Acemannan from Aloe Vera: A Promising Biological Agent for Osteoinductive Applications in Guided Bone Regeneration
Received: 2023-07-14
Revised: 2023-09-20
Accepted: 2023-09-27
Published in Issue 2025-08-19
Copyright (c) 2025 Copyright © 2024, The Author(s), under exclusive licence to Islamic Azad University

This work is licensed under a Creative Commons Attribution 4.0 International License.
How to Cite
Abstract
Aim: This systematic review investigates the osteoconductive properties of acemannan, a principal polysaccharide derived from Aloe vera, in the context of guided bone regeneration (GBR). With the growing interest in biological agents for bone healing, this study aims to elucidate the role of acemannan in enhancing bone regeneration outcomes.
Materials and methods: A comprehensive search was conducted across multiple electronic databases such as Embase, PubMed, Scopus, Web of Science, and Google Scholar for studies published between 2000 and 2023. Two independent researchers screened the literature, removing duplicates and irrelevant articles to focus on experimental studies, case reports, and clinical trials that specifically examined the effects of acemannan on bone regeneration.
Results and discussion: From an initial pool of 185 studies retrieved, 16 eligible articles were selected for review, comprising nine experimental studies, four clinical trials, and two case reports/case series. The findings indicate that A. vera and acemannan promote osteogenic differentiation, reduce inflammation, and enhance bone healing, making them promising agents for dental and orthopedic applications.
Conclusion: This review highlights the potential of acemannan and Aloe vera as effective biological agents in bone regeneration strategies. The evidence suggests that acemannan promotes osteogenic differentiation, reduces inflammation, and improves overall bone healing outcomes. Further research is warranted to explore its applications in clinical settings, particularly in enhancing GBR techniques.
Keywords
- Acemannan,
- Aloe vera,
- Bone Regeneration,
- Tissue Engineering,
- Guided Bone Regeneration
References
- Abtahi, S., Chen, X., Shahabi, S. & Nasiri, N. 2023. Resorbable membranes for guided bone regeneration: critical features, potentials, and limitations. ACS Materials Au, 3, 394-417. https://doi.org/10.1021/acsmaterialsau.3c00013
- Abu-Seida, A. M. A.-S. & Heba, S. 2023. Aloe vera in dentistry: current status and future prospects. International Arab Journal of Dentistry (IAJD), 14, 188-199. https://doi.org/10.70174/iajd.v14i2.943
- Al-Fakeh, H., Sharhan, H. M., Ziyad, T. A., Abdulghani, E. A., Al-Moraissi, E., Al-Sosowa, A. A., Liu, B. & Zhang, K. 2022. Three-dimensional radiographic assessment of bone changes around posterior dental implants at native bone site in Gansu Province, Northwest of China: A retrospective cohort study. Journal of Stomatology, Oral and Maxillofacial Surgery, 123, e186-e191. https://doi.org/10.1016/j.jormas.2022.04.005
- Amirian, J., Linh, N. T. B., Min, Y. K. & Lee, B.-T. 2015. Bone formation of a porous Gelatin-Pectin-biphasic calcium phosphate composite in presence of BMP-2 and VEGF. International journal of biological macromolecules, 76, 10-24. https://doi.org/10.1016/j.ijbiomac.2015.02.021
- Andabak-Rogulj, A., Vindiš, E., Aleksijević, L. H., Škrinjar, I., Juras, D. V., Aščić, A. & Brzak, B. L. 2023. Different treatment modalities of oral lichen planus—a narrative review. Dentistry journal, 11, 26. https://doi.org/10.3390/dj11010026
- Bai, Y., Niu, Y., Qin, S. & Ma, G. 2023. A new biomaterial derived from Aloe vera—Acemannan from basic studies to clinical application. Pharmaceutics, 15, 1913. https://doi.org/10.3390/pharmaceutics15071913
- Baldwin, P., Li, D. J., Auston, D. A., Mir, H. S., Yoon, R. S. & Koval, K. J. 2019. Autograft, allograft, and bone graft substitutes: clinical evidence and indications for use in the setting of orthopaedic trauma surgery. Journal of orthopaedic trauma, 33, 203-213. http://doi.org/10.1097/BOT.0000000000001420
