Effect of Cinnamaldehyde, an Anti-Inflammatory Agent, on the Surface Characteristics of a Plaster of Paris – CaCO3 Hydrogel for Bone Substitution in Biomedicine
Corresponding email: ikadewiana@ugm.ac.id
Published at : 27 Nov 2020
Volume : IJtech
Vol 11, No 5 (2020)
DOI : https://doi.org/10.14716/ijtech.v11i5.4313
Dewi, A.H., Yulianto, D.K., Ana, I.D., Rochmadi, Siswomihardjo, W., 2020. Effect of Cinnamaldehyde, an Anti-Inflammatory Agent, on the Surface Characteristics of a Plaster of Paris – CaCO3 Hydrogel for Bone Substitution in Biomedicine . International Journal of Technology. Volume 11(5), pp. 963-973
| Anne Handrini Dewi | Department of Dental Biomedical Sciences, Faculty of Dentistry, Universitas Gadjah Mada |
| Dedy Kusuma Yulianto | Department of Dental Biomedical Sciences, Faculty of Dentistry, Universitas Gadjah Mada |
| Ika Dewi Ana | Department of Dental Biomedical Sciences, Faculty of Dentistry, Universitas Gadjah Mada |
| Rochmadi Rochmadi | Department of Chemical Engineering, Faculty of Engineering, Universitas Gadjah Mada |
| Widowati Siswomihardjo | Department of Dental Biomaterials, Faculty of Dentistry, Universitas Gadjah Mada |
Combining an anti-inflammatory agent derived from a plant essential oil, such as cinnamaldehyde, with bioabsorbable and osteoconductive material as a bone substitute is a challenge in biomedical technology. In this study, cinnamaldehyde, a good anti-inflammatory agent with an aromatic ?, ?-unsaturated aldehyde derived from cinnamon, was loaded in composites of plaster of Paris (POP) and calcium carbonate (CaCO3) hydrogel as a bone substitute. However, during blood–biomaterial interactions, which start after surgical implantation, blood protein adsorption to the biomaterial surface occurs prior to interaction with host cells. Therefore, before a device is ready for implantation, the influence of cinnamaldehyde on the property of the composite, especially its surface characteristics, needs to be examined. The aim of this research was to investigate the effect of cinnamaldehyde on the surface topography, contact angle, and surface roughness of a POP–CaCO3 hydrogel scaffold. The results indicate that cinnamaldehyde increased the contact angle and surface roughness of the POP hydrogel, which seemed to be homogenous on all surfaces.
Bone substitute; CaCO3 hydrogel; Cinnamaldehyde; POP; Surface characteristics
A variety of
ceramics have been used to treat bone defects (Anzelme, 2000; Ooms
et al., 2002; Orsini et al., 2004; Chao et al., 2005). One of them,
calcium sulfate (CS) or plaster of Paris (POP), known to be a resorbable
material, has shown the ability to enhance bone regeneration (Cirotteau, 2001). However, a disadvantage of
using CS is related to its fast resorption rate during the osteogenesis
process, making it unable to provide a long-term three-dimensional framework (Fenaroli, 2016; Dewi et al., 2013; Dewi et al., 2015).
To solve this problem, in previous studies, biocompatible and osteoconductive
hydrogel calcium carbonate (CaCO3) has been incorporated into CS
formulations (Gomes et al., 2011; Dewi et al.,
2015).
From a biomedical
perspective, the implantation of medical devices often leads to a foreign body
reaction related to the accumulation and activation
of inflammatory cells in
In view of the phenomenon, it would be advantageous if cinnamaldehyde (CA),
previously described as an essential oil and known to be an anti-inflammatory
agent (Jamali
et al., 2002; Kim et al.,
2010, Jakethia et al., 2010), could be
incorporated into an implant device. Interesting
results have been found when CA was loaded in a PLGA hydrogel (Gomes et al., 2011) and a CaCO3
hydrogel (Dewi et al., 2013). It was found
that the incorporation of CA is beneficial as an anti-microbial and
anti-inflammatory agent (Dewi et al., 2015; Dewi et
al., 2017). However, since CA can be both lipophilic and hydrophilic, this can
affect the mechanical and surface properties of a composite. Additionally,
surface properties, especially surface chemistry, hydrophilicity, and surface
topography, influence the interactions between cells and substrates in the
environment surrounding implanted material (Pal et
al., 2009) because in a living host, blood plasma is the first component
to contact implant material. Further rapid adsorption of plasma protein occurs
on the surface of biomaterial prior to cell attachment, spreading,
proliferation, and differentiation (Jimbo et al.,
2010).
