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Teixeira-Santos, R.; Belo, S.; Vieira, R.; Mergulhão, F.J.M.; Gomes, L.C. Graphene-Based Composites for Biomedical Applications. Encyclopedia. Available online: (accessed on 23 June 2024).
Teixeira-Santos R, Belo S, Vieira R, Mergulhão FJM, Gomes LC. Graphene-Based Composites for Biomedical Applications. Encyclopedia. Available at: Accessed June 23, 2024.
Teixeira-Santos, Rita, Samuel Belo, Rita Vieira, Filipe J. M. Mergulhão, Luciana C. Gomes. "Graphene-Based Composites for Biomedical Applications" Encyclopedia, (accessed June 23, 2024).
Teixeira-Santos, R., Belo, S., Vieira, R., Mergulhão, F.J.M., & Gomes, L.C. (2023, December 19). Graphene-Based Composites for Biomedical Applications. In Encyclopedia.
Teixeira-Santos, Rita, et al. "Graphene-Based Composites for Biomedical Applications." Encyclopedia. Web. 19 December, 2023.
Graphene-Based Composites for Biomedical Applications

The application of graphene-based materials in medicine has led to significant technological breakthroughs. The remarkable properties of these carbon materials and their potential for functionalization with various molecules and compounds make them highly attractive for numerous medical applications. To enhance their functionality and applicability, extensive research has been conducted on surface modification of graphene (GN) and its derivatives, including modifications with antimicrobials, metals, polymers, and natural compounds. 

graphene-based materials surface modification antimicrobial activity biocompatibility biomedical applications

1. Introduction

In recent years, graphene materials have attracted significant interest due to their remarkable properties and various applications. Graphene (GN) is a two-dimensional carbon allotrope composed of a single layer of carbon atoms arranged in a hexagonal lattice [1]. This structure, which has a high surface area and large aspect ratio, confers high electronic and thermal conductivities to GN, as well as superior mechanical strength [2][3][4]. In addition, GN exhibits a high ability to interact with other molecules through various processes, including physical and chemical interactions [5].
Graphene derivatives can be generated by introducing oxygen-containing functional groups to the GN structure or reducing its oxide form, obtaining graphene oxide (GO) or reduced graphene oxide (rGO) [6], respectively. Additionally, GN monolayers can be modified with metals, antimicrobial drugs, polymers, and natural compounds [7][8][9][10]. While these derivatives preserve their original properties, they also offer enhanced advantages, such as improving the GN dispersion factor in solvents or polymeric matrices and reducing GN toxicity [11][12][13]. As a result, GN has been applied in numerous industries, including construction [14], energy [15], food [16], environmental [17], and biomedical [18].
Within the medical field, there have been notable technological advances in the application of GN and its derivatives in drug/gene delivery, biosensing, bioimaging [19], wound healing [20], and tissue engineering [18]. Furthermore, due to the antimicrobial activity and biocompatibility of GN-based materials, they are deemed suitable for manufacturing implantable medical devices such as cardiovascular stents, orthopaedic scaffolds, and urinary implants [21][22].

2. Graphene Modified with Antimicrobials

One desirable feature of graphene is its capacity to bind to a variety of molecules, including antimicrobial agents, peptides, and biocides. This capability not only broadens the range of potential applications of GN materials but also has the potential to enhance their antimicrobial activity and biocompatibility [23]. Table 1 summarizes recent studies that assessed the biocompatibility and antimicrobial performance of GN materials modified with antimicrobial compounds, including antibiotics [24], antimicrobial peptides [8][25][26], and disinfectants [27].
Table 1. Studies focusing on the biocompatibility and antimicrobial activity of graphene modified with antimicrobials.
Graphene Material Biomedical Application Biocompatibility Microorganism Main Conclusions Ref.
Doxycycline (Dox)-graphene oxide (GO) immobilized on titanium (TiO2) Medical devices Dox-GO/TiO2 did not affect the viability of human fibroblasts (over 80% cell viability). Escherichia coli
Staphylococcus aureus
Dox-GO/TiO2 reduced the viability of adhered bacteria by over 90%, whereas the GO/TiO2 surface inactivated adhered bacteria by 40%. [24]
Antimicrobial peptide (CATH-2)–reduced graphene oxide (rGO) Medical devices Functionalized rGO induced low cytotoxicity towards erythrocytes in comparison to rGO alone. E. coli Peptide-functionalized rGO exhibited higher antimicrobial activity compared to rGO (13.3- and 21.8-mm inhibition halo). [25]
Antimicrobial peptide (ponericin G1)/growth factor (bFGF)/poly(lactide-co-glycolide (PLGA)-GO composite Wound healing Produced composite increased cell proliferation compared to PLGA (p < 0.05). E. coli
S. aureus
Ponericin G1/PLGA-GO reduced bacteria growth compared to PLGA or PLGA-GO composite (p < 0.05). [8]
Antimicrobial peptide (OH30)/polyethylene glycol (PEG)-GO Wound healing OH30/PEG-GO had high cell viability (over 80%) and low toxicity. S. aureus In vitro data demonstrated that OH30 released by the synthesized composite inhibited S. aureus growth by up to 95% after 3 h. In vivo data indicated that, on day 7, the number of S. aureus in wounds containing the composite was 6 times less than OH30 or PEG-GO (p < 0.05). [26] *
N-halamine-GO fibrous membrane NS NP E. coli Synthesized composite exhibited high biocidal activity against E. coli (>90%). [27]
NP, Not Performed; NS, Not Specified; *, in vivo study.

