Author(s):
Nenny Prasetyaningrum, Rini D. Ridwan, Tania Saskianti, Dini Rachmawati, Regina P. Virgirinia
Email(s):
rini-d-r@fkg.unair.ac.id
DOI:
10.52711/0974-360X.2024.00820 
Address:
Nenny Prasetyaningrum1,2, Rini D. Ridwan3*, Tania Saskianti4, Dini Rachmawati1,5, Regina P. Virgirinia2
1Doctoral Program, Faculty of Dental Medicine, Universitas Airlangga, Surabaya 60132, East Java, Indonesia.
2Departement of Oral Biology, Faculty of Dental Medicine, Universitas Brawijaya, Malang 65145, East Java, Indonesia.
3Departement of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya 60132, East Java, Indonesia.
4Departement of Pediatric, Faculty of Dental Medicine, Universitas Airlangga, Surabaya 60132, East Java, Indonesia.
5Departement of Pediatric, Faculty of Dental Medecine, Universitas Brawijaya, Malang 65145, East Java, Indonesia.
*Corresponding Author
Published In:
Volume - 17,
Issue - 11,
Year - 2024
ABSTRACT:
Periodontitis causes irreversible alveolar bone resorption. Therefore, bone regeneration therapy is needed. Cell-free based regenerative therapy using secretome stem cells from exfoliated human deciduous teeth (SHED) containing growth factors, including TGF-ß, FGF-2, and VEGF, can potentially increase the bone regeneration processes through angiogenesis and osteogenesis. Hydrogels made from chitosan (CS)/Beta-glycerophosphate (ß-GP)/Hydroxyapatite (HA) can function as adhesives and control the release of bioactive contained in the secretome. This study aims to predict the role of the release of the secretome in the bone regeneration process through the binding interaction and release rate of TGF-ß, FGF-2, and VEGF proteins with the compounds that make up CS/ß-GP/ HA hydrogel through molecular docking. Three-dimensional (3D) structures for compounds and proteins obtained from the PubChem database. Docking analysis was carried out using Pyrx v.0.8 software. The molecular docking methods are used to identify bond positions and bond energies between proteins and chemical compounds. The results of molecular docking predictions for the interaction of TGF-ß, FGF-2, and VEGF binding to the CS/ß-GP/HA hydrogel constituent compounds indicated that interaction could block binding with their receptors. The most ligand interactions are found in TGF-ß with CS/BGP/HA on five amino acids, namely Trp32, His34, Try91, Arg25, and His40. FGF-2 and VEGF are each bound to one amino acid, namely Asn102 with CS and Glu64 with HA. From the results of the binding affinity analysis, it is known that TGF-ß has the strongest total binding affinity, namely -17.0 kcal/mol, followed by VEGF and FGF-2, which have total binding affinities of -15.3 kcal/mol and -13.7 kcal. It concluded that the controlled release of the SHED secretome from the CS/ß-GP/HA hydrogel base begins with the release of FGF-2 and VEGF for angiogenesis, followed by the release of TGF-ß for osteogenesis that has the potential to increase the bone regeneration in periodontitis.
