Preprint / Version 1

Methods to Enhance Mechanical Strength of 3D Printed Chitosan Scaffolds for Jawbone Regeneration

##article.authors##

  • Zaara Travadi Ms

DOI:

https://doi.org/10.58445/rars.1450

Keywords:

Chitosan Scaffolds, Jawbone Regeneration, 3D print

Abstract

Current jaw reconstruction methods using autografts and allografts have limitations such as donor site morbidity, limited bone volume, and immunological rejection. As opposed to surgical methods synthetic biomaterials are used however they often fall short in providing the optimal combination of biocompatibility, mechanical strength, and customizable design required for effective jawbone reconstruction. 3D-printed chitosan scaffolds offer a promising alternative due to their biocompatibility, ease of customization, and potential for improved mechanical strength. This review explores strategies to optimize 3D-printed chitosan scaffolds for jaw reconstruction. We examine ways to increase their mechanical strength without compromising biocompatibility, with a particular emphasis on chemical modifications such as hydroxyapatite (HA) and beta-tricalcium phosphate (β-TCP) cross-linking and chitosan polyelectrolyte complex formation. We also discuss the critical roles that 3D printing processes (FDM and SLA) and intrinsic chitosan qualities (degree of deacetylation) play in making an ink printable. Optimizing 3D printing methods for chitosan-ceramic composites and exploring biocompatible additives to enhance printability are identified as key areas for further research. By addressing these challenges, 3D-printed chitosan scaffolds have the potential to become next-generation biomaterials for jaw reconstruction, revolutionizing the field through precise anatomical adaptation, enhanced osteoconductivity, controlled biodegradation, and the capacity for incorporating bioactive molecules, ultimately leading to accelerated bone regeneration and improved functional and aesthetic outcomes.

References

(1) Prevalence of Cleft Lip & Cleft Palate | National Institute of Dental and Craniofacial Research. https://www.nidcr.nih.gov/research/data-statistics/craniofacial-birth-defects/prevalence (accessed 2024-07-05).

(2) Lalloo, R.; Lucchesi, L. R.; Bisignano, C.; Castle, C. D.; Dingels, Z. V.; Fox, J. T.; Hamilton, E. B.; Liu, Z.; Roberts, N. L. S.; Sylte, D. O.; Alahdab, F.; Alipour, V.; Alsharif, U.; Arabloo, J.; Bagherzadeh, M.; Banach, M.; Bijani, A.; Crowe, C. S.; Daryani, A.; Do, H. P.; Doan, L. P.; Fischer, F.; Gebremeskel, G. G.; Haagsma, J. A.; Haj-Mirzaian, A.; Haj-Mirzaian, A.; Hamidi, S.; Hoang, C. L.; Irvani, S. S. N.; Kasaeian, A.; Khader, Y. S.; Khalilov, R.; Khoja, A. T.; Kiadaliri, A. A.; Majdan, M.; Manaf, N.; Manafi, A.; Massenburg, B. B.; Mohammadian-Hafshejani, A.; Morrison, S. D.; Nguyen, T. H.; Nguyen, S. H.; Nguyen, C. T.; Olagunju, T. O.; Otstavnov, N.; Polinder, S.; Rabiee, N.; Rabiee, M.; Ramezanzadeh, K.; Ranganathan, K.; Rezapour, A.; Safari, S.; Samy, A. M.; Sanchez Riera, L.; Shaikh, M. A.; Tran, B. X.; Vahedi, P.; Vahedian-Azimi, A.; Zhang, Z.-J.; Pigott, D. M.; Hay, S. I.; Mokdad, A. H.; James, S. L. Epidemiology of Facial Fractures: Incidence, Prevalence and Years Lived with Disability Estimates from the Global Burden of Disease 2017 Study. Inj. Prev. 2020, 26 (Suppl 1), i27–i35. https://doi.org/10.1136/injuryprev-2019-043297.

(3) Oral health. https://www.who.int/news-room/fact-sheets/detail/oral-health (accessed 2024-07-05).

(4) Pu, J. J.; Hakim, S. G.; Melville, J. C.; Su, Y.-X. Current Trends in the Reconstruction and Rehabilitation of Jaw Following Ablative Surgery. Cancers 2022, 14 (14), 3308. https://doi.org/10.3390/cancers14143308.

(5) Jaw Surgery Risks - UChicago Medicine. https://www.uchicagomedicine.org/conditions-services/plastic-reconstructive-surgery/jaw-orthognathic-surgery/jaw-orthognathic-surgery-risks (accessed 2024-07-05).

(6) Chitosan - an overview | ScienceDirect Topics. https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/chitosan (accessed 2024-07-05).

