# 3D‐Printed Titanium Implants with Bioactive Peptide‐Polysaccharide Scaffolds for Personalized Bone Reconstruction

## TL;DR

3D-printed titanium implants are made more effective for bone repair by integrating a bioactive scaffold that promotes better bone growth.

## Contribution

A cell-free, growth-factor-free strategy using a peptide-hyaluronic acid scaffold improves bone integration in 3D-printed titanium implants.

## Key findings

- Scaffold-integrated implants significantly outperformed inert controls in a rabbit bone defect model.
- Hydrogel integration nearly doubled inner bone volume and improved trabecular architecture.
- Histological analysis showed enhanced bone-implant integration and reduced inflammation.

## Abstract

Large bone defects caused by trauma, tumor resection, or congenital abnormalities remain a major clinical challenge. Standard titanium implants are widely used due to their strength and biocompatibility, but their bioinert surfaces often lead to poor osseointegration. The emergence of 3D printing has enabled patient‐specific titanium implants with tailored architecture and mechanical properties. However, these constructs still lack the bioactivity required for robust and spatially uniform bone integration, particularly within the implant core. To address this limitation, we developed a bioactive, cell‐free strategy that integrates porous titanium implants with a nanofibrillar peptide‐hyaluronic acid scaffold, delivered either as a hydrogel or in lyophilized form. The scaffold exhibited enhanced enzymatic stability and supported osteoblast‐like cell adhesion in vitro. In a rabbit calvarial critical‐size bone defect model, scaffold‐integrated implants significantly outperformed inert controls, with hydrogel integration nearly doubling inner bone volume and improving trabecular architecture. Histological analysis confirmed enhanced bone‐implant integration, active periosteum, healthy marrow, and reduced inflammation. This acellular, growth‐factor‐free approach combines the structural precision of titanium with the regenerative potential of ECM‐mimicking scaffolds, offering a translatable pathway for personalized skeletal repair.

Porous 3D‐printed titanium implants are made bioactive by integration with a supramolecular peptide‐hyaluronic acid nanofibrillar scaffold, without the addition of exogenous cells or growth factors. Uniform filling of the implant architecture promotes vascularized, spatially homogeneous bone regeneration, significantly enhancing osteogenesis throughout the implant, including its core, in a critical‐size bone defect model.