Cite this article:
Nenny Prasetyaningrum, Rini D. Ridwan, Tania Saskianti, Dini Rachmawati, Regina P. Virgirinia. Prediction of Secretome Release from Hydrogels Based on Molecular Interactions and Binding Affinity to Promoting Bone Regeneration in Periodontitis. Research Journal of Pharmacy and Technology. 2024; 17(11):5368-4. doi: 10.52711/0974-360X.2024.00820
Cite(Electronic):
Nenny Prasetyaningrum, Rini D. Ridwan, Tania Saskianti, Dini Rachmawati, Regina P. Virgirinia. Prediction of Secretome Release from Hydrogels Based on Molecular Interactions and Binding Affinity to Promoting Bone Regeneration in Periodontitis. Research Journal of Pharmacy and Technology. 2024; 17(11):5368-4. doi: 10.52711/0974-360X.2024.00820 Available on: https://rjptonline.org/AbstractView.aspx?PID=2024-17-11-28
REFERENCES:
1. Hajishengallis G. Immunomicrobial Pathogenesis of Periodontitis: Keystones, Pathobionts, and Host Response. Trends Immunol. 2014; 35(1): 3-11. doi:10.1016/j.it.2013.09.001
2. Jia L, Han N, Du J, Guo L, Luo Z, Liu Y. Pathogenesis of Important Virulence Factors of Porphyromonas Gingivalis Via Toll-Like Receptors. Front Cell Infect Microbiol. 2019; 9(JUL): 1-14. doi:10.3389/fcimb.2019.00262
3. Nazir M, Al-Ansari A, Al-Khalifa K, Alhareky M, Gaffar B, Almas K. Global Prevalence of Periodontal Disease and Lack of Its Surveillance. Sci World J. 2020; 2020. doi:10.1155/2020/2146160
4. Saputra G, Nugraha AP, Budhy TI, et al. Nanohydroxyapatite-Chitosan Hydrogel Scaffold with Platelet Rich Fibrin and Buccal Fat Pad derived Stem Cell for Aggressive Periodontitis Treatment: A Narrative Review. Res J Pharm Technol. 2022; 15(12): 5903-5908. doi:10.52711/0974-360X.2022.00995
5. Hienz SA, Paliwal S, Ivanovski S. Mechanisms of Bone Resorption in Periodontitis. J Immunol Res. 2015; 2015. doi:10.1155/2015/615486
6. Galli M, Yao Y, Giannobile W V., Wang HL. Current and Future Trends in Periodontal Tissue Engineering and Bone Regeneration. Plast Aesthetic Res. 2021; 2021. doi:10.20517/2347-9264.2020.176
7. Bhatt P, Bhargava A, Kamath V, Khurana C, Mukherjee P, Chhabra M. Active Leptospermum Honey as a Local Drug Delivery Agent in patients with Chronic Periodontitis: A Clinico-Biochemical Study. Res J Pharm Technol. 2022; 15(12): 5449-5454. doi:10.52711/0974-360X.2022.00918
8. Tang G, Tan Z, Zeng W, et al. Recent Advances of Chitosan-Based Injectable Hydrogels for Bone and Dental Tissue Regeneration. Front Bioeng Biotechnol. 2020; 8(September): 1-15. doi:10.3389/fbioe.2020.587658
9. Battafarano G, Rossi M, De Martino V, et al. Strategies for Bone Regeneration: From Graft to Tissue Engineering. Int J Mol Sci. 2021; 22(3): 1-22. doi:10.3390/ijms22031128
10. Brennan M, Layrolle P, Mooney DJ. Biomaterials Functionalized with MSC Secreted Extracellular Vesicles and Soluble Factors for Tissue Regeneration. Adv Funct Mater. 2020; 30(37). doi:10.1002/adfm.201909125
11. Samal HB, Niranjan Patra C, Boyeena L, Das IJ. Novel periodontal pocket drug delivery systems for the treatment of periodontitis. Indian Drugs. 2021; 58(3): 7-21. doi:10.53879/id.58.03.11958
12. Usui M, Onizuka S, Sato T, Kokabu S, Ariyoshi W, Nakashima K. Mechanism of Alveolar Bone Destruction in Periodontitis — Periodontal Bacteria and Inflammation. Jpn Dent Sci Rev. 2021; 57: 201-208. doi:10.1016/j.jdsr.2021.09.005
13. Tong S, Xu DP, Liu ZM, Du Y, Wang XK. Synthesis of and In Vitro And In Vivo Evaluation Of A Novel TGF-1-SF-CS Three-Dimensional Scaffold For Bone Tissue Engineering. Int J Mol Med. 2016; 38(2): 367-380. doi:10.3892/ijmm.2016.2651
14. Gugliandolo A, Fonticoli L, Trubiani O, et al. Oral bone tissue regeneration: Mesenchymal stem cells, secretome, and biomaterials. Int J Mol Sci. 2021; 22(10). doi:10.3390/ijms22105236
15. Chapple ILC, Linero I. Regenerative Medicine: A New Paradigm in Bone Regeneration. Adv Tech Bone Regen. 2016; (September). doi:10.5772/62523
16. Vizoso FJ, Eiro N, Cid S, Schneider J, Perez-Fernandez R. Mesenchymal stem cell secretome: Toward cell-free therapeutic strategies in regenerative medicine. Int J Mol Sci. 2017; 18(9). doi:10.3390/ijms18091852
17. Ramadhani NF, Nugraha AP, Ihsan IS, et al. Gingival medicinal signaling cells conditioned medium effect on the osteoclast and osteoblast number in lipopolysaccharide-induced calvaria bone resorption in wistar rats’ (Rattus novergicus). Res J Pharm Technol. 2021; 14(10): 5232-5237. doi:10.52711/0974-360X.2021.00911
18. Pranskunas M, Šimoliūnas E, Alksne M, et al. Assessment of the bone healing process mediated by periosteum-derived mesenchymal stem cells’ secretome and a xenogenic bioceramic—An in vivo study in the rabbit critical size calvarial defect model. Materials (Basel). 2021; 14(13). doi:10.3390/ma14133512
19. Bhandi S, Alkahtani A, Mashyakhy M, et al. Effect of Ascorbic Acid on Differentiation , Secretome and Stemness of Stem Cells from Human Exfoliated Deciduous Tooth ( SHEDs ). J Pers Med. 2021; 11: 589.