(7) Antonia Ressler. Chitosan-Based Biomaterials for Bone Tissue Engineering Applications: A Short Review. Polymers 16. https://doi.org/10.3390/polym14163430.

(8) Essawy, A. A.; El-Nggar, A. M. Chapter 10 - Biocompatible Chitosan in Unique Applications for Tissue Engineering. In Materials for Biomedical Engineering; Grumezescu, V., Grumezescu, A. M., Eds.; Elsevier, 2019; pp 279–308. https://doi.org/10.1016/B978-0-12-818415-8.00010-3.

(9) Raftery, R.; O’Brien, F. J.; Cryan, S.-A. Chitosan for Gene Delivery and Orthopedic Tissue Engineering Applications. Molecules 2013, 18 (5), 5611–5647. https://doi.org/10.3390/molecules18055611.

(10) Ibrahim, H. M.; Zairy, E. M. R. E.-; Ibrahim, H. M.; Zairy, E. M. R. E.-. Chitosan as a Biomaterial — Structure, Properties, and Electrospun Nanofibers; IntechOpen, 2015. https://doi.org/10.5772/61300.

(11) Huang, X.; Lou, Y.; Duan, Y.; Liu, H.; Tian, J.; Shen, Y.; Wei, X. Biomaterial Scaffolds in Maxillofacial Bone Tissue Engineering: A Review of Recent Advances. Bioact. Mater. 2024, 33, 129–156. https://doi.org/10.1016/j.bioactmat.2023.10.031.

(12) Figure 1. Biological, mechanical, and structural requirements for an... ResearchGate. https://www.researchgate.net/figure/Biological-mechanical-and-structural-requirements-for-an-ideal-bone-tissue-engineering_fig1_325710661 (accessed 2024-07-05).

(13) Chen, X. B.; Fazel Anvari-Yazdi, A.; Duan, X.; Zimmerling, A.; Gharraei, R.; Sharma, N. K.; Sweilem, S.; Ning, L. Biomaterials / Bioinks and Extrusion Bioprinting. Bioact. Mater. 2023, 28, 511–536. https://doi.org/10.1016/j.bioactmat.2023.06.006.

(14) Islam, M.; Shahruzzaman, M.; Biswas, S.; Sakib, M. N.; Rashid, T. Chitosan Based Bioactive Materials in Tissue Engineering Applications-A Review. Bioact. Mater. 2020, 5. https://doi.org/10.1016/j.bioactmat.2020.01.012.

(15) Abdian, N.; Etminanfar, M.; Hamishehkar, H.; Sheykholeslami, S. O. R. Incorporating Mesoporous SiO2-HA Particles into Chitosan/Hydroxyapatite Scaffolds: A Comprehensive Evaluation of Bioactivity and Biocompatibility. Int. J. Biol. Macromol. 2024, 260, 129565. https://doi.org/10.1016/j.ijbiomac.2024.129565.

(16) Chacon, E. L.; Bertolo, M. R. V.; de Guzzi Plepis, A. M.; da Conceição Amaro Martins, V.; dos Santos, G. R.; Pinto, C. A. L.; Pelegrine, A. A.; Teixeira, M. L.; Buchaim, D. V.; Nazari, F. M.; Buchaim, R. L.; Sugano, G. T.; da Cunha, M. R. Collagen-Chitosan-Hydroxyapatite Composite Scaffolds for Bone Repair in Ovariectomized Rats. Sci. Rep. 2023, 13 (1), 28. https://doi.org/10.1038/s41598-022-24424-x.

(17) Serfandi, D. N.; Dr. Putu Hadi Setyarini; Dr. Purnami, S. T. Pengaruh Penambahan Chitosan (CS) Dan Hydroxyapatite (HA) Pada Polylactid Acid (PLA) Untuk Aplikasi Biomaterial. master, Universitas Brawijaya, 2023. https://repository.ub.ac.id/id/eprint/201456/ (accessed 2024-07-05).

(18) Soriente, A.; Fasolino, I.; Gomez‐Sánchez, A.; Prokhorov, E.; Buonocore, G. G.; Luna‐Barcenas, G.; Ambrosio, L.; Raucci, M. G. Chitosan/Hydroxyapatite Nanocomposite Scaffolds to Modulate Osteogenic and Inflammatory Response. J. Biomed. Mater. Res. A 2022, 110 (2), 266–272. https://doi.org/10.1002/jbm.a.37283.