3. Graphene Modified with Metals

Various metals and metal oxides have been utilized to modify the surface of GN and its derivatives in order to enhance their antimicrobial activity. Metals are known for their strong antimicrobial properties against a wide range of pathogens [28][29][30]. However, their biocompatibility can vary depending on factors such as the type of metal chosen and the method of conjugation.
Table 2 presents studies that have evaluated the antimicrobial activity and biocompatibility of GN materials modified with metals or metal oxides. Several authors have focused on surface-modifying GO [31][32] or rGO [33][34] with silver nanoparticles (AgNPs). The resulting composites exhibited higher inactivation rates against both Gram-positive and Gram-negative bacteria, with the exception of the composite synthesized and tested by Wierzbicki et al. [31] against Salmonella enteritidis (approximately 50% reduction. The modification of GN-based materials with AgNPs results in a synergistic effect, as they inactivate bacteria by interacting with proteins and enzymatic thiol groups [33]. Furthermore, composites containing AgNPs appear safe for medical use.
Table 2. Studies addressing the biocompatibility and antimicrobial activity of graphene modified with metals.
Graphene Material Biomedical Application Biocompatibility Microorganism Main Conclusions Ref.
Silver nanoparticles (AgNPs)-reduced graphene oxide (rGO) Medical textiles NP Escherichia coli AgNPs-rGO composites exhibited enhanced activity against E. coli (100% inactivation) compared to rGO (82.5% inactivation). [33]
AgNPs-graphene oxide (GO) NE The viability of human cells was not changed when incubated on nanoplatforms coated with AgNPs-GO. Salmonella enteritidis AgNPs-GO nanoplatform significantly inhibited S. enteritidis growth (over 50% cell inactivation). [31]
AgNPs-rGO immobilized into polyurethane/cellulose acetate matrix Wound healing In vivo data demonstrated that AgNPs-rGO-based film significantly promoted the wound healing process. Pseudomonas aeruginosa
Staphylococcus aureus
The produced film exhibited an inactivation rate of 100% for Gram-negative bacteria and 95% against Gram-positive bacteria. [34] *
AgNPs-GO deposited on nickel-titanium alloy Medical devices NP Streptococcus mutans AgNPs-GO reduced the number of S. mutans viable cells by up to 5 Log. [32]
Gold (Au)-decorated amine-functionalized graphene oxide (NH2-GO) Implant devices Au-NH2-GO did not affect the viability of human cells (approximately 100% viability). Bacillus subtilis
E. coli
P. aeruginosa
S. aureus
The synthesized material exhibited a higher (5-fold more) antibacterial activity against Gram-positive and Gram-negative bacteria than bare Au or NH2-GO material. [35]
Copper oxide (CuO)-GO nanohybrids into bacterial cellulose (BC) matrix NS CuO-GO/BC film exhibited excellent biocompatibility towards fibroblast cells (>100%). B. subtilis
E. coli
P. aeruginosa
S. aureus
After 3 h, CuO-GO/BC films completely inactivated Gram-positive bacteria while only reducing the viability of Gram-negative bacteria by 20%. [28]
CuO-rGO NS NP P. aeruginosa CuO-rGO composites led to complete bacterial inactivation (7 Log reduction). [29]
Copper nanoparticles (CuNPs)-graphene (GN) supported on silicon (Si) wafers NS CuNPs-GN/Si showed slight toxicity for human cells (15% reduction in cell viability). E. coli
S. aureus
In the presence of CuNPs-GN/Si films, S. aureus growth was completely inhibited, and E. coli viability was reduced by 87%. [30]
Palladium (Pd)/polypyrrole (PPy)-rGO composite Tissue engineering Pd/PPy-rGO (<100 µg/mL) did not substantially affect osteoblast viability (>80%). B. subtilis
E. coli
Klebsiella pneumoniae
P. aeruginosa
Pd/PPy-rGO nanocomposite significantly inhibited the biofilm formation of B. subtilis (72%), E. coli (90%), K. pneumoniae (89%), and P. aeruginosa (83%). [36]
Cerium oxide (CeO2)-GO Wound healing NP E. coli
P. aeruginosa
S. aureus
Salmonella typhi
CeO2-GO nanocomposite inhibited E. coli, P. aeruginosa, S. aureus, and S. typhi biofilms by 38, 40, 31, and 35%, respectively. [37]
NP, Not Performed; NS, Not Specified; *, in vivo study.