Surface topography and hydrophilicity can influence the attachment of
cells in different ways. Hydrophilicity, a result of surface chemistry, is
correlated to the wettability of an implant surface (Gittens
et al., 2014). A material is categorized
as hydrophilic when the contact angle between the material and a water
droplet is <90° (Yulianto and Margareta, 2014).
Hydrophilic surfaces are important for promoting a good environment for bone
formation (Boyan
et al., 2017). Additionally, smooth surfaces allow cells to attach
and spread more than rough surfaces, and high wettability combined with a
microrough surface stimulates more anti-inflammatory cytokine release by
macrophages than a hydrophilic but smooth surface (Hotchkiss
et al., 2016).
Surface properties, especially chemistry, hydrophilicity, and
topography, are known to influence the interaction between cells and substrates
in the environment surrounding implanted materials. This study demonstrated
that CA as an anti-inflammatory agent can be successfully loaded into CaCO3
hydrogel prior to the incorporation of the hydrogel into POP to form POP–CaCO3
hydrogel composites. The results indicated that adding CA to a hydrogel system
increased the contact angle, but it was still <90o (i.e.
hydrophilic). The surface roughness of the POP–CaCO3 hydrogel was
also increased. Increased contact angle and surface roughness may influence
blood protein adsorption and cell attachment; therefore, we propose carrying
out investigations of the in vitro cytotoxicity and in vivo
animal studies in our laboratory.
This study was financed by the Faculty of Dentistry, Universitas Gadjah
Mada Grant Aid, contract number 6031/KG/PP/2014-2019 as a part of the
fulfillment of Anne Handrini Dewi’s PhD. The publication of this study is part
of the World Class University Program supported by the Indonesian Ministry of
Research and Technology/National Agency for Research and Innovation managed by
Institut Teknologi Bandung (award number 1913G/I1.B04.2/SPP/2020).
| Filename | Description |
|---|---|
| R2-MME-4313-20201024054532.png | Figure 1 in PNG |
| R2-MME-4313-20201024055022.png | Figure 2 in PNG |
| R2-MME-4313-20201024055049.png | Figure 3 in PNG |
| R2-MME-4313-20201024055142.png | Figure 4 in PNG |
| R2-MME-4313-20201024055411.png | Figure 5 in PNG |
| R2-MME-4313-20201024055646.png | Figure 6 in PNG |
| R2-MME-4313-20201024060032.png | Figure 7 in PNG |
| R2-MME-4313-20201024060412.png | Figure 8 in PNG |
| R2-MME-4313-20201024060917.pdf | Highlighted Revised Manuscript in PDF |
| R2-MME-4313-20201024061032.pdf | Cover Letter Including Responses to Reviewers in PDF |
Anzelme,
K., 2000. Osteoblast Adhesion on Biomaterials. Biomaterials, Volume 21(7), pp. 667–681
Barleany, D.R., Ananta, C.V., Maulina,
F., Rochmat, A., Erizal, H.A., 2020. Controlled Release of Metformin Hydrogen
Chloride from Stimuli-responsive Hydrogel based on
Poly-(N-Isopropylacrylamide)/Chitosan/Polyvinyl Alcohol Composite. International
Journal of Technology, Volume 11(3), pp. 511–521
Boyan,
B.D., Lotz, E.M., Schwartz, Z., 2017. Roughness and Hydrophilicity as Osteogenic