- Banerjee, D. & Bose, S. 2019. Effects of aloe vera gel extract in doped hydroxyapatite-coated titanium implants on in vivo and in vitro biological properties. ACS Applied Bio Materials, 2, 3194-3202. https://pubs.acs.org/doi/abs/10.1021/acsabm.9b00077
- Boonyagul, S., Banlunara, W., Sangvanich, P. & Thunyakitpisal, P. 2014. Effect of acemannan, an extracted polysaccharide from Aloe vera, on BMSCs proliferation, differentiation, extracellular matrix synthesis, mineralization, and bone formation in a tooth extraction model. Odontology, 102, 310-317. https://doi.org/10.1007/s10266-012-0101-2
- Bucchi, C., Del Fabbro, M., Arias, A., Fuentes, R., Mendes, J. M., Ordonneau, M., Orti, V. & Manzanares-Céspedes, M.-C. 2019. Multicenter study of patients’ preferences and concerns regarding the origin of bone grafts utilized in dentistry. Patient preference and adherence, 179-185. https://doi.org/10.2147/PPA.S186846
- Chan, B. & Leong, K. 2008. Scaffolding in tissue engineering: general approaches and tissue-specific considerations. European spine journal, 17, 467-479. https://doi.org/10.1007/s00586-008-0745-3
- Chansamart, R., Sangvanich, P. & Thunyakitpisal, P. 2023. Clinical and radiographic evaluation of combined acemannan and periodontal surgery induced-periodontal regeneration: 5-year follow-up case report. The Open Dentistry Journal, 17. https://doi.org/10.2174/18742106-v17-e230124-2022-75
- Chantarawaratit, P., Sangvanich, P., Banlunara, W., Soontornvipart, K. & Thunyakitpisal, P. 2014. Acemannan sponges stimulate alveolar bone, cementum and periodontal ligament regeneration in a canine class II furcation defect model. Journal of periodontal research, 49, 164-178. https://doi.org/10.1111/jre.12090
- Chow, J. T.-N., Williamson, D. A., Yates, K. M. & Goux, W. J. 2005. Chemical characterization of the immunomodulating polysaccharide of Aloe vera L. Carbohydrate research, 340, 1131-1142. https://doi.org/10.1016/j.carres.2005.02.016
- Dalai, R. P., Riyaz, S. M. A., Awinashe, M., Almutairy, M., Sidhu, R., Amlutairi, F. J. & Ramaiah, V. V. 2023. Assessment of Aloe Vera and Tulsi’s Effectiveness in Treating Oral Submucous Fibrosis. Journal of Pharmacy and Bioallied Sciences, 15, S1136-S1138. http://doi.org/10.4103/jpbs.jpbs_190_23
- Darzi, S., Paul, K., Leitan, S., Werkmeister, J. A. & Mukherjee, S. 2021. Immunobiology and application of aloe vera-based scaffolds in tissue engineering. International journal of molecular sciences, 22, 1708. https://doi.org/10.3390/ijms22041708
- Deesricharoenkiat, N., Jansisyanont, P., Chuenchompoonut, V., Mattheos, N. & Thunyakitpisal, P. 2022. The effect of acemannan in implant placement with simultaneous guided bone regeneration in the aesthetic zone: a randomized controlled trial. International Journal of Oral and Maxillofacial Surgery, 51, 535-544. https://doi.org/10.1016/j.ijom.2021.07.017
- Egierska, D., Perszke, M., Mazur, M. & Duś-Ilnicka, I. 2023. Platelet-rich plasma and platelet-rich fibrin in oral surgery: A narrative review. Dental and Medical Problems, 60, 177-186. https://doi.org/10.17219/dmp/147298
- Ferraz, M. 2023garcia. Bone grafts in dental medicine: an overview of autografts, allografts and synthetic materials. Materials (Basel). 2023; 16: 4117. https://doi.org/10.3390/ma16114117
- García-García, A., Pigeot, S. & Martin, I. 2023. Engineering of immunoinstructive extracellular matrices for enhanced osteoinductivity. Bioactive Materials, 24, 174-184. https://doi.org/10.1016/j.bioactmat.2022.12.017
- García-Gareta, E., Coathup, M. J. & Blunn, G. W. 2015. Osteoinduction of bone grafting materials for bone repair and regeneration. Bone, 81, 112-121. https://doi.org/10.1016/j.bone.2015.07.007
- Ghoname, N., Yagi, A., Gonna, S., Kabbash, A. & Deraz, E. M. 2017. Acemannan and formocresol pulpotomies in primary teeth: a comparative histopathological study. Journal of Gastroenterology and Hepatology Research, 6, 2386-2391. https://doi.org/10.17554/j.issn.2224-3992.2017.06.711