(19) Zamora, I.; Alfonso Morales, G.; Castro, J. I.; Ruiz Rojas, L. M.; Valencia-Llano, C. H.; Mina Hernandez, J. H.; Valencia Zapata, M. E.; Grande-Tovar, C. D. Chitosan (CS)/Hydroxyapatite (HA)/Tricalcium Phosphate (β-TCP)-Based Composites as a Potential Material for Pulp Tissue Regeneration. Polymers 2023, 15 (15), 3213. https://doi.org/10.3390/polym15153213.

(20) Improving the Mechanical Resistance of Hydroxyapatite/Chitosan Composite Materials Made of Nanofibers with Crystalline Preferential Orientation - PMC. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268343/ (accessed 2024-07-05).

(21) Mohammadi, Z.; Mesgar, A.; Rasouli-Disfani, F. Reinforcement of Freeze−Dried Chitosan Scaffolds with Multiphasic Calcium Phosphate Short Fibers. J. Mech. Behav. Biomed. Mater. 2016, 61. https://doi.org/10.1016/j.jmbbm.2016.04.022.

(22) Mora Boza, A.; Wlodarczyk-Biegun, M.; del Campo, A.; Vázquez-Lasal, B.; San Roman, J. Chitosan-Based Inks: 3D Printing and Bioprinting Strategies to Improve Shape Fidelity, Mechanical Properties, and Biocompatibility of 3D Scaffolds. Biomecánica 2019, 27. https://doi.org/10.5821/sibb.27.1.9199.

(23) Caicedo, J. C.; Caicedo, H. H.; Ramirez-Malule, H. Structural and Chemical Study of β–Tricalcium Phosphate-Chitosan Coatings. Mater. Chem. Phys. 2020, 240, 122251. https://doi.org/10.1016/j.matchemphys.2019.122251.

(24) Demirtaş, T. T.; Irmak, G.; Gümüşderelioğlu, M. A Bioprintable Form of Chitosan Hydrogel for Bone Tissue Engineering. Biofabrication 2017, 9 (3), 035003. https://doi.org/10.1088/1758-5090/aa7b1d.

(25) Wu, Q.; Therriault, D.; Heuzey, M.-C. Processing and Properties of Chitosan Inks for 3D Printing of Hydrogel Microstructures. ACS Biomater. Sci. Eng. 2018, 4 (7), 2643–2652. https://doi.org/10.1021/acsbiomaterials.8b00415.

(26) Liu, J.; Sun, L.; Xu, W.; Wang, Q.; Yu, S.; Sun, J. Current Advances and Future Perspectives of 3D Printing Natural-Derived Biopolymers. Carbohydr. Polym. 2019, 207, 297–316. https://doi.org/10.1016/j.carbpol.2018.11.077.

(27) Ng, W. L.; Yeong, W. Y.; Win Naing, M. Polyelectrolyte Gelatin-Chitosan Hydrogel Optimized for 3D Bioprinting in Skin Tissue Engineering. Int. J. Bioprinting 2016, 2. https://doi.org/10.18063/IJB.2016.01.009.

(28) Sayyar, S.; Gambhir, S.; Chung, J.; Officer, D. L.; Wallace, G. G. 3D Printable Conducting Hydrogels Containing Chemically Converted Graphene. Nanoscale 2017, 9 (5), 2038–2050. https://doi.org/10.1039/C6NR07516A.

(29) Saraiva, S. M.; Miguel, S. P.; Ribeiro, M. P.; Coutinho, P.; Correia, I. J. Synthesis and Characterization of a Photocrosslinkable Chitosan–Gelatin Hydrogel Aimed for Tissue Regeneration. RSC Adv. 2015, 5 (78), 63478–63488. https://doi.org/10.1039/C5RA10638A.

(30) 3D printing of high-strength chitosan hydrogel scaffolds without any organic solvents - Biomaterials Science (RSC Publishing). https://pubs.rsc.org/en/content/articlelanding/2020/bm/d0bm00896f (accessed 2024-07-05).

(31) Melocchi, A.; Parietti, F.; Loreti, G.; Maroni, A.; Gazzaniga, A.; Zema, L. 3D Printing by Fused Deposition Modeling (FDM) of a Swellable/Erodible Capsular Device for Oral Pulsatile Release of Drugs. J. Drug Deliv. Sci. Technol. 2015, 30. https://doi.org/10.1016/j.jddst.2015.07.016.

(32) Skoog, S.; Goering, P.; Narayan, J. Stereolithography in Tissue Engineering. J. Mater. Sci. Mater. Med. 2013, 25. https://doi.org/10.1007/s10856-013-5107-y.