Biomimetic Surface Properties. Tissue Eng:
Part A, Volume 23(23-24), pp. 1479–1489
Chao,
L.K., Hua, K.F., Hsu, H.Y., Cheng, S.S., Liu, J.Y., Chang, S.T., 2005. Study on
the Antiinflammatory Activity of Essential Oil from Leaves of Cinnamomum
osmophleum. Journal of Agricultural and Food Chemistry, Volume 53(18), pp. 7274–7278
Cirotteau, Y., 2001. Behavior of Natural Coral
in a Human Osteoporotic Bone. Eur J
Orthop Surg Traumatol,
Volume 11, pp. 149–160
Da Silva, C.M., Da Silva, D.L., Modolo, L.V.,
Alves, R.B., De Resende, M.A., Martins, C.V.B., De Fa’tima, A., 2011. Schiff
bases: A Short Review of Their Antimicrobial Activities. J Adv Res,
Volume 2(1), pp. 1–8
Dewi,
A.H., Ana, I.D., Wolke, J.G.C., Jansen, J.A., 2013. Behavior of Plaster of
Paris-calcium Carbonate Composite as Bone Substitute. A Study in Rats. J
Biomed Mater Res A, Volume 101(8),
pp. 2143–2150
Dewi,
A.H., Ana, I.D., Wolke, J.G.C., Jansen, J.A., 2015. Behavior of POP–calcium Carbonate
Hydrogel as Bone Substitute with Controlled Release Capability: A Study in Rat.
J Biomed Mater Res A, Volume
103(10), pp. 3273–3283
Dewi,
A.H., Ana, I.D., Jansen, J.A., 2015. Calcium Carbonate Hydrogel Construct with Cinnamaldehyde
Incorporated to Control Inflammation during Surgical Procedure. J Biomed
Mater Res A, Volume 104A, pp. 768–774
Dewi,
A.H., Ana, I.D., Jansen, J.A., 2017. Preparation of a Calcium Carbonate-based Bone
Substitute with Cinnamaldehyde Crosslinking Agent with Potential Anti-inflammatory
Properties. J Biomed Mater Res A, Volume 105(4), pp. 1055–1062
Elfani, M., Putra, N.K., 2013. Biomedical Engineering
and Its Potential for Employment in Indonesia. International Journal of Technology, Volume 4(1), pp. 34–44
Fenaroli,
G., 2016. Fenaroli’s Handbook of Flavour
Ingredients. 4th Edition. Boca Raton:
CRC
Gittens,
R.A., Scheideler, L., Rupp, F., Hyzy, S.L., GeisGerstorfer, J., Schwartz, Z.,
Boyan, B.D., 2014. A Review on the Wettability of Dental Implant Surfaces II: Biological
and Clinical Aspects. Acta Biomater, Volume 10(7), pp. 2907–2918
Gomes,
C., Moreira, R.G., Perez, E.C., 2011. Poly (DL-lactide-co-glycolide) (PLGA) Nanoparticles
with Entrapped Trans-cinnamaldehyde and Eugenol for Antimicrobial Delivery Applications.
J Food Sci, Volume 76(2),
pp. 16–24
Hallab,
N.J., Bundy, K.J., O’Connor, K., Moses, R.L., Jacobs, J.J., 2001. Evaluation of
Metallic and Polymeric Biomaterial Surface Energy and Surface Roughness Characteristics
for Directed Cell Adhesion. Tissue Eng, Volume 7(1), pp. 55–71
Higueras,
L., Carballo, G.L., Gavara, R., Munoz, P.H., 2015. Reversible Covalent Immobilization
of Cinnamaldehyde on Chitosan Films via Schiff Base Formation and Their Application
in Active Food Packaging. Food Bioprocess Technol, Volume 8(3), pp. 526–538
Hotchkiss,
K.M., Reddya, G.B., Hyzya, S.L., Schwartza, Z., Boyan, B.D., Olivares, N.,
2016. Titanium Surface Characteristics, Including Topography and Wettability, Alter
Macrophage Activation. Acta Biomater, Volume 31, pp. 425–434
Jakhetia,
V., Patel, R., Khatri, P., Pahuja, N., Garg, S., Pandey, A., Sharma, S., 2010.