- Godoy, D. J. D., Chokboribal, J., Pauwels, R., Banlunara, W., Sangvanich, P., Jaroenporn, S. & Thunyakitpisal, P. 2018. Acemannan increased bone surface, bone volume, and bone density in a calvarial defect model in skeletally-mature rats. Journal of Dental Sciences, 13, 334-341. https://doi.org/10.1016/j.jds.2018.06.004
- Hamman, J. H. 2008. Composition and applications of Aloe vera leaf gel. Molecules, 13, 1599-1616. https://doi.org/10.3390/molecules13081599
- Jamnezhad, S., Asefnejad, A., Motififard, M., Yazdekhasti, H., Kolooshani, A., Saber-Samandari, S. & Khandan, A. 2020. Development and investigation of novel alginate-hyaluronic acid bone fillers using freeze drying technique for orthopedic field. Nanomedicine Research Journal, 5, 306-315. https://doi.org/10.22034/nmrj.2020.04.001
- Jansisyanont, P., Tiyapongprapan, S., Chuenchompoonut, V., Sangvanich, P. & Thunyakitpisal, P. 2016. The effect of acemannan sponges in post-extraction socket healing: A randomized trial. Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, 28, 105-110. https://doi.org/10.1016/j.ajoms.2015.07.006
- Jittapiromsak, N., Sahawat, D., Banlunara, W., Sangvanich, P. & Thunyakitpisal, P. 2010. Acemannan, an extracted product from Aloe vera, stimulates dental pulp cell proliferation, differentiation, mineralization, and dentin formation. Tissue Engineering Part A, 16, 1997-2006. https://doi.org/10.1089/ten.tea.2009.0593
- Kaparakou, E. H., Kanakis, C. D., Gerogianni, M., Maniati, M., Vekrellis, K., Skotti, E. & Tarantilis, P. A. 2021. Quantitative determination of aloin, antioxidant activity, and toxicity of Aloe vera leaf gel products from Greece. Journal of the Science of Food and Agriculture, 101, 414-423. https://doi.org/10.1002/jsfa.10650
- Kargarpour, Z., Nasirzade, J., Panahipour, L., Mitulović, G., Miron, R. J. & Gruber, R. 2021. Platelet-rich fibrin increases BMP2 expression in oral fibroblasts via activation of TGF-β signaling. International Journal of Molecular Sciences, 22, 7935. https://doi.org/10.3390/ijms22157935
- Khorasani, H. R., Sanchouli, M., Mehrani, J. & Sabour, D. 2021. Potential of Bone‐Marrow‐Derived Mesenchymal Stem Cells for Maxillofacial and Periodontal Regeneration: A Narrative Review. International Journal of Dentistry, 2021, 4759492. https://doi.org/10.1155/2021/4759492
- Kim, K., Su, Y., Kucine, A. J., Cheng, K. & Zhu, D. 2023. Guided bone regeneration using barrier membrane in dental applications. ACS Biomaterials Science & Engineering, 9, 5457-5478. https://doi.org/10.1021/acsbiomaterials.3c00690
- Kim, Y.-K. & Ku, J.-K. 2020. Guided bone regeneration. Journal of the Korean Association of Oral and Maxillofacial Surgeons, 46, 361-366. https://doi.org/10.5125/jkaoms.2020.46.5.361
- Liang, H., Mirinejad, M. S., Asefnejad, A., Baharifar, H., Li, X., Saber-Samandari, S., Toghraie, D. & Khandan, A. 2022. Fabrication of tragacanthin gum-carboxymethyl chitosan bio-nanocomposite wound dressing with silver-titanium nanoparticles using freeze-drying method. Materials Chemistry and Physics, 279, 125770. https://doi.org/10.1016/j.matchemphys.2022.125770
- Mijiritsky, E., Assaf, H. D., Kolerman, R., Mangani, L., Ivanova, V. & Zlatev, S. 2022. Autologous Platelet Concentrates (APCs) for hard tissue regeneration in oral implantology, sinus floor elevation, peri-implantitis, socket preservation, and medication-related osteonecrosis of the jaw (MRONJ): A Literature Review. Biology, 11, 1254. https://doi.org/10.3390/biology11091254
- Milinkovic, I. & Cordaro, L. 2014. Are there specific indications for the different alveolar bone augmentation procedures for implant placement? A systematic review. International journal of oral and maxillofacial surgery, 43, 606-625. https://doi.org/10.1016/j.ijom.2013.12.004
