density polyethylene composite. J. Mater Res. Technol. 2022. 18: 921
  14. Graphene-Doped Polymethyl Methacrylate (PMMA) as a New Restorative Material in Implant-Prosthetics: In Vitro Analysis of Resistance to Mechanical FatigueJ. Clin. Med. 2023, 12, 1269
  15. High performance of polysulfone/ Graphene oxide- silver nanocomposites with excellent antibacterial capability for medical applications. Matter today commun. 2021. 27
  16. Hazard assessment of abraded thermoplastic composites reinforced with reduced graphene oxide. J. Hazard Mater. 2022. 435. 129053
  17. https://www.empa.ch/web/s604/graphene-dust
  18. https://www.graphene-info.com/researchers-asses-health-hazards-graphene-enhanced-composites

Graphene: The next revolution in biomedical applications

Posted on | by Energeia Graphenemex

Graphene:

The next revolution in biomedical applications

Part I. Tissue Engineering

Advances in medicine have reached levels unimagined until recently. Among them, tissue engineering has an important participation. With it is possible to combine cells, biomaterials and biologically active molecules with the aim of repairing or replicating tissues or organs with a function similar to that of the original structure. In principle, biomaterials are used as molecular scaffolds to act as a three-dimensional (3D) support or guide for the anchoring and growth of the cells that will be in charge of forming the new tissue.

The first molecular scaffolds were designed with natural materials such as collagen, glycosaminoglycans (GAGs), chitosan, and alginates; then with artificial compounds such as polylactic acid (PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic) acid (PLGA), polyurethanes (PUs), polytetrafluoroethylene (PTFE), polyethyleneterephthalate (PET); bioceramics such as hydroxyapatite (HA) and tricalcium phosphate; metals such as stainless steel, chrome-cobalt alloys (Co-Cr) or titanium alloys (Ti) and recently, new research is oriented towards the use of nanotechnology.

The relationship between nanotechnology and tissue engineering is due to the fact, that the extracellular matrix (ECM) that helps cells unite and communicate with each other, is made up of a network of nanometer-sized fibers made up of bioactive molecules. It is at this point where nanotechnology opens new possibilities for regenerative medicine, since it has been proven that the use of materials that act on the same nanometric scale as the ECM favors mimicking the physiological environment of the organism to stimulate cell growth and differentiation in a more natural environment.

Among the most studied nanomaterials in recent years are graphene materials, which consist of nanometric sheets of carbon atoms organized in two-dimensional (2D) hexagonal networks. Among the most interesting properties for tissue engineering are: its large surface area, mechanical resistance, thermal conductivity, biocompatibility and finally, an extraordinary ability to share its properties with other materials to improve their original characteristics.

For example, the use of graphene materials within the 3D architecture of certain biopolymers in tests carried out on heart, liver, bone, cartilage, and skin tissues has shown substantial improvements in their physicochemical, mechanical, electrical and biological properties, achieving excellent response. for stem cell adhesion and differentiation.

In 2022, the Andaltec technology center (Spain) reported the development of a material from polymers derived from graphene by 3D printing with great potential for the regeneration of muscle tissue. They demonstrated that in the presence of graphene derivatives, cells contract and expand without an external stimulus, therefore, it has great potential for use in regenerative medicine.

On the other hand, the Division of Postgraduate Studies and Research (DEPeI) on Odontology, UNAM and the National School of Higher Studies (ENES) León Unit, Mx., through a study published in J Oral Res 2021 supports the possibilities of graphene oxide (GO) in the design of biomaterials for dental use. The results of the research carried out with Graphenemex® GO samples, concluded that this nanomaterial in combination with polymethylmethacrylate (PMMA), in addition to improving its physical-mechanical properties, also demonstrated good compatibility and an interesting stimulation of cell proliferation when being evaluated on cultures with gingival-fibroblasts, dental-pulp-cells and human osteoblasts.

In 2020, researchers from the University of Malaga (Spain) published another study that identified GO as the ideal material for regenerative medicine. The study carried out on an animal model, showed high biocompatibility of different types of graphene oxide with dopaminergic cells, favoring their maturation and protecting them from the toxic conditions of Parkinson’s disease. These results postulate GO as an adequate scaffold to test new drugs or develop constructs for cell replacement therapy of Parkinson’s disease.

Despite the large amount of research on the interactions of graphene materials with biological media, there is still a long way to go to have these biomaterials available and in clinical operation. Energeia- Graphenemex, the pioneering Mexican company in Latin America in the research and development of applications with graphene materials, in collaboration with other companies and research centers, seeks to contribute with science to understand these interactions in a security framework, to lay solid foundations on the use of graphene nanotechnology in the biomedical sector for the benefit of society.

Drafting: EF/DHS

References

  1. Graphene and its derivatives: understanding the main chemical and medicinal chemistry roles for biomedical applications. J Nanostructure Chem, 2022, 12:693
  2. Biological and physico-mechanical properties of poly (methyl methacrylate) enriched with graphene oxide as a potential biomaterial. J Oral Res 2021; 10(2):1
  3. Graphene-Based Antimicrobial Biomedical Surfaces. ChemPhysChem 2021, 22, 250
  4. Functionalized Graphene Nanoparticles Induce Human Mesenchymal Stem Cells to Express Distinct Extracellular Matrix Proteins Mediating Osteogenesis. Int J Nanomed 2020:15 2501
  5. Graphene Oxide and Reduced Derivatives, as Powder or Film Scaffolds, Differentially Promote Dopaminergic Neuron Differentiation and Survival. Front. Neurosci., 21 December 2020. Sec. Neuropharmacology Volume 14
  6. International Journal of Nanomedicine 2019:14 5753
  7. Biocompatibility Considerations in the Design of Graphene Biomedical Materials. Adv. Mat. Interfaces 2019, 6, 1900229
  8. Graphene based scaffolds on bone tissue engineering. Bioengineered, 2018, 9:1, 38
  9. When stem cells meet graphene: Opportunities and challenges in regenerative medicine. Biomaterials, 2018, 155, 236
  10. Graphene-based materials for tissue engineering. Adv. Drug Deliv. Rev. 2016,105, 255

Chapter 92 e: Tissue Engineering, Anthony Atala. 2023 McGraw Hill.