Cinnamon: Pharmacological Review. J Adv Sci Res, Volume 1(2), pp. 19–23
Jamali,
A., Hilpert, A., Debes, J., Afshar, P., Rahban, S., Holmes, R., 2002.
Hydroxyapatite/Calcium Carbonate (HA/CC) vs. Plaster of Paris: A
Histomorphometric and Radiographic Study in a Rabbit Tibial Defect Model. Calcif
Tissue Int, Volume 71(2),
pp. 172–178
Jimbo,
R., Ivarsson, M., Koskela, A., Sul, Y., Johansson, C.B., 2010. Protein Adsorption to Surface Chemistry
and Crystal Structure Modification of Titanium Surfaces. J Oral Maxillofac
Res, Volume 1(3), pp. e3-p.1
Kim,
B.H., Lee, Y.G., Lee, J., Lee, J.Y., Cho, J.Y., 2010. Regulatory Effect of Cinnamaldehyde
on Monocyte/Macrophage-mediated Inflammatory Responses. Mediat Inflamm, Volume
2010, pp. 1–9
Krisanti, E.A., Hijrianti, N., Mulia, K., 2019.
Preparation and Evaluation of Alginate-chitosan Matrices Loaded with Red Ginger
Oleoresin using the Ionotropic Gelation Method. International Journal of Technology, Volume 10(8),
pp. 1513–1522
Mazor,
Z., Mamidwar, S., Ricci, J.L., Tovar, N.M., 2011. Bone Repair in Periodontal
Defect using a Composit of Allograft and Calcium Sulfate (Dentogen) and a
Calcium Sulfate Barrier. J Oral Implantol, Volume 37(2), pp. 287–292
Mazzola,
L., Bemporad, E., Carassiti, F., 2012. An Easy Way to Measure Surface Free
Energy by Drop Shape Analysis. Measurement, Volume 45, pp. 317–324
Meiron,
T.S., Marmur, A., Saguy, I.S., 2004. Contact Angle Measurement on Rough Surfaces.
J Colloid Interface Sci, Volume
274, pp. 637–644
Ojagh,
S.M., Rezaei, M., Razavi, S.H., Hosseini, S.M.H., 2010. Development and Evaluation
of a Novel Biodegradable Film Made from Chitosan and Cinnamon Essential Oil
with Low Affinity Toward Water. Food Chemistry, Volume 122(1), pp. 161–166
Ooms,
E.M., Wolke, J.G.C., Waerden, J.P.C.M., Jansen, J.A., 2002. Trabecular Bone Response
to Injectable Calcium Phosphate (Ca-P) Cement. J Biomed Mater Res,
Volume 61, pp. 9–18
Orsini,
G., Ricci, J., Scarano, A., Pecora, G., Petrone, G., Lezzi, G., Piatelli, A.,
2004. Bone-defect Healing with Calcium-sulfate Particles and Cement: An Experimental
Study in Rabbit. J Biomed Mater Res B, Volume 68B, pp. 199–208
Pal,
K., Banthia, A.K., Majumdar, D.K., 2009. Polymeric Hydrogels: Characterization and
Biomedical Applications- A Mini Review. Designed Monomers and Polymers,
Volume 12(3), pp. 197–220
Park,
S., Zhao, Y., 2004. Incorporation of a High Concentration of Mineral or Vitamin
into Chitosan-based Films. J Agric Food Chem, Volume 52(7), pp.