- Miron, R. J., Fujioka-Kobayashi, M., Bishara, M., Zhang, Y., Hernandez, M. & Choukroun, J. 2017. Platelet-rich fibrin and soft tissue wound healing: a systematic review. Tissue Engineering Part B: Reviews, 23, 83-99. https://doi.org/10.1089/ten.teb.2016.0233
- Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G. & Group, P. 2010. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. International journal of surgery, 8, 336-341. https://doi.org/10.1016/j.ijsu.2010.02.007
- Nasiri, P., Shafaroudi, A. M., Moosazadeh, M., Poorkazemi, D. & Sabet, J. M. 2021. The Potential of Aloe vera as an Active Ingredient in Toothpaste Formulations: A Narrative Review. Jundishapur Journal of Natural Pharmaceutical Products, 4. http://dx.doi.org/10.5812/jjnpp.117500
- Nguyen, T. M., Do, T. T. T., Tran, T. N. & Kim, J. H. 2020. Exercise and quality of life in women with menopausal symptoms: a systematic review and meta-analysis of randomized controlled trials. International journal of environmental research and public health, 17, 7049. https://doi.org/10.3390/ijerph17197049
- Niu, Y., Li, Q., Ding, Y., Dong, L. & Wang, C. 2019. Engineered delivery strategies for enhanced control of growth factor activities in wound healing. Advanced drug delivery reviews, 146, 190-208. https://doi.org/10.1016/j.addr.2018.06.002
- Poorkazemi, D., Malekzadeh Shafaroudi, A., Nasiri, P., Aarabi, M. & Mehrani Sabet, J. 2022. Evaluation of Aloe vera as a Natural Pharmaceutic in mouthwashes: a narrative review. Jundishapur J Nat Pharm Prod, 17. https://doi.org/10.5812/jjnpp-122155
- Raisi, A., Asefnejad, A., Shahali, M., Sadat Kazerouni, Z. A., Kolooshani, A., Saber-Samandari, S., Kamyab Moghadas, B. & Khandan, A. 2020. Preparation, characterization, and antibacterial studies of N, O-carboxymethyl chitosan as a wound dressing for bedsore application. Archives of Trauma Research, 9, 181-188. http://doi.org/10.4103/atr.atr_10_20
- Rao, S. S., Rekha, P., Anil, S., Lowe, B. & Venkatesan, J. 2019. Natural polysaccharides for growth factors delivery. Natural Polysaccharides in Drug Delivery and Biomedical Applications. Elsevier. https://doi.org/10.1016/B978-0-12-817055-7.00021-2
- Rasoulian, B., Almasi, A., Hoveizi, E., Bagher, Z., Hayat, P., Joghataei, M. T., Rezayat, S. M. & Tavakol, S. 2019. Strong binding active constituents of phytochemical to BMPR1A promote bone regeneration: In vitro, in silico docking, and in vivo studies. Journal of Cellular Physiology, 234, 14246-14258. https://doi.org/10.1002/jcp.28121
- Safari, B., Davaran, S. & Aghanejad, A. 2021. Osteogenic potential of the growth factors and bioactive molecules in bone regeneration. International journal of biological macromolecules, 175, 544-557. https://doi.org/10.1016/j.ijbiomac.2021.02.052
- Saito, S., Hamai, R., Shiwaku, Y., Hasegawa, T., Sakai, S., Tsuchiya, K., Sai, Y., Iwama, R., Amizuka, N. & Takahashi, T. 2021. Involvement of distant octacalcium phosphate scaffolds in enhancing early differentiation of osteocytes during bone regeneration. Acta Biomaterialia, 129, 309-322. https://doi.org/10.1016/j.actbio.2021.05.017
- Shi, Y., Wei, K., Lu, J., Wei, J., Hu, X. & Chen, T. 2020. A clinic trial evaluating the effects of aloe vera fermentation gel on recurrent aphthous stomatitis. Canadian Journal of Infectious Diseases and Medical Microbiology, 2020, 8867548. https://doi.org/10.1155/2020/8867548
- Soares, I. M. V., Fernandes, G. V. D. O., Cavalcante, L. C., Leite, Y. K. P. D. C., Bezerra, D. D. O., Carvalho, M. A. M. D. & Carvalho, C. M. R. S. 2019. The influence of Aloe vera with mesenchymal stem cells from dental pulp on bone regeneration: characterization and treatment of non-critical defects of the tibia in rats. Journal of Applied Oral Science, 27, e20180103. https://doi.org/10.1590/1678-7757-2018-0103
- Soltani, M. & Alizadeh, P. 2022. Aloe vera incorporated starch-64S bioactive glass-quail egg shell scaffold for promotion of bone regeneration. International Journal of Biological Macromolecules, 217, 203-218. https://doi.org/10.1016/j.ijbiomac.2022.07.054