4. Graphene Modified with Polymers

Graphene surface modification with polymers is an interesting approach that can offer several advantages, including enhanced GN dispersion and improved mechanical properties and biocompatibility [38][39]. In addition, the association with polymers can potentially increase the antimicrobial activity of GN-based materials, as the polymers serve as a matrix that helps GN dispersion [40], thus promoting contact with microorganisms. Furthermore, some polymers have inherent antimicrobial properties because they contain cationic groups that can facilitate interactions with bacteria [41][42].
Table 3 summarizes studies addressing the biocompatibility and antimicrobial activity of GN materials modified with natural and non-natural polymers. Both pristine GN and GO have been modified with various polymers for potential medical applications (e.g., tissue engineering, wound dressing, or implantable medical devices).
Table 3. Studies reporting the biocompatibility and antimicrobial activity of graphene modified with polymers.
Graphene Material Biomedical Application Biocompatibility Microorganism Main Conclusions Ref.
Non-natural polymers          
Polyoxyalkyleneamine (POAA)-graphene oxide (GO) Surface coatings NP Bacillus subtilis
Escherichia coli
After 3 h, bacteria exposed to POAA-GO decreased their viability to at least 75%. [43]
Poly(ε-caprolactone) (PCL)-GO Tissue engineering Human fibroblasts kept their culturability and proliferation for up to 14 days. E. coli
Staphylococcus epidermidis
PCL-GO composites inactivated S. epidermidis and E. coli adhered cells by 80% after 24 h. [44]
PCL-graphene (GN) Nasal implants NP E. coli
Staphylococcus aureus
The efficacy of PCL-GN against S. aureus was about 90%. In contrast, this composite did not exhibit activity against E. coli. [41]
Epoxy-rich-GO (er-GO) Wound dressing Human cells exposed to er-GO exhibited viability ratios greater than 100%. E. coli
S. aureus
er-GO composite decreased in vitro E. coli and S. aureus viability by up to 57 and 97%, respectively. In vivo data indicated that E. coli and S. aureus viability was reduced by 47 and 68%, respectively, in presence of er-GO. [45] *
Poly(Lactic-co-Glycolic Acid) (PLGA)-graphene nanoplatelets (GNP) NE NP E. coli At 15 MHz, PLGA-GNP composites reduced E. coli viability by 33%, while at lower frequencies (10 and 5 MHz), these films decreased bacteria viability by up to 60%. [9]
Polydimethylsiloxane (PDMS)-GNP Implantable medical devices NP Pseudomonas aeruginosa
S. aureus
The PDMS-GNP reduced the number of total (57%), viable (69%), culturable (55%), and VBNC cells (85%) of S. aureus biofilms. A decrease of 25% in total cells and about 52% in viable, culturable, and VBNC cells was observed for P. aeruginosa biofilms. [46]
Natural polymers          
Chitosan (CS)-graphene oxide (GO) Surface coatings NP B. subtilis
E. coli
After 3 h, bacteria exposed to CS-GO composite decreased their viability to less than 10%. [43]
CS/poly(vinyl alcohol) (PVA)-GO nanocomposites Tissue engineering After 30 days of film implantation, the absence of injuries in the intervened areas with normal healing was observed. Bacillus cereus
S. aureus
E. coli
Salmonella spp.
Biocomposites containing 0.75 and 1 wt.% GO completely inhibited pathogen growth. [47] *
CS/PVA-GO Wound healing CS/PVA-GO hydrogels showed nontoxicity towards pre-osteoblast cells (>70% cell viability). E. coli
S. aureus
Hydrogels exhibited high antimicrobial activity against E. coli and S. aureus (up to 35 and 32 mm inhibition halo, respectively). [10]
CS/polyethylene glycol (PEG)-decorated GO biocomposite Wound healing Cell survival on CS/PEG-GO was 95.4%. E. coli
S. aureus
CS, 1 wt% CS/GO and 1 wt% CS/PEG-GO were able to inactivate S. aureus by 80, 85, and 100% and E. coli by 65, 85, and 95%, respectively. [48]
Carboxymethyl Chitosan (CC)-GO-based Sponge Wound healing CC/L-cysteine-GO sponge showed a high cell viability rate, as demonstrated by Live/Dead staining. E. coli
S. aureus
In vivo data indicated that the CC/L-cysteine-GO sponge had a faster wound-healing rate than CC/GO. In vitro tests revealed that the addition of L-cysteine-GO and GO to CC increased sponges’ antimicrobial activity. [49] *
Folic acid (FA)/silk fibroin (SF)-GO Wound healing
Tissue engineering
The viability of fibroblast cells exposed to FA/SF-GO for 24 h was 97%. P. aeruginosa After 24 h, FA/SF-GO film reduced biofilm formation by 80% compared to control (polystyrene). [50]
NP, Not Performed; NS, Not Specified; VBNC, viable but non-culturable; *, in vivo study.