20. Konala VBR, Bhonde R, Pal R. Secretome studies of mesenchymal stromal cells (MSCs) isolated from three tissue sources reveal subtle differences in potency. Vitr Cell Dev Biol - Anim. 2020; 56(9): 689-700. doi:10.1007/s11626-020-00501-1
21. Hiraki T, Kunimatsu R, Nakajima K, et al. Stem cell-derived conditioned media from human exfoliated deciduous teeth promote bone regeneration. Oral Dis. 2020; 26(2): 381-390. doi:10.1111/odi.13244
22. Sudarmono, Sunardhi Widyaputra, Suhardjo Sitam, Inne Suherna, Arni D. Fitri A. MSC with hBMMSC as a Reference A Literature Review of Potential Bone Regeneration. Res J Pharm Technol. Published online 2021. doi:10.52711/0974-360X.2022.00995
23. Keerthic Aswin S, Jothishwar S, Visvavela Chellaih Nayagam P, Priya G. Scaffolds for biomolecule delivery and controlled release–A review. Res J Pharm Technol. 2018; 11(10): 4719-4730. doi:10.5958/0974-360X.2018.00861.2
24. Zheng W, Bai Z, Huang S, Jiang K, Liu L, Wang X. The Effect of Angiogenesis-Based Scaffold of MesoporousBioactive Glass Nanofiber on Osteogenesis. Int J Mol Sci. 2022; 23(20). doi:10.3390/ijms232012670
25. Sawant S V., Sankpal S V., Jadhav KR, Kadam VJ. Hydrogel as drug delivery system. Res J Pharm Technol. 2012; 5(5): 561-569.
26. De Witte TM, Fratila-Apachitei LE, Zadpoor AA, Peppas NA. Bone tissue engineering via growth factor delivery: From scaffolds to complex matrices. Regen Biomater. 2018; 5(4): 197-211. doi:10.1093/rb/rby013
27. Gharat JS, Dalvi Y V. Compressive Review on Hydrogel. Asian J Pharm Technol. 2018; 8(3): 172. doi:10.5958/2231-5713.2018.00028.4
28. Gobinath T, Kaviya K, Ravichandran S. Chitosan/ Ulva lactuca polysaccharide hydrogel containing copper (ii) beneficial for biofilm-associated wound infection: Formulation characterizations and In vitro study . Res J Pharm Technol. 2020; 13(9): 4224. doi:10.5958/0974-360x.2020.00746.5
29. Dang Q, Liu K, Zhang Z, et al. Fabrication and evaluation of thermosensitive chitosan/collagen/α, β-glycerophosphate hydrogels for tissue regeneration. Carbohydr Polym. 2017; 167: 145-157. doi:10.1016/J.CARBPOL.2017.03.053
30. Marabathuni VJ, Dinesh P, Ravikumar R, et al. Chitosan Based Sustained Release Mucoadhesive Buccal Patches Containing Amlodipine Besylate (AMB). Asian J Res Pharm Sci. 2017; 7(2): 97. doi:10.5958/2231-5659.2017.00015.7
31. Xu X, Gu Z, Chen X, et al. An injectable and thermosensitive hydrogel: Promoting periodontal regeneration by controlled-release of aspirin and erythropoietin. Acta Biomater. 2019; 86: 235-246. doi:10.1016/j.actbio.2019.01.001
32. Wang Y, Cao X, Ma M, Lu W, Zhang B, Guo Y. A GelMA-PEGDA-nHA composite hydrogel for bone tissue engineering. Materials (Basel). 2020; 13(17). doi:10.3390/MA13173735
33. Rabab Kamel, Nahla A. El-Wakil NAE. Injectable hydrogel scaffolds composed of Nanocellulose derived from sugarcane bagasse and combined with calcium for Bone regeneration. Research Journal of Pharmacy and Technology. doi:https://doi.org/10.52711/0974-360X.2023.00569
