# Dual Growth Factor Release From Collagen Based Multilayer Films on Ti‐Surfaces Enhances Periimplant Bone Formation and Angiogenic Activity—An Experimental In‐Vivo Study

**Authors:** Philipp Kauffmann, Susanne Wolfer, Christina Behrens, Pauline Schlosser, Christian Dullin, Uwe Schirmer, Klaus Liefeith, Henning Schliephake

PMC · DOI: 10.1111/clr.70045 · Clinical Oral Implants Research · 2025-09-12

## TL;DR

This study shows that releasing two growth factors together on titanium implants improves bone formation and blood vessel growth around dental implants in pigs.

## Contribution

The novel finding is that simultaneous release of BMP-2 and VEGF165, not either alone, enhances bone formation and implant integration.

## Key findings

- After 13 weeks, only implants with combined BMP-2 and VEGF165 showed increased bone formation and bone-implant contact.
- CD31 expression, a marker of angiogenesis, was significantly enhanced around all growth factor-loaded implants.
- Single growth factor release (BMP-2 or VEGF165) did not significantly improve bone formation after 4 weeks.

## Abstract

The aim of the present study was to assess the effect of dual growth factor release from collagen‐based polyelectrolyte multilayer films (PEMs) on titanium implants on periimplant bone formation and angiogenetic activity in minipig mandibles.

Disc shaped Ti implants (5 × 7 × 1 mm) were coated with polyelectrolyte multilayer films and loaded with rhBMP‐2, rhVEGF165, and a combination of both. Uncoated and unloaded Ti implants served as controls. The implants were inserted press‐fit into 5 mm trephine cavities in minipig mandibles and evaluated after 4 and 13 weeks for bone formation, bone implant contact, and periimplant expression of CD31.

After 4 weeks, there was no significant difference in periimplant bone formation nor bone‐implant contact between the different surface conditions. CD31 expression was significantly increased around PEM coated implants loaded with VEGF and BMP each. After 13 weeks, bone implant contact and bone formation were significantly increased only around PEM coated implants with simultaneous release of BMP‐2 and VEGF165. Expression of CD31 was significantly enhanced around all PEM coated implants loaded with growth factors regardless of the type or combination.

It is concluded that simultaneous release of rhBMP‐2 and rhVEGF165 may be required to achieve significant improvement of periimplant bone formation and bone implant contact. Angiogenesis as reflected by CD31 expression is enhanced by both rhVEGF165 and rhBMP‐2 to a similar extent without an additive effect of simultaneous release.

## Linked entities

- **Proteins:** BMP2 (bone morphogenetic protein 2), PECAM1 (platelet and endothelial cell adhesion molecule 1)

## Full-text entities

- **Genes:** VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, BMP2 (bone morphogenetic protein 2) [NCBI Gene 650] {aka BDA2, BMP2A, SSFSC, SSFSC1}, PECAM1 (platelet and endothelial cell adhesion molecule 1) [NCBI Gene 5175] {aka CD31, CD31/EndoCAM, GPIIA', PECA1, PECAM-1, endoCAM}, BMP1 (bone morphogenetic protein 1) [NCBI Gene 649] {aka OI13, PCOLC, PCP, TLD}
- **Chemicals:** Ti (MESH:D014025), PEM (-)

## Full text

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## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12767558/full.md

## References

66 references — full list in the complete paper: https://tomesphere.com/paper/PMC12767558/full.md

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Source: https://tomesphere.com/paper/PMC12767558