AffordBoneS · Development of personalized and affordable multi-substituted calcium phosphate based scaffolds for bone augmentation applications

Development of personalized and affordable multi-substituted calcium phosphate based scaffolds for bone augmentation applications

1. Summary of the context and overall objectives of the project According to the World Health Organization (WHO), less than half of the world’s population has access to essential healthcare services, highlighting the need for affordable solutions (1). The AffordBoneS project aimed to address this by developing personalized and affordable scaffolds for bone augmentation procedures. This would allow more people to access these treatments and improve their quality of life. The project focused on creating cost-effective materials for bone augmentation that could be used by a larger population. The solution involved fabricating customizable, biomimetic scaffolds tailored to each patient’s jaw bone defect. The three main research objectives were to produce highly porous, multi-substituted calcium phosphate (mCaP) scaffolds suitable for bone regeneration. Objective 1: Designing, fabrication and characterization of mCaP Scaffolds (2). Objective 2: Biological characterization of mCaP Scaffolds by using human stem cells. Objective 3: Demonstrating personalized mCaP Scaffolds. 2. Introduction In Europe alone, it is estimated that 1.5 million bone augmentation procedures are needed each year (3). These procedures are crucial for dental implants when patients don’t have enough bone to secure the implant. The AffordBoneS project aimed to create affordable and customizable solutions for these procedures using 3D-printed calcium phosphate scaffolds enhanced with beneficial ions.This innovative approach offers several advantages over current methods, such as eliminating the need for artificial growth factors, reducing costs through mass customization, and avoiding the need for a second surgery to remove the scaffold. The project brought together experts from various fields, including material engineers, biologists, and companies, to improve bone regeneration techniques. Large bone defects (greater than 2 cm) cannot heal on their own and require scaffolds to guide and support the regeneration process. However, challenges remain in bone tissue engineering, such as reducing the use of growth factors, minimizing immune responses and scaffold rejection, improving blood vessel formation (vascularization), and enhancing mechanical strength (4).While growth factors are commonly used with calcium phosphate ceramics to promote bone growth, concerns have been raised about their safety, including risks of unwanted bone formation, dosage issues, instability, high costs, and potential long-term side effects (5, 6). A promising alternative is to incorporate key elements found in natural bone, such as strontium (Sr2+), magnesium (Mg2+), sodium (Na+), and zinc (Zn2+), into the scaffolds (7).Preliminary studies have shown that scaffolds containing these ions significantly improve bone regeneration compared to those without (8). Despite these advancements, scalable manufacturing and commercialization of these scaffolds remain challenge. Additive manufacturing (3D printing) offers a solution to these challanges by creating scaffolds with the precise microstructure and mechanical strength needed for effective bone regeneration. References: 1. www.who.int/news/item/13-12-2017-world-bank-and-who-half-the-world-lacks-access-to-essential-health-services-100-million-still-pushed-into-extreme-poverty-because-of-health-expenses 2. A. Ressler et al., Vat photopolymerization of biomimetic bone scaffolds based on Mg, Sr, Zn-substituted hydroxyapatite: Effect of sintering temperature, Ceramics International 50(2024) 27403-27415. https://doi.org/10.1016/j.ceramint.2024.05.038 3. A. Hoornaert and P. Layrolle, 2020: Bone regenerative issues related to bone grafting biomaterials, in Dental Implants and Bone Grafts, Chapter 8, 207-215. https://doi.org/10.1016/B978-0-08-102478-2.00009-X 4. S. Kashte et al., Artificial Bone via Bone Tissue Engineering: Current Scenario and Challenges, Tissue Engineering and Regenerative Medicine 14 (2017) 14 1-4. https://doi.org/10.1007/s13770-016-0001-6 5. S. Bose et al., Understanding of dopant-induced osteogenesis and angiogenesis in calcium phosphate ceramics, Trends in Biotechnology 10 (2013) 594-605. https://doi.org/10.1016/j.tibtech.2013.06.005 6. N. Goonoo and A. Bhaw-Luximon, Mimicking growth factors: role of small molecule scaffold additives in promoting tissue regeneration and repair, RSC Advances, 9 (2019) 18124. https://doi.org/10.1039/C9RA02765C 7. T. Cordonnier et al., Biomimetic Materials for Bone Tissue Engineering – State of the Art and Future Trends, Advanced Engineering Materials, 13 (2011) 5. https://doi.org/10.1002/adem.201080098 8. A. Ressler et al., Osteogenic differentiation of human mesenchymal stem cells on substituted calcium phosphate/chitosan composite scaffold, Carbohydrate Polymers 277 (2022) 118883. https://doi.org/10.1016/j.carbpol.2021.118883

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