34. Jain PK, Gilhotra R, Kori ML. Drug Release and Mucoadhesive behavior of Hydrogel in Chemo-Radiotherapy induced Oral Mucositis. Res J Pharm Technol. 2019; 12(6): 2838. doi:10.5958/0974-360x.2019.00478.5
35. Rambhia KJ, Ma PX. Controlled Drug Release for Tissue Engineering. J Control Release. 2015; 219: 119-128. doi:10.1016/j.jconrel.2015.08.049.Controlled
36. Vishwajit S. Patil PAP. Molecular Docking A useful approach of Drug Discovery on the Basis of their Structure. Asian J Pharm Res. 2023; 19(3): 191-195.
37. Earle Radha Rani, M. Ramadevi ALU. An Overview on Hydrophilic three-Dimensional Networks Hydrogels. Asian J Pharm Res. 2021; 11(1): 23-28.
38. Hermanto FE, Warsito W, Rifa’i M, Widodo N. On the Hypolipidemic Activity of Elicited Soybeans: Evidences Based on Computational Analysis. Indones J Chem. 2022; 22(6): 1626. doi:10.22146/ijc.75777
39. Dallakyan S, Olson A. Small-Molecule Library Screening by Docking with PyRx. Methods Mol Biol. 2015; 1263: 243–250. doi:10.1007/978-1-4939-2269-7
40. Pawar RP, Rohane SH. Role of Autodock vina in PyRx Molecular Docking. Asian J Res Chem. 2021; 14(2): 132-134.
41. Radaev S, Zou Z, Huang T, Lafer EM, Hinck AP, Sun PD. Ternary complex of transforming growth factor-β1 reveals isoform-specific ligand recognition and receptor recruitment in the superfamily. J Biol Chem. 2010; 285(19): 14806-14814. doi:10.1074/jbc.M109.079921
42. Plotnikov AN, Hubbard SR, Schlessinger J, Mohammadi M. Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity. Cell. 2000; 101(4): 413-424. doi:10.1016/S0092-8674(00)80851-X
43. Peach CJ, Mignone VW, Arruda MA, et al. Molecular pharmacology of VEGF-A isoforms: Binding and signalling at VEGFR2. Int J Mol Sci. 2018; 19(4). doi:10.3390/ijms19041264
44. Trott O, Olson AJ. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2009; 31(2): NA-NA. doi:10.1002/jcc.21334
45. H. Saeed H, Al-Saffar MT, S. Mahmood A. Effects of Rosuvastain on Bone Healing. Res J Pharm Technol. Published online 2023: 2705-2708. doi:10.52711/0974-360x.2023.00444
46. Misra PS, Ravichandiran V, Vijey Aanandhi M. Design, synthesis and in silico molecular docking study of n-carbamoyl-6-oxo-1-phenyl-1, 6-dihydropyridine-3-carboxamide derivatives as fibroblast growth factor 1 inhibitor. Res J Pharm Technol. 2017; 10(8): 2527-2534. doi:10.5958/0974-360X.2017.00447.4
47. Musfiroh I, Azura AR, Rahayu D. Prediction of Asiatic Acid Derivatives Affinity Against SARS-CoV-2 Main Protease Using Molecular Docking. Pharm Sci Res. 2020; 7(4): 57-64. doi:10.7454/psr.v7i4.1086
48. Arifka M, Wilar G, Elamin KM, Wathoni N. Polymeric Hydrogels as Mesenchymal Stem Cell Secretome Delivery System in Biomedical Applications. Polymers (Basel). 2022; 14(6): 1-19. doi:10.3390/polym14061218