Nanomedicine Journal

Nanomedicine Journal

Hydrogels for dental pulp repair: enhancing physicochemical and regenerative potential with CaP-loaded alginate-gelatin hydrogel scaffolds: a FEM and ANN modeling

Document Type : Research Paper

Authors
Abbasali Khademi
Amirsalar Khandan
Pedram Iranmanesh
Department of Endodontics, Dental Research Center, Dental Research Institute, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran
10.22038/nmj.2025.84229.2115
Abstract
Hydrogels for dental pulp repair present a promising strategy to enhance physicochemical and regenerative potentials. This study focuses on a hydrogel matrix fabricated by combining alginate and gelatin, incorporating varying concentrations of calcium phosphate (CaP) at 0, 2, 4, and 6 wt% to evaluate their effects on the mechanical properties of hydrogels for dental pulp regeneration (DPR). Scanning electron microscopy (SEM) was employed to assess the morphological characteristics of the hydrogels. Additionally, finite element analysis (FEA) was introduced to model the conical nerve root, and an artificial neural network (ANN) model was developed to predict the relationships between composition and mechanical and biological properties. Results demonstrated that increasing CaP content enhanced tensile strength, reduced porosity, and improved pH stability, with optimal performance observed at 4 wt%. The ANN effectively explored the relationships among parameters influencing tensile strength and porosity, accurately predicting damage percentage, weight gain, and strut diameter. Linear regression analysis validated the ANN's predictions, indicating acceptable error margins relative to experimental data. Incorporation of 4 wt% CaP into the alginate-gelatin hydrogel significantly enhanced its mechanical properties, bioactivity, and stability, highlighting the potential of this novel bio-nanocomposite porous scaffold for DPR applications.
Keywords
Dental pulp regeneration
Tissue engineering
Scaffolds
Hydrogels
Calcium phosphates
3D bioprinting
  1. Eramo S, Natali A, Pinna R, Milia E. Dental pulp regeneration via cell homing. Int End J. 2018;51(4):405-419.
  2. Khademi A, Khandan A, Iranmanesh P, Heydari M. Development of a 3D Bioprinted Alginate-Gelatin Hydrogel Scaffold Loaded with Calcium Phosphates for Dental Pulp Tissue Regeneration. IJCCE. 2024.
  3. Xie Z, Shen Z, Zhan P, Yang J, Huang Q, Huang S, Chen L, Lin Z. Functional dental pulp regeneration: basic research and clinical translation. Int J Mol Sci. 2021;22(16):8991.
  4. Khandan A, Khosravi M, Roustazadeh D, Aghadavoudi F. Impact of alumina and carbon nanotubes on mechanical properties of a composite: molecular dynamic (MD) simulation. IJCCE, (Articles in Press). 2024.
  5. Itoh Y, Sasaki JI, Hashimoto M, Katata C, Hayashi M, Imazato S. Pulp regeneration by 3-dimensional dental pulp stem cell constructs. J Dent Res. 2018;97(10):1137-1143.
  6. An J, Chua CK, Mironov V. Application of machine learning in 3D bioprinting: focus on development of big data and digital twin. Int J Bioprint. 2021;7(1).
  7. Ng WL, Yeong WY, Naing MW. Polyelectrolyte gelatin-chitosan hydrogel optimized for 3D bioprinting in skin tissue engineering. Int J Bioprint. 2016;2(1):53-62.
  8. Zhang R, Xie L, Wu H, Yang T, Zhang Q, Tian Y, Liu Y, Han X, Guo W, He M, Liu S. Alginate/laponite hydrogel microspheres co-encapsulating dental pulp stem cells and VEGF for endodontic regeneration. Acta Biomater. 2020;113:305-316.
