Thanoon, W., Majid, O., Marie, A. (2025). Local Effect of Insulin on Healing of Extraction Socket (Experimental Study). , 25(1), 16-38. doi: 10.33899/rdenj.2023.139627.1204
Waqass S Thanoon; Omer Waleed Majid; Ali Khalil Marie. "Local Effect of Insulin on Healing of Extraction Socket (Experimental Study)". , 25, 1, 2025, 16-38. doi: 10.33899/rdenj.2023.139627.1204
Thanoon, W., Majid, O., Marie, A. (2025). 'Local Effect of Insulin on Healing of Extraction Socket (Experimental Study)', , 25(1), pp. 16-38. doi: 10.33899/rdenj.2023.139627.1204
Thanoon, W., Majid, O., Marie, A. Local Effect of Insulin on Healing of Extraction Socket (Experimental Study). , 2025; 25(1): 16-38. doi: 10.33899/rdenj.2023.139627.1204

Local Effect of Insulin on Healing of Extraction Socket (Experimental Study)

Al-Rafidain Dental Journal
Article 2, Volume 25, Issue 1, March 2025, Pages 16-38    PDF (1.06 M)
Document Type: Research Paper
DOI: 10.33899/rdenj.2023.139627.1204
Authors
Waqass S Thanoon* 1; Omer Waleed Majid1; Ali Khalil Marie2
1Department of Oral and Maxillofacial Surgery, College of Dentistry, University of Mosul/ Iraq.
2Department of Prosthodontics, College of Dentistry, University of Mosul/ Iraq, School of Dentistry, University of Leeds, United Kingdom.
Abstract
Aims: The present study aims to investigate the effect of insulin on the healing of rabbits' dental sockets. Evaluating oral mucosa healing and bone regeneration of the healing process during three intervals 3-, 10- and 30-days post-extraction. Materials and Methods: Twelve male albino rabbits were used in this study, randomly subdivided into three sub-groups (N=4) for the histological and immunohistochemistry evaluation at 3, 10, and 30 days post-extraction and compared to the controls. The rabbits were euthanized at the corresponding time interval, each rabbit represented a control and treated sample. Bilateral maxillary first premolar extraction (treated side and control side) was performed, followed by treatment injection into the socket. A gel foam cylindrical insert of (3*5 mm) dimensions was placed in both sockets. For the treated groups; a standardized dose 10 IU in 0.1 ml from a solution of 100 IU/ml concentration of Insulin; for each corresponding group was injected into the gel foam whilst in the socket of the treated side, while for the control side (was kept plain without injection). A secondary post-extraction standardized dose was split equally and injected buccally and palataly around the gingival margins of the studied socket on the 2nd, 4th, and 6th-day post extraction only for the treated side. For each study interval, rabbits in each group were euthanized. Specimens from the oral mucosa and maxillary alveolar bone from the extraction sockets with sufficient margins were immediately harvested and arranged for laboratory examination. Assessment of inflammatory response, granulation tissue formation, re-epithelialization, bone healing, and the expression of CD34 and Ki67 was performed. Non-parametric statistical analysis was performed, and significance was recorded at p≤0.05. Results: Histological evaluation results revealed a significantly reduced inflammation response, reduced granulation tissue formation, higher and quicker re- epithelialization and enhanced bone formation for treated group when compared to the control at certain time intervals within the total period of the study. The Immunohistochemistry results revealed a significantly increased expression of CD34 and Ki67 markers in the treated group as compared to the control groups at certain study intervals. Conclusions: Within the limits of the present study, local application of Insulin demonstrated a positive effect on the healing process of oral mucosa as well as bone regeneration of the dental socket. The local injection of Insulin would be a suitable candidate to be used in the enhancement of post-extraction healing.
Keywords
Insulin,,; ,،,؛healing,,; ,،,؛tooth socket
Supplementary Files
References
  1. Abd Elrahman, S.M., Younes, S.A. and Kawana, K.Y. Effect of Nigella Sativa on Socket Healing in Rabbits. Alexandria Dental Journal, 2019; 44, 60-64.
  2. Hassan, M.A. and AL-Ghaban NM. Histological Evaluation of the Effect of Local Application of Grape Seed Oil on Healing Process of Extracted Tooth Socket in Rabbits. Diyala Journal of Medicine, 2019; 17, 2.
  3. Liu, X., Zhang, X., Tian, X., Chen, J. and He, Y. Effect of Osteogenic Inducer Sustained Release System on Bone Remodeling after Tooth Extraction. Acts Universitatis Medicinalis Anhui,2021; 56 (5): 823-827.
  4. Macedo A.S., Mendes, F., Filipe, P., Reis, S. and Fonte, P. Nanocarrier-Mediated Topical Insulin Delivery for Wound Healing. Materials,2021;14, 4257.
