Modification of xenogenic bone substitute materials--effects on the early healing cascade in vitro

Abstract

Introduction: Initial platelet activation with subsequent cytokine release at the defect site plays a crucial role in tissue integration. The aim of this study was to evaluate the influence of topographic and biomimetic collagen modifications of a xenogenic bone substitute material (BSM) on in vitro platelet activation and cytokine release.

Material and methods: Three types of xenogenic BSM were used. Two BSM with different levels of granularity (large granule BSM [XBSM/L], small granule BSM [XBSM/S]) and a BSM with collagen (XBSM/C). All three samples were incubated with platelet concentrate of four healthy volunteers at room temperature for 15 min. For all groups, highly thrombogenic collagen type 1 served as a reference and an additional preparation with platelet concentrate only (without XBSM) served as control. Platelet count and cytokine release of VEGF, PDGF, TGF-β, and IGF into the supernatant were measured.

Results: Compared with the control group, XBSM/C showed an increase in platelets consumption (mean 41,000 ± 26,000/ml vs. 471,000 ± 38,000/ml), cytokine release of VEGF (mean 46.8 ± 7.2 pg/ml vs. 18.8 ± 2.7 pg/ml), and PDGF (mean 18,350 ± 795 pg/ml vs. 2726 ± 410 pg/ml) but not IGF (194,728 ± 51,608 pg/ml vs. 1,333,911 ± 35,314 pg/ml). There was also an increase in cytokine release of TGF-ß in XBSM/C compared with XBSM/S (77,188 ± 27,413 pg/ml vs. 38,648 ± 13,191 pg/ml), but no such difference when compared with XBSM/L (77,188 ± 27,413 pg/ml vs. 53,309 ± 29,430 pg/ml). XBSM/L showed higher platelets consumption (301,000 ± 45,000 vs. 415,000 ± 98,000) and a higher cytokine release of PDGF (3511 ± 247 pg/ml vs. 3165 ± 78 pg/ml) compared with XBSM/S. There was no distinct difference in the levels of VEGF, TGF-ß, and IGF between XBSM/L and XBSM/S.

Conclusions: Topographic as well as biomimetic modifications of the xenogenic BSM showed an increased platelet activation and cytokine release in vitro. This effect on the intrinsic healing cascade could result in comparable enhanced soft- and hard-tissue regeneration in vivo.

Keywords: biomaterials; bone regeneration; bone substitutes; growth factors; guided tissue regeneration; wound healing.