Multifunctional Personalized Self-Assembled Biomaterials for Bone Regeneration

Project Information

PersonalBone

Grant agreement ID: 948102

DOI

10.3030/948102

EC signature date 18 November 2020

Start date 1 January 2021

End date 31 December 2026

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 499 375,00

EU contribution

€ 1 499 375,00

Coordinated by

TEL AVIV UNIVERSITY
Israel

Periodic Reporting for period 3 - PersonalBone (Multifunctional Personalized Self-Assembled Biomaterials for Bone Regeneration)

Reporting period: 2024-01-01 to 2025-06-30

Summary of the context and overall objectives of the project

Autologous bone grafting is currently the clinical gold standard for the repair of large bone defects resulting from non-union fractures, bone loss due to tumor resection, metabolic bone diseases, and other pathologies. Approximately 2.2 million bone graft procedures are annually performed worldwide, including 1 million procedures in Europe alone. However, this clinical approach entails several key disadvantages, including severe pain and morbidity due to healthy bone harvest, the limited amount of available bone, and an unpredictable replacement rate.
The main goal of the PersonalBone project is to develop a new patient-specific scaffold for in-situ bone tissue regeneration. For this purpose, novel biocompatible materials will be fabricated by employing a straight-forward molecular self-assembly approach. The materials will be designed to be used as 3D-printing bioinks, allowing to fabricate personalized scaffolds. The newly-developed materials will be thoroughly characterized and tested both in vitro and in vivo using animal models.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

1. Rational design and development of multifunctional stimulatory hydrogels for bone tissue regeneration: To set the basis for the development of multifunctional hydrogels, we have expanded our peptide-based hydrogel library. We designed various peptide building blocks by different approaches, including rational sequence engineering of a collagen-derived tripeptide, backbone modification, and co-assembly with various components such as polysaccharides. These diverse building blocks allowed us to fabricate hydrogels of different and improved physical properties.
2. 3D printing of layered hydrogel scaffolds based on CT computer-assisted design: In spite of numerous advantageous properties, many peptide-based hydrogels are non-injectable, a key requirement for the fabrication of 3D bioinks. To convey printability properties to a non-injectable dipeptide-based hydrogel, we modified the peptide via chemical conjugation. Co-assembly with gelatin allowed us to fabricate a composite printable hydrogel without the need for any potentially harmful post-printing crosslinking processes.
3. Complete in-vitro analysis of the fabricated scaffolds: Aiming to screen the newly-designed peptide-based hydrogels for potential use as tissue regeneration scaffolds, we utilized various cell culture assays, allowing to assess cells proliferation and differentiation. We could show the growth and differentiation of pre-osteoblast cells on our newly-designed scaffolds. Moreover, our 3D-printed peptide-based hydrogels could support the growth of murine fibroblasts and stem cells.
4. Explore bone regeneration by the designed scaffolds using in-vivo models: Aiming to demonstrate the utilization of our hydrogels in vivo, a polysaccharide-incorporated peptide-based hydrogel was implanted in critical-sized bone defects in rats. In contrast to control treatments, the hydrogel treatment resulted in almost complete bone restoration and an immunomodulatory effect.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Within the scope of the PersonalBone project, we were recently able to show approximately 93% bone restoration of critical-sized bone defects in rats following the implantation of a polysaccharide-peptide composite hydrogel. In contrast to control state-of-the-art treatments, the hydrogel-treated defects showed an induction of bone deposition not only around the margins of the defect, but also in the middle parts. Modulation of the immune response was also observed in the hydrogel-treated animals, as indicated by the increase of regeneration-promoting macrophages along with the decrease of inflammatory macrophages. Unexpectedly, the regeneration and immunomodulation effects were observed upon the implantation of a hydrogel composed of a peptide and polysaccharide only, without the addition of any other additives.
Aiming to fabricate a personalized bone regeneration scaffold, we plan to 3D print layered architectures constructed of hydrogel of different physical properties which will mimic the multi-layer structure of the natural bone. This will further allow us to generate scaffolds based on cone beam computed tomography (CBCT) imaging of specific detects induced in model animals, thereby establishing a model for the future design of patient-specific bone regeneration scaffolds.