- Songsiripradubboon, S., Banlunara, W., Sangvanich, P., Trairatvorakul, C. & Thunyakitpisal, P. 2016. Clinical, radiographic, and histologic analysis of the effects of acemannan used in direct pulp capping of human primary teeth: short-term outcomes. Odontology, 104, 329-337. https://doi.org/10.1007/s10266-015-0215-4
- Taalab, M. R., Rehim, S. S. A. E., Eldeeb, D. W., El-Moslemany, R. M. & Abdelrahman, H. 2023. Histologic and histomorphometric evaluation of Aloe vera adjunctive to β-tricalcium phosphate in class II furcation defects in dogs. Scientific Reports, 13, 4198. https://doi.org/10.1038/s41598-023-31282-8
- Tabatabaeian, M. & Esfahanian, V. 2023. Effect of acemannan/aloe vera on bone regeneration specially in the oral and maxillofacial region: a literature review. Journal of Research in Dental and Maxillofacial Sciences, 8, 226-235. http://dx.doi.org/10.61186/jrdms.8.3.226
- Tahmasebi, A., Moghadam, A. S., Enderami, S. E., Islami, M., Kaabi, M., Saburi, E., Farshchi, A. D., Soleimanifar, F. & Mansouri, V. 2020. Aloe vera–derived gel-blended PHBV nanofibrous scaffold for bone tissue engineering. Asaio Journal, 66, 966-973. http://doi.org/10.1097/MAT.0000000000001094
- Tao, C., Zhu, W., Iqbal, J., Xu, C. & Wang, D.-A. 2020. Stabilized albumin coatings on engineered xenografts for attenuation of acute immune and inflammatory responses. Journal of Materials Chemistry B, 8, 6080-6091. https://doi.org/10.1039/D0TB01111H
- Teymori, M., Karimi, E. & Saburi, E. 2023. Evaluation of osteoconductive effect of polycaprolactone (PCL) scaffold treated with Aloe vera on adipose-derived mesenchymal stem cells (ADSCs). American Journal of Stem Cells, 12, 83. PMID: 38021455; PMCID: PMC10658133
- Thant, A. A., Ruangpornvisuti, V., Sangvanich, P., Banlunara, W., Limcharoen, B. & Thunyakitpisal, P. 2023. Characterization of a bioscaffold containing polysaccharide acemannan and native collagen for pulp tissue regeneration. International Journal of Biological Macromolecules, 225, 286-297. https://doi.org/10.1016/j.ijbiomac.2022.11.015
- Toosi, S. & Behravan, J. 2020. Osteogenesis and bone remodeling: A focus on growth factors and bioactive peptides. Biofactors, 46, 326-340. https://doi.org/10.1002/biof.1598
- Trinh, H. A., Dam, V. V., Banlunara, W., Sangvanich, P. & Thunyakitpisal, P. 2020. Acemannan induced bone regeneration in lateral sinus augmentation based on cone beam computed tomographic and histopathological evaluation. Case Reports in Dentistry, 2020, 1675653. https://doi.org/10.1155/2020/1675653
- Turner, C. E., Williamson, D. A., Stroud, P. A. & Talley, D. J. 2004. Evaluation and comparison of commercially available Aloe vera L. products using size exclusion chromatography with refractive index and multi-angle laser light scattering detection. International Immunopharmacology, 4, 1727-1737. https://doi.org/10.1016/j.intimp.2004.07.004
- Vu, N. B., Chuenchompoonut, V., Jansisyanont, P., Sangvanich, P., Pham, T. H. & Thunyakitpisal, P. 2021. Acemannan-induced tooth socket healing: A 12-month randomized controlled trial. Journal of Dental Sciences, 16, 643-653. https://doi.org/10.1016/j.jds.2020.10.003
- Wang, R., Wang, H., Mu, J., Yuan, H., Pang, Y., Wang, Y., Du, Y. & Han, F. 2023. Molecular events in the jaw vascular unit: A traditional review of the mechanisms involved in inflammatory jaw bone diseases. Journal of Biomedical Research, 37, 313. https://doi.org/10.7555/jbr.36.20220266
- Yagi, A. 2023. Prophylaxis Role of Kampo- and Diagnosed-Drug with Butyrate Fermented in Aloe Vera Gel as an Adjuvant for Mitigating and Relieving Pain in Spinal Stenosis and Restoring of Osteoporosis. EC Clinical and Medical Case Reports, 6, 01-05.
- Zadeh Gharaboghaz, M. N., Farahpour, M. R. & Saghaie, S. 2020. Topical co-administration of Teucrium polium hydroethanolic extract and Aloe vera gel triggered wound healing by accelerating cell proliferation in diabetic mouse model. Biomedicine & Pharmacotherapy, 127, 110189. https://doi.org/10.1016/j.biopha.2020.110189