  5. Yang, S., Li, Y., Liu, C., Wu, Y., Wan, Z. and Shen, D. Pathogenesis and Treatment of Wound Healing in Patients with Diabetes after Tooth Extraction. Front. Endocrinol.,2022; 13 (94953), 5.
  6. Kaur, P. and Choudhury, D. Insulin Promotes Wound Healing by Inactivating Nfkβ P50/P65 and Activating Protein and Lipid Biosynthesis and Alternating Pro/Anti-Inflammatory Cytokines Dynamics. BioMol Concepts,2019; 10: 11-24.
  7. Wang, J. and Xu, J. Effects of Topical Insulin on Wound Healing: A Review of Animal and Human Evidences. Diabetes Metab Syndr Obes,2020; 13: 719-727.
  8. David, R. and Rajkumar, N.A. Comparative Study to Assess the Effectiveness of Topical Insulin Dressing Vs Normal Saline Dressing on Wound Healing of Diabetic Foot Ulcer. Int. J. Res Pharm. Sci, 2020; 11, 134-138.
  9. AbdelKader, DH, Osman MA, Elgizawy SA, Faheem AM, and McCarron PA. The role of insulin in wound healing process: Mechanism of action and pharmaceutical applications. J. Anal. Pharm. Res. 2018; 2: 1–6.
  10. Azevedo, F., Pessoa, A., Moreira, G., Dos, S., M, Liberti, E, Araujo, E, Carvalho, C, Saad, M, Lima and M, H. Effect of Topical Insulin on Second-Degree Burns in Diabetic Rats. Biol. Res Nurs,2016; 18 (2), 181-192.
  11. De Waard, E., Driessen, J., and De Jong, J. The Association between Insulin Use and Volumetric Bone Mineral Density, Bone Micro-Architecture and Bone Strength of the Distal Radius in Patients with Type 2 Diabetes - the Maastricht Study. Bone, 2017; 101, 156-161.
  12. Nyman, J.S., Kalaitzoglou, E., Clay Bunn, R., Uppuganti, S., Thrailkill, K.M. and Fowlkes, J.L. Preserving and Restoring Bone with Continuous Insulin Infusion Therapy in a Mouse Model of Type 1 Diabetes. Bone Rep,2017; 7: 1-8.
  13. Mahmoud, H.M., Sheriff, H., Ismael, A., and Zaki, A. Effect of Topical Insulin Administration on Bone Defect Healing in Diabetic Rats. Braz Dent SciApr/Jun,2020; 23, 2.
  14. Mapara, M., Thomas, B.S. and Bhat, K. Rabbit as an Animal Model for Experimental Research. Dent Res J, 2012, 9(1): 111-118.
  15. Pandian, S. Ketamine-Xylazine anaesthesia in rabbits. Indian Vet. J.2005; 82(4): 388–389.
  16. Callis, G. and Sterchi, D. Decalcification of Bone: Literature Review and Practical Study of Various Decalcifying Agents. Methods, and Their Effects on Bone Histology. Journal of Histotechnology, 1998; 21 (1), 49-58.
  17. Yousif, M.Q., Qasem, S.a.M.Q. and Qasem, S.A. Tissue Processing and Staining for Histological Analyses, Academic Press Elsevier Inc. San Diego United States.2016.
  18. Pity, I.S. and Jalal, J.A. (2013). Expression of Ki-67 and P53 in Oral Squamous Epithelial Abnormalities. Medical Journal of Babylon, 10 (1), 85-99.
  19. Mohammed Immediate  augmentation  of  extraction socket using bone substitute prepared from Iraqi gypsum rock (an experimental study) on  dogs.  PhD  thesis.  Collage  of  dentistry,  university  of  Mosul. Mosul, Iraq. 2014.
  20. Lucaciu, O., Gheban, D., Soriţau, O., Băciuţ, M., Câmpian, R.S. and Băciuţ, G. Comparative Assessment of Bone Regeneration by Histometry and a Histological Scoring System. The Romanian Journal of Laboratory Medicine,2015; 23 (1): 31-45.
  21. Gupta, A. and Kumar, P. Assessment of the Histological State of the Healing Wound. Plast Aesthet Res, 2015 (2), 239-242.
  22. Sinha,   K.,  and  Gallagher,  L.A. Effects  of  steel  scalpel ultrasonic scalpel, CO2 laser, and monopolar and bipolar electrosurgery on wound healing in guinea pig oral mucosa. Laryngoscope. 2003; 113(2): 228-236.
  23. Alemi, H., Asghari, A., Abedi, G., Akbarzadeh, A. and Mortazavi, P. Effect of a Nanocomposite Containing Ostrich Eggshell on Calvarium Healing in the Rabbit: A Pathologic Study. J Hellenic Vet Med Soc, 2019; 70 (4):1757-1770.
