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Rheumatoid arthritis (RA) is a chronic disease that causes destruction of bone and articular cartilage. It is a condition that results in an important target on the field for the development of biomaterials aiming to improve the health of patients with RA. In a research from the “Asociación Mexicana de Familiares y Pacientes con Artritis Reumatoide” (AMEPAR) (2017), it was found that Mexico has a prevalence of 1.6%, which ranks this country within the range of countries with a high percentage of rheumatoid arthritis.
As stated by a research from Pan et al. (2020), currently, there are treatments against RA, such as drug therapy, however it could induce adverse effects, including infection, interstitial lung disease, and impaired metabolism. Another alternative is surgery, which requires a major surgery and unavailability to be used repeatedly. Nowadays, researchers are looking for a method with a good healing effect that prevents the complications of the disease, so finding a treatment with small or none adverse reactions is a problem to be solved.
In this article, the use of a specific hydrogel combined with other compounds as a treatment for RA is reviewed. Specifically, it focuses on the use of a combined black phosphorus nanosheets (BPNs) with a platelet-rich plasma (PRP)-chitosan thermoresponsive hydrogel (Pan et al., 2020).
Among the biomaterials used in the treatment of RA, BPNs with PRP-chitosan are preferred over others for a set of reasons. Each component serves a purpose that does not interfere, or is interfered, by other materials, which means they can work synergically in a specific location. Each of the properties of the components are briefly reviewed on the following sections.
Black Phosphorus Nanosheets (BPNs)
In accordance with Yang (2019), this material can exert heat energy on its surrounding, this function makes it a good candidate to destroy diseased areas. BPNs have the capability to generate reactive oxygen species that help eliminate hyperplastic synovial tissue, which is an overgrown tissue product of cell proliferation. BPNs possess a series of properties that, when set in the synovial tissue, allows them to prevent cell proliferation, friction between bones, and the stiffening of the joints, the most common problems associated with RA.
Platelet-Rich Plasma (PRP)
Platelets are a type of blood cells whose function is to group in areas where the skin has been damaged and form clots to stop bleeding. In accordance with Everts et al. (2020), PRP is a helpful component as it supports the three phases of wound healing and repair cascade (inflammation, proliferation, remodeling).
PRP is a sample of the plasma from a patient that has a high concentration of platelets (Figure 1). This is injected back into the affected area to accelerate the healing process. The huge advantage that comes with this component is that, since the plasma used is from the same patient, there is no risk of an immunological response or rejecting behavior from the body, hence the reliability on this treatment.
Figure 1. Components of the Platelet-Rich Plasma. Everts et al., (2020)
Chitosan
It is a biodegradable polymer that occurs naturally from chitin, which is the main component of the exoskeleton in crustaceans. Chitosan is the main component of the hydrogel studied, furthermore, it has a wide array of functions: one of them is the protection of the cartilage in the zone where is injected, it can also be used as a transport for anti-inflammatory drugs which is a major advantage when it comes to treating RA. As specified by Keong and Sukari (2009), chitosan has a high biodegradability, biocompatibility, and non-toxic properties.
Chitosan thermosensitive hydrogel can be effectively used for drug delivery and sustained release due to its biodegradability, good biocompatibility, and temperature sensitivity of hydrogel formation at body temperature. Additionally, cells can adhere to grow in thermosensitive hydrogel. When chitosan is polymerized, it acquires chemical properties superior to unmodified chitosan. All the previous biomaterials can be combined with the BPNs to create a plethora of advantages that make this combination a promising tool for novel applications in RA treatment (Figure 2) (Pan et al., 2020).
Figure 2. Schematic illustration of the PRP-Chitosan thermoresponsive hydrogel combined with black phosphorus nanosheets as injectable biomaterial (Pan et al., 2020)
The components studied in this review are already regulated and have been tested to evaluate the history and evolution of tissue response once the biomaterial is applied. Among the regulations that cover the usage of the components involved in the hydrogel, the following are relevant to prove safety in the use of medical area.
- ISO 10993-6:2016 specifies test methods for the assessment of the local effects after implantation of biomaterials intended for use in medical devices.
- ISO/TS 80004-13:2017, this documentation was prepared by Technical Committee ISO/TC 229, Nanotechnologies, and IEC/TC 113, Nanotechnology for electrotechnical products and systems.
Furthermore, a research from Fang et al (2014), stated that chitosan has been determined “Generally Recognized as Safe” (GRAS) by the FDA, ensuring it doesn’t have any repercussions over the life of an individual.
Conclusions
The characteristics of the compound obtained after combining all the biomaterials gives them unique chemical properties that make them suitable in the treatment of RA. The combination of BPN/PRP/Chitosan thermoresponsive hydrogel still needs to be studied to prevent any damage in the process or any unwanted secondary side effect. Although this research is in a somewhat early stage, its results are quite promising, and could be a great candidate for a non-invasive solution for patients suffering from rheumatoid arthritis in the future, improving the possibility diseased people have to regain their quality of life and independence.
References
Asociación Mexicana de Familiares y Pacientes con Artritis Reumatoide A.C. (AMEPAR). (2017). CIFRAS EN MÉXICO. AMEPAR. https://amepar.org.mx/cifras-en-mexico/
Everts, P., Onishi, K., Jayaram, P., Fábio, J., & Mautner, K. (2020, 21 octubre). Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020. MDPI. https://www.mdpi.com/1422-0067/21/20/7794/htm
Fang, L., Wolmarans, B., Kang, M., Jeong, K. C., & Wright, A. C. (2014). Application of Chitosan Microparticles for Reduction of Vibrio Species in Seawater and Live Oysters (Crassostrea virginica). Applied and Environmental Microbiology, 81(2), 640–647. https://doi.org/10.1128/aem.02856-14
Gallardo-Villagrán, M., Yannick, D., Liagre, B., & Therrien, B. (2019, 7 julio). Photosensitizers Used in the Photodynamic Therapy of Rheumatoid Arthritis. MDPI. https://www.mdpi.com/1422-0067/20/13/3339
ISO – International Organization for Standardization. (2016). ISO 10993-6:2016. Retrieved April 27, 2021, from ISO website: https://www.iso.org/standard/61089.html
Keong, L., & Sukari, A. (2009, 18 marzo). In Vitro Models in Biocompatibility Assessment for Biomedical-Grade Chitosan Derivatives in Wound Management. MDPI. https://www.mdpi.com/1422-0067/10/3/1300/htm
Pan, W., Dai, C., Li, Y., Yin, Y., Gong, L., Machuki, J. O., Gao, F. (2020). PRP-chitosan thermoresponsive hydrogel combined with black phosphorus nanosheets as injectable biomaterial for biotherapy and phototherapy treatment of rheumatoid arthritis. Biomaterials, 239, 119851. https://doi.org/10.1016/j.biomaterials.2020.119851
Yang, X. (2019, March 27). Functional black phosphorus nanosheets for mitochondria-targeting photothermal/photodynamic synergistic cancer therapy. Chemical Science (RSC Publishing). https://pubs.rsc.org/en/content/articlelanding/2019/sc/c8sc04844d#!divAbstract
(2021). Retrieved April 28, 2021, from Iso.org website: https://www.iso.org/obp/ui/#iso:std:iso:ts:80004:-13:ed-1:v1:en
About the authors
Dielci Karina Martínez Gutiérrez
6th semester student in the Biomedical Engineering degree, member of the SOMIB-UDLAP Student Chapter
Alejandro David León Medrano
6th semester student in the Biomedical Engineering degree, member of the SOMIB-UDLAP Student Chapter
Last modified: 11 mayo, 2021