Einfluss der differenzierten Präsentation multipler Wachstumsfaktoren in biomimetischen Multilayerbeschichtungen von Titanimplantaten auf die Angiogenese und Osteogenese

Influence of the differentiated presentation of multiple growth factors in biomimetic multilayer coatings of titanium implants on angiogenesis and osteogenesis

by Pauline Schlosser
Doctoral thesis
Date of Examination:2025-07-07
Date of issue:2025-05-16
Advisor:Prof. Dr. Dr. Philipp Kauffmann
Referee:Prof. Dr. Dr. Philipp Kauffmann
Referee:Prof. Dr. Arndt Schilling
Persistent Address: http://dx.doi.org/10.53846/goediss-11275

 

 

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Abstract

English

The aim of the present study was to test the simultaneous and sequential release of the growth factors rhVEGF165 and rhBMP2 from poly-L-lysine-heparin (PLL-Hep) and poly-L-lysine-heparin-collagen (PLL-Hep-Col) poly-electrolyte multilayer (PEM) coating on titanium surfaces to increase the implant-bone-contact and to enhance the peri-implant bone formation to enable improved osseointegration, particularly in patients with systemic diseases such as osteoporosis, diabetes mellitus and trauma. For this purpose, titanium implants were first loaded with PEM and growth factors and then implanted press-fit into trephine cavities in the lower border of the mandibles of minipigs for an observation period of 4 and 13 weeks. In the histological preparations according to Smith Karagianes, there were no significant differences between the coated and uncoated implants after 4 weeks. After 13 weeks the simultaneous growth factor coating in the PEM showed significantly higher implant-bone contact and significantly increased new bone formation. The influence was mainly limited to the area of 100 µm around the implant. As the distance to the implant increased, the influence of the coatings decreased. In contrast to previous findings, primary BMP2 release with subsequent VEGF release also showed increased bone growth in addition to simultaneous growth factor release. This sequence of growth factor exposure is contrary to the current view of the temporal patterns of growth factor release. Additionally, the combined growth factor release showed a synergistic effect, with BMP2 singularly having a greater impact than VEGF. The greatest proportion of newly formed bone and the greatest implant-bone contact after 13 weeks was present in the PLL-Hep-Col coating with simultaneous growth factor release.
Keywords: heparin poly-electrolyte multilayer; bone morphogenic proteins; vascular endothelial growth factor; controlled release