  9. Yu H, Zhang X, Song W, Pan T, Wang H, Ning T, Wei Q, Xu HH, Wu B, Ma D. Effects of 3-dimensional bioprinting alginate/gelatin hydrogel scaffold extract on proliferation and differentiation of human dental pulp stem cells. J Endod. 2019;45(6):706-715.
  10. Bhoj M, Zhang C, Green DW. A first step in de novo synthesis of a living pulp tissue replacement using dental pulp MSCs and tissue growth factors, encapsulated within a bioinspired alginate hydrogel. J Endod. 2015;41(7):1100-1107.
  11. Bendtsen ST, Quinnell SP, Wei M. Development of a novel alginate‐polyvinyl alcohol‐hydroxyapatite hydrogel for 3D bioprinting bone tissue engineered scaffolds. J Biomed Mater Res Part A. 2017;105(5):1457-1468.
  12. Rad MM, Saber-Samandari S, Sadighi M, Tayebi L, Aghdam MM, Khandan A. Macro-and micromechanical modelling of HA-Elastin scaffold fabricated using freeze drying technique. J Nanoanal. 2021.
  13. Al-Sanabani JS, Madfa AA, Al-Sanabani FA. Application of calcium phosphate materials in dentistry. Int J Biomater. 2013;2013(1):876132.
  14. Dorozhkin SV, Epple M. Biological and medical significance of calcium phosphates. Angew Chem Int Ed. 2002;41(17):3130-3146.
  15. Ching SH, Bansal N, Bhandari B. Alginate gel particles–A review of production techniques and physical properties. Crit Rev Food Sci Nutr. 2017;57(6):1133-1152.
  16. Potiwiput S, Tan H, Yuan G, Li S, Zhou T, Li J, Jia Y, Xiong D, Hu X, Ling Z, Chen Y. Dual-crosslinked alginate/carboxymethyl chitosan hydrogel containing in situ synthesized calcium phosphate particles for drug delivery application. Mater Chem Phys. 2020;241:122354.
  17. Kengla C, Kidiyoor A, Murphy SV. Bioprinting complex 3D tissue and organs. In Kidney Transplantation, Bioengineering and Regeneration. Academic Press. 2017; 957-971.
  18. Ananth KP, Jayram ND. A comprehensive review of 3D printing techniques for biomaterial-based scaffold fabrication in bone tissue engineering. Ann 3D Printed Med. 2024;13:100141.
  19. Zhao X, Li N, Zhang Z, Hong J, Zhang X, Hao Y, Wang J, Xie Q, Zhang Y, Li H, Liu M. Beyond hype: unveiling the Real challenges in clinical translation of 3D printed bone scaffolds and the fresh prospects of bioprinted organoids. J Nanobiotechnol. 2024;22(1):500.
  20. Golzar H, Mohammadrezaei D, Yadegari A, Rasoulianboroujeni M, Hashemi M, Omidi M, Yazdian F, Shalbaf M, Tayebi L. Incorporation of functionalized reduced graphene oxide/magnesium nanohybrid to enhance the osteoinductivity capability of 3D printed calcium phosphate-based scaffolds. Compos Part B Eng. 2020;185:107749.
  21. Unagolla JM, Jayasuriya AC. Enhanced cell functions on graphene oxide incorporated 3D printed polycaprolactone scaffolds. Mater Sci Eng C. 2019;102:1-1.
  22. Sharma A, Gupta S, Sampathkumar TS, Verma RS. Modified graphene oxide nanoplates reinforced 3D printed multifunctional scaffold for bone tissue engineering. Biomat Adv. 2022;134:112587.
  23. Iranmanesh P, Torabinejad M, Saatchi M, Toghraie D, Razavi SM, Khademi A. Effect of duration of root canal infection on the ability of dentin-pulp complex regeneration of immature permanent teeth: an animal study. J Endod. 2022;48(10):1301-1307.
  24. Iranmanesh P, Gowdini M, Khademi A, Dehghani M, Latifi M, Alsaadi N, Hemati M, Mohammadi R, Saber-Samandari S, Toghraie D, Khan A. Bioprinting of three-dimensional scaffold based on alginate-gelatin as soft and hard tissue regeneration. J Mater Res Technol. 2021;14:2853-2864.
  25. Iranmanesh P, Ehsani A, Khademi A, Asefnejad A, Shahriari S, Soleimani M, Ghadiri Nejad M, Saber-Samandari S, Khandan A. Application of 3D bioprinters for dental pulp regeneration and tissue engineering (porous architecture). Transp Porous Med. 2022;142(1):265-293.