  24. Pity, S.,  and  Ibrahim,  S.N.  Cellular  Proliferation  in  Oral Mucosal  Atypia. I J  of  Sci  &  Eng Res. (2013). 4(2): 1–4.
  25. Alsaegh, M.A., Altaie, A.M. and Zhu, S. p63 expression  And Its Relation to Epithelial Cells Proliferation in Dentigerous Cyst Odontogenic Keratocyst, and Ameloblastoma. Pathol Oncol Res, 2020; 26 (2): 1175-1182.
  26. Kitson, S., Sivalingam, V.N., and Bolton, J. Ki-67 in Endometrial Cancer: Scoring Optimization and Prognostic Relevance for Window Studies. Official journal of the United States and Canadian academy of pathology, 2017; 30: 459-468.
  27. Fedchenko, N. and Reifenrath, J. Different Approaches for Interpretation and Reporting of Immunohistochemistry Analysis Results in the Bone Tissue -- a Review. Diagnostic Pathology, 2014; 9 (221), 1-12.
  28.  Quitério, M., Simões, S., Ascenso, A., Carvalheiro, M., Leandro, A.P., Correia, I., Viana, A.S., Faísca, P., Ascensão, L., and Molpeceres, J. Development of a Topical Insulin Polymeric Nanoformulation for Skin Burn Regeneration: An Experimental Approach. Int. J. Mol. Sci, 2021; 22, 4087.
  29. Hrynyk, M. and Neufeld, R.J. Insulin and Wound Healing. Burns, 2014; 40 (8), 1433-1446.
  30. Pastar, I., Stojadinovic, O., Yin, N.C., Ramirez, H., Nusbaum, A.G., Sawaya, A., Patel, S.B., Khalid, L., Isseroff, R.R. and Tomic-Canic, M. Epithelialization in Wound Healing: A Comprehensive Review. Adv Wound Care, 2014; 3 (7): 445-464.
  31. Mirhoseini, M., Kianezhad, M.A., Rezaeipour, B., Ghasemi, M., Gatabi, Z.R., Nia, H.S. and Amiri, F.T. The Synergistic Effect of Topical Insulin and Clindamycin on Acute Dermal Wound Healing in Rat Model: A Histological Study. Journal of Histotechnology. 2021.
  32. Martinez-Jimenez, M.A., Valadez-Castillo, F.J., and Aguilar-Garcia, J. Effects of Local Use of Insulin on Wound Healing in Non-Diabetic Patients. Plastic Surg, 2018; 26 (2): 75-79.
  33. Ehterami, A., Salehi, M., and Farzamfar, S. In Vitro and in Vivo Study of Pcl/Coll Wound Dressing Loaded with Insulin-Chitosan Nanoparticles on Cutaneous Wound Healing in Rats ' Model. Int J Biol Macromol,2018; 117: 601-609.
  34.  Besson, J., Hernandes, L., Campos, J.M., Morikawa, K.A., Bersaniamado, C.A. and Matioli, G. Insulin Complexed with Cyclodextrins Stimulates Epithelialization and Neovascularization of Skin Wound Healing in Rats. Injury, 2017;48 (11): 2417-2425.
  35.  Abianeh, S.H., Bajestani, S.M., Rahmati, J., Shahrbaf, M.A. and Shirzad, N. The Effect of Local Insulin Injection on the Healing Process of Split Thickness Skin Graft Donor Site: A Randomized, Double-Blind, Placebo Control Clinical Trial. European Journal of Plastic Surgery, 2020; 3-3.
  36.  Cirmanova, V., Zofkova, I., Kasalicky, P., Lanska, V., Bayer, M., Starka, L. and Kanceva, R. Hormonal and Bone Parameters in Pubertal Girls. Physiol. Res, 2017; 66 (Suppl. 3), S419-S424.
  37. Shah,V.N.,Carpenter R.D., Ferguson V.L., and Schwartz, A.V. Bone Health in Type 1 Diabetes. Curr. Opin. Endocrinol. Diabetes Obes, 2018; 25: 231-236.
  38. Cao, W., Li, J., Yang, K. and Cao, D. (2021). An Overview of Autophagy: Mechanism, Regulation and Research Progress. Bull. Cancer, 108, 304-322.
  39. Mu, W., Liang, G., Feng, Y., Jiang, Y. and Qu, F. The Potential Therapeutic Role of Metformin in Diabetic and Non-Diabetic Bone Impairment. Pharmaceuticals, 2022; 15, 1274.
  40. Thomas, N., Chittoria, R.K., Gupta, S., Reddy, C.L., Mohan, P.B. and Shijina, K. Role of Topical Insulin in Venous Ulcer Management. Arch Med Case Rep,2020; 2 (1), 20-22.
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