Abstract

Implant constructs supporting angiogenesis are favorable for treating critically-sized bone defects, as ingrowth of capillaries towards the center of large defects is often insufficient. Consequently, the insufficient nutritional supply of these regions leads to impaired bone healing. Implants with specially designed angiogenic supporting geometry and functionalized with proangiogenic cytokines can enhance angiogenesis. In this study, Vascular Endothelial Growth Factor (VEGF) and High Mobility Group Box 1 (HMGB1) were used for incorporation into poly-ε-caprolactone (PCL)-coated porous titanium implants. Bioactivity of released factors and influence on angiogenesis of functionalized implants were evaluated using a migration assay and angiogenesis assays. Both implants released angiogenic factors, inducing migration of endothelial cells. Also, VEGF-functionalized PCL-coated titanium implants enhanced angiogenesis in vitro. Both factors were rapidly released in high doses from the implant coating during the first 72 h.

Highlights

  • Angiogenesis plays a major role in healing of critically-sized bone defects [1]

  • There was no significant difference between High Mobility Group Box 1 (HMGB1) and Vascular Endothelial Growth Factor (VEGF) + HMGB1

  • Supernatants from titanium implants functionalized with VEGF and/or HMGB1 showed significantly higher chemotactic attraction for GM7373 compared to the starvation medium or 20%

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Summary

Introduction

Angiogenesis plays a major role in healing of critically-sized bone defects [1]. The importance of blood vessel formation for bone repair and building of a skeleton structure was already described in the 18th century as reviewed by Carano et al [2]. Insufficient blood supply is one of the major reasons for impaired bone healing [4]. Such insufficient blood vessel ingrowth is often seen in large oral and maxillofacial defects, resulting from accidents, bone inflammation, or neoplasia, often leading to a non-union of the bone [5,6,7]. An efficient treatment of those critically sized bone defects requires specially designed and functionalized implants. The gold-standard for treating these defects are autologous

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