1933–1939
Peng,
Y., Li, Y., 2014. Combined Effects of Two Kinds of Essential Oils on Physical,
Mechanical and Structural Properties of Chitosan Films. Food Hydrocolloids,
Volume 36, pp. 287–293
Peter,
M., Ganesh, N., Selvamurugan, N., Nair, S.V., Furuike, T., Tamura, H.,
Jayakumar, R., 2010. Preparation and Characterization of Chitosan-gelatin/ Nanohydroxyapatite
Composite Scaffolds for Tissue Engineering Applications. Carbohydrate
Polymers, Volume 80(3), pp. 687–694
Piao,
C., Winandy, J.E., Shupe, T.F., 2010. From Hydrophilicity to Hydrophobicity: A Critical
Review: Part I. Wettability and Surface Behavior. Wood and Fiber Science: Journal
of the Society of Wood Science and Technology, Volume 42(4), pp. 490–510
Pogorzelskia,
S.J., Berezowskib, Z., Rochowskia, P., Szurkowskia, J., 2012. A Novel Methodology
based on Contact Angle Hysteresis Approach for Surface Changes Monitoring in Model
PMMA-Corega Tabs System. Applied Surf Sci, Volume 258(8), pp. 3652–3658
Sahlan, M., Fadhan, A.M., Pratami, D.K., Wijanarko,
A., Lischer, K., Hermansyah, H., Mahira, K.F., 2019. Encapsulation of Agarwood Essential
Oil with Maltodextrin and Gum Arabic. International Journal of Technology, Volume 10(8), pp. 1541–1547
Supova,
M., 2009. Problem of Hydroxyapatite Dispersion in Polymer Matrices: A Review. J
Mater Sci. Mater Med, Volume 20, pp. 1201–1213
Shupe, F., Hse, C.Y., Choong, E.T., Groom,
L.H., 1998. Effect of Wood Grain and Veneer Side on Loblolly Pine Veneer Wettability.
Forest Prod J, Volume 48(6), pp. 95–97
Thomas,
M.V., Puleo, D.A., 2009. Calcium Sulfate: Properties and Clinical Application. J
Biomed Mater Res B, Volume
88(2), pp. 597–610
Tung,
Y.T., Chua, M., Wang, S., Chang, S., 2008. Anti-inflammation Activities of Essential
Oil and Its Constituents from Indigenous Cinnamon (Cinnamomum osmophloeum) Twigs.
Bioresource Technol, Volume
99(9), pp. 3908–3913
Wu,
Y.C., Min Lee, T., Hsun Chiu, K., Yu Shaw, S., Yu Yang, C., 2009. A Comparative
Study of the Physical and Mechanical Properties of Three Natural Corals based on
the Criteria for Bone–tissue Engineering Scaffolds. Journal of Materials
Science Materials in Medicine, Volume 20(6), pp. 1273–1280
Vogler,
E.A., 2012. Protein Adsorption in Three Dimensions. Biomaterials, Volume
33(5), pp. 1201–1237
Xu,
L., Bauer, J., Siedlecki, C.A., 2014. Protein, Platelets, and Blood Coagulation
at Biomaterial Interfaces. Colloid Surf B Biointerfaces, Volume 124, pp.
49–68
Yorur,
H., Erer, A.M., O?uz, S., 2017. Effect of Surface Roughness on Wettability of
Adhesive on Wood Substrates. In: The 3rd International Conference
on Science, Ecology and Technology, Rome, Italy, 14–16 August
Youn,
H.S., Lee, J.K., Choi, Y.J., Saitoh, S.I., Miyake, K., Hwang, D.H., Lee, J.Y.,
2008 Cinnamaldehyde Suppresses Toll-like Receptor 4 Activation Mediated through
the Inhibition of Receptor Oligomerization. Biochem Pharmacol, Volume 75(2),
pp. 494–502
Yulianto,
H.D.K., Margareta, R., 2014. Contact Angle Measurement of Dental Restorative Materials.
Jurnal Tekno Sains, Volume 3(2), pp. 112–119
Zaika,
L.L., 1988. Spices and Herbs: Their Antibacterial Activity and Its Determination.
J Food Saf, Volume
9(2), pp. 97–118
Zdolsek, J., Eaton, J.W., Tang, L., 2007. Histamine Release
and Fibrinogen Adsorption Mediate Acute Inflammatory Responses to Biomaterial
Implants in Humans. J Transl Med, Volume 5(31), pp. 1–6