5. Graphene Modified with Natural Compounds

Owing to their biodegradability, renewability, and biocompatibility, there has been growing interest in composites that incorporate natural compounds. In recent years, several natural compounds, including vivianite [51], usnic acid (UA) [52], quercetin [53], and juglone [53], have been studied in conjugation with GN composites. Table 4 presents the biocompatibility and antimicrobial activity of these modified GN materials against several Gram-positive and Gram-negative bacterial species.
Table 4. Studies demonstrating the biocompatibility and antimicrobial activity of graphene modified with natural compounds.
Graphene Material Biomedical Application Biocompatibility Microorganism Main Conclusions Ref.
Hydroxyapatite/Vivianite-GO NS Cell viability of osteoblasts in the presence of this composite was 98%. E. coli
S. aureus
Composite exhibited activity against E. coli and S. aureus after 24 h (14.5 and 13.4 mm inhibition halo, respectively). [51]
Usnic acid (UA)-GN Medical devices NP S. aureus
Staphylococcus epidermidis
After 24 h, UA-GN inhibited S. aureus and S. epidermidis biofilms by 3 Log at 25, 50, 100, and 200 µg/mL AU/GO compared to GN films and glass, except for S. aureus growing on 25 µg/mL AU-GN. After 96 h, staphylococcal biofilms were reduced by 5 Log compared to the control (glass). [52]
Quercetin-GO Drug delivery systems GO-based materials showed a biocompatible behavior at lower concentrations (>70% cell viability). E. coli
S. aureus
Quercetin/GO composites reduced S. aureus culturability by 1 Log and E. coli culturability by 5 Log. [53]
Juglone-GO Drug delivery systems Materials showed a biocompatible behavior at lower concentrations (>70% cell viability). E. coli
S. aureus
Juglone/GO composites reduced S. aureus culturability by 3 Log and E. coli culturability by 5 Log. [53]
NP, Not Performed; NS, Not Specified.

6. Conclusions

Biocompatible and antibacterial nanomaterials are in high demand for a variety of medical applications. The surface modification of GN and its derivatives (e.g., graphene oxide or reduced graphene oxide) with antimicrobials (e.g., antimicrobial peptides or biocides), metals or metal oxides, polymers, and natural compounds has enhanced the functionality and applicability of these materials, resulting in improved antimicrobial performance and increased biocompatibility towards human tissues.
The combination of graphene materials with agents that possess intrinsic antimicrobial properties, such as antimicrobial peptides, metals (silver or copper), or chitosan, enhances the effectiveness of GN materials in inactivating bacteria, especially Gram-positive bacteria, because of their less complex membrane structure. Conversely, although promising for a wide range of applications, the use of non-natural polymers for GN surface modification results in composites with lower antimicrobial activity than those obtained through the modifications mentioned above. However, GN–polymer composites exhibit superior biocompatibility compared to antimicrobial or metal-based GN composites. In the latter case, adverse effects on human cells are highly dependent on the type of metal used and the methodology employed for their production.


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