  26. Fatalla AA, Arzani S, Veseli E, Khademi A, Khandan A, Fahmy MD, Mirmohammadi H, Hasselgren G, Bang H, Kolahi J, Kelishadi R. Revolutionizing systematic reviews and meta-analyses: the role of artificial intelligence in evidence synthesis. Dent Hypotheses. 2023;14(4):93-94.
  27. Khandan A, Jazayeri H, Fahmy MD, Razavi M. Hydrogels: Types, structure, properties, and applications. Biomed Tissue Eng. 2017;4(27):143-169.
  28. Mashhadi Keshtiban M, Taghvaei H, Noroozi R, Eskandari V, Arif ZU, Bodaghi M, Bardania H, Hadi A. Biological and Mechanical Response of Graphene Oxide Surface‐Treated Polylactic Acid 3D‐Printed Bone Scaffolds: Experimental and Numerical Approaches. Adv Eng Mater. 2024;26(3):2301260.
  29. Wei Y, Pan H, Yang J, Zeng C, Wan W, Chen S. Aligned cryogel fibers incorporated 3D printed scaffold effectively facilitates bone regeneration by enhancing cell recruitment and function. Sci Adv. 2024;10(6):eadk6722.
  30. Geng Y, Liu T, Zhao M, Wei H, Yao X, Zhang Y. Silk fibroin/polyacrylamide-based tough 3D printing scaffold with strain sensing ability and chondrogenic activity. Compos Part B Eng. 2024;271:111173.
  31. Rodriguez G, Dias J, d'Ávila MA, Bártolo P. Influence of hydroxyapatite on extruded 3D scaffolds. Proc Eng. 2013;59:263-269.
  32. Lau D, Jian W, Yu Z, Hui D. Nano-engineering of construction materials using molecular dynamics simulations: Prospects and challenges. Compos Part B Eng. 2018;143:282-291.
  33. Attaeyan A, Shahgholi M, Khandan A. Fabrication and characterization of novel 3D porous Titanium-6Al-4V scaffold for orthopedic application using selective laser melting technique. IJCCE. 2023;21-37.
  34. Nouri A, Rabbath J, Khademi A, Khandan A, Iranmanesh P, Fahmy M. Reconstruction of Pathology Induced Anterior Maxillary Defect: A Case Report. Sci Hypotheses. 2024;1:72-78.
  35. Maghsoudlou MA, Nassireslami E, Saber-Samandari S, Khandan A. Bone regeneration using bio-nanocomposite tissue reinforced with bioactive nanoparticles for femoral defect applications in medicine. Avicenna J Med Biotechnol. 2020;12(2):68.
  36. Jasemi A, Moghadas BK, Khandan A, Saber-Samandari S. A porous calcium-zirconia scaffolds composed of magnetic nanoparticles for bone cancer treatment: Fabrication, characterization and FEM analysis. Ceram Int. 2022;48(1):1314-25.
  37. Gašparovič M, Jungová P, Tomášik J, Mriňáková B, Hirjak D, Timková S, Danišovič Ľ, Janek M, Bača Ľ, Peciar P, Thurzo A. Evolving Strategies and Materials for Scaffold Development in Regenerative Dentistry. Appl Sci. 2024;14(6):2270.
  38. Khademi A, Khandan A, Iranmanesh P, Heydari M. Development of a 3D Bioprinted Alginate-Gelatin Hydrogel Scaffold Loaded with Calcium Phosphates for Dental Pulp Tissue Regeneration. IJCCE. 2024.
  39. Anaya-Sampayo LM, García-Robayo DA, Roa NS, Rodriguez-Lorenzo LM, Martínez-Cardozo C. Platelet-rich fibrin (PRF) modified nano-hydroxyapatite/chitosan/gelatin/alginate scaffolds increase adhesion and viability of human dental pulp stem cells (DPSC) and osteoblasts derived from DPSC. Int J Biol Macromol. 2024;133064.
  40. Amiryaghoubi N, Fathi M, Safary A, Javadzadeh Y, Omidi Y. In situ forming alginate/gelatin hydrogel scaffold through Schiff base reaction embedded with curcumin-loaded chitosan microspheres for bone tissue regeneration. Int J Biol Macromol. 2024;256:128335.

 

Nanomedicine Journal
Volume 13, Issue 1
Winter 2026
Pages 183-195