Peptide-based biomimetic hydrogels for bone regeneration

A multi-component biomimetic hydrogel scaffolds that will guide the architecture of tissue formation in bone defects.

Regeneration of bone defects is a major clinical challenge worldwide. The main objective is to restore and improve the function of bone tissue by scaffolds, providing a suitable environment for tissue regeneration and repair.  An ideal, predictable, and sustainable scaffold has yet to be found.
We have developed multi-component biomimetic hydrogel scaffolds that will guide the architecture of tissue formation in bone defects. The scaffolds are based on short aromatic peptides, which are known for their ability to form nanofibrous rigid hydrogels with structural similarity to the natural extracellular matrix (ECM). Using a co-assembly approach, we combine two or more peptide hydrogelators to control and tailor the mechanical properties of the resulting hydrogels (Figure 1a). Additionally, the peptides are combined with natural polysaccharides such as hyaluronic acid and alginate to form composite biocompatible hydrogels with thixotropic properties that can be injected in a minimally invasive surgical approach, and 3D printed to form custom-made scaffolds (Figure 1b).

One of the main advantages of the composite peptide-polysaccharide hydrogel scaffolds is their structural similarity to the natural ECM as the peptide and polysaccharide ideally resemble the fibrous proteins and glycosaminoglycans, respectively, the two main macromolecules comprising the ECM (Figure 1c).
Such similarity enables the attachment of progenitor cells from the defect area, their proliferation and subsequent bone tissue formation. By changing the concentrations of the peptide and polysaccharide we can tailor the mechanical properties of the hydrogels. This way, scaffolds composed of layers with varying mechanical properties can be formed and 3D printed to fit different areas and qualities of the bone (Figure 1d, e).
As verified by in vitro and in vivo experimental results, the scaffolds’ topography and surface chemistry promote host mesenchymal stem cells (MSCs) recruitment, proliferation, and osteogenesis leading to superior bone defect repair. By incorporating bone minerals, such as particulate dentin or hydroxyapatite, into the hydrogels, we enhance osteogenesis as the bone minerals serve as nucleation sites. Finally, the multi-component hydrogels can be functionalized by immobilization of biologically active molecules (such as the RGD peptide) on the surface, or by the incorporation of growth factors such as BMPs, improving MSCs recruitment, hence, the osteoinductivity of the scaffolds.
We have recently shown the ability of a peptide/hyaluronic acid hydrogel to serve as a carrier for the sustained-release of curcumin, an anti-inflammatory and anti-oxidant agent. Furthermore, the hydrogel enhanced bone regeneration in a rat calvarial critical-sized defect model.
1. Injectable scaffolds: The hydrogels can be injected to precisely fit an irregularly-shaped bone defect in a minimally invasive approach.
2. 3D printed scaffolds: The hydrogels can be 3D printed to form custom-made personalized tissue engineering scaffolds with varying layers.
3. Delivery of bioactive molecules: By modification of the hydrogel components, growth factors and drugs can be released.

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