(33) Tylingo, R.; Kempa, P.; Banach-Kopeć, A.; Mania, S. A Novel Method of Creating Thermoplastic Chitosan Blends to Produce Cell Scaffolds by FDM Additive Manufacturing. Carbohydr. Polym. 2022, 280, 119028. https://doi.org/10.1016/j.carbpol.2021.119028.

(34) Homayoni, H.; Ravandi, S. A. H.; Valizadeh, M. Electrospinning of Chitosan Nanofibers: Processing Optimization. Carbohydr. Polym. 2009, 77 (3), 656–661. https://doi.org/10.1016/j.carbpol.2009.02.008.

(35) Li, W.-J.; Shanti, R.; Tuan, R. Electrospinning Technology for Nanofibrous Scaffolds in Tissue Engineering; 2007. https://doi.org/10.1002/9783527610419.ntls0097.

(36) Qasim, S. B.; Zafar, M. S.; Najeeb, S.; Khurshid, Z.; Shah, A. H.; Husain, S.; Rehman, I. U. Electrospinning of Chitosan-Based Solutions for Tissue Engineering and Regenerative Medicine. Int. J. Mol. Sci. 2018, 19 (2), 407. https://doi.org/10.3390/ijms19020407.

(37) Tomar, G.; Dave, J.; Chandekar, S.; Bhattacharya, N.; Naik, S.; Kulkarni, S.; Math, S.; Desai, K.; Sapkal, N. Advances in Tissue Engineering Approaches for Craniomaxillofacial Bone Reconstruction; 2020. https://doi.org/10.5772/intechopen.94340.

(38) Li, J.; Wu, C.; Chu, P. K.; Gelinsky, M. 3D Printing of Hydrogels: Rational Design Strategies and Emerging Biomedical Applications. Mater. Sci. Eng. R Rep. 2020, 140, 100543. https://doi.org/10.1016/j.mser.2020.100543.

(39) Mondschein, R. J.; Kanitkar, A.; Williams, C. B.; Verbridge, S. S.; Long, T. E. Polymer Structure-Property Requirements for Stereolithographic 3D Printing of Soft Tissue Engineering Scaffolds. Biomaterials 2017, 140, 170–188. https://doi.org/10.1016/j.biomaterials.2017.06.005.

(40) Digital light processing mediated 3D printing of biocomposite bone scaffolds: Physico‐chemical interactions and in‐vitro biocompatibility | Request PDF. https://www.researchgate.net/publication/359976118_Digital_light_processing_mediated_3D_printing_of_biocomposite_bone_scaffolds_Physico-chemical_interactions_and_in-vitro_biocompatibility (accessed 2024-07-22).

(41) Liu, Z.; Liang, H.; Shi, T.; Xie, D.; Chen, R.; Han, X.; Shen, L.; Wang, C.; Tian, Z. Additive Manufacturing of Hydroxyapatite Bone Scaffolds via Digital Light Processing and in Vitro Compatibility. Ceram. Int. 2019, 45. https://doi.org/10.1016/j.ceramint.2019.02.195.

(42) Digital light processing stereolithography of hydroxyapatite scaffolds with bone‐like architecture, permeability, and mechanical properties - Baino - 2022 - Journal of the American Ceramic Society - Wiley Online Library. https://ceramics.onlinelibrary.wiley.com/doi/full/10.1111/jace.17843 (accessed 2024-07-22).

(43) Harini, G.; Bharathi, R.; Sankaranarayanan, A.; Shanmugavadivu, A.; Selvamurugan, N. Nanoceramics-Reinforced Chitosan Scaffolds in Bone Tissue Engineering. Mater. Adv. 2023, 4 (18), 3907–3928. https://doi.org/10.1039/D3MA00422H.

(44) How is finite element analysis (FEA) used to predict scaffold behavior? | 5 Answers from Research papers. SciSpace - Question. https://typeset.io/questions/how-is-finite-element-analysis-fea-used-to-predict-scaffold-415w1bbhgc (accessed 2024-07-22).

(45) Vasiliu, A.-L.; Dinu, M. V.; Zaharia, M. M.; Peptanariu, D.; Mihai, M. In Situ CaCO3 Mineralization Controlled by Carbonate Source within Chitosan-Based Cryogels. Mater. Chem. Phys. 2021, 272, 125025. https://doi.org/10.1016/j.matchemphys.2021.125025.

(46) In Situ Mineralization of Hydroxyapatite on Electrospun Chitosan-Based Nanofibrous Scaffolds | Request PDF. https://www.researchgate.net/publication/5529265_In_Situ_Mineralization_of_Hydroxyapatite_on_Electrospun_Chitosan-Based_Nanofibrous_Scaffolds (accessed 2024-07-22)

Posted

2024-08-10