Spongostan™ Leads to Increased Regeneration of a Rat Calvarial Critical Size Defect Compared to NanoBone® and Actifuse.

Richard Stange,Barbara Kaltschmidt,Christian Kaltschmidt,Thomas Vordemvenne,Madlen Merten,Johannes F W Greiner,Dirk Wähnert,Julian Koettnitz,Daniel Kronenberg

doi:10.3390/ma14081961

Abstract

Bone substitute materials are becoming increasingly important in oral and maxillofacial surgery. Reconstruction of critical size bone defects is still challenging for surgeons. Here, we compared the clinically applied organic bone substitute materials NanoBone® (nanocrystalline hydroxyapatite and nanostructured silica gel; n = 5) and Actifuse (calcium phosphate with silicate substitution; n = 5) with natural collagen-based Spongostan™ (hardened pork gelatin containing formalin and lauryl alcohol; n = 5) in bilateral rat critical-size defects (5 mm diameter). On topological level, NanoBone is known to harbour nanopores of about 20 nm diameter, while Actifuse comprises micropores of 200–500 µm. Spongostan™, which is clinically applied as a haemostatic agent, combines in its wet form both nano- and microporous topological features by comprising 60.66 ± 24.48 μm micropores accompanied by nanopores of 32.97 ± 1.41 nm diameter. Micro-computed tomography (µCT) used for evaluation 30 days after surgery revealed a significant increase in bone volume by all three bone substitute materials in comparison to the untreated controls. Clearly visual was the closure of trepanation in all treated groups, but granular appearance of NanoBone® and Actifuse with less closure at the margins of the burr holes. In contrast, transplantion of Spongostan™ lead to complete filling of the burr hole with the highest bone volume of 7.98 ccm and the highest bone mineral density compared to all other groups. In summary, transplantation of Spongostan™ resulted in increased regeneration of a rat calvarial critical size defect compared to NanoBone and Actifuse, suggesting the distinct nano- and microtopography of wet Spongostan™ to account for this superior regenerative capacity. Since Spongostan™ is a clinically approved product used primarily for haemostasis, it may represent an interesting alternative in the reconstruction of defects in the maxillary region.

Highlights

Bone healing and implant integration are highly regulated processes that are based on optimal conditions, both biological and mechanical
Beyond the applicability of SpongostanTM as a stem cell or growth factor carrier for bone recovery [19,20], we demonstrated the sole presence of micro- and nanotopographical cues on SpongostanTM to be sufficient for functional regeneration of a critical-size calvarial rat bone defect [14]
We compared the in vivo bone regeneration potential of the two clinical proven synthetic bone substitute materials NanoBone® and Actifuse with

Summary

Introduction

Bone healing and implant integration are highly regulated processes that are based on optimal conditions, both biological and mechanical. Impaired bone healing and implant integration are still a major challenge in dental surgery [1,2,3]. Autologous bone grafting is still the “gold standard” since it combines all requirements for ideal bone substitute materials: biocompatibility, bioresorbabilty, osteoconductivity, osteoinductivity as well as structural and mechanical similarity to bone [6]. In dental surgery problems arise when alveolar ridge augmentation is needed due to the limited bone volume in the jaw. In this context guided bone regeneration is the most used technique. Current bone substitutes for implant dentistry provide only osteoconduction but not osteoinduction [7]. A promising further strategy might involve the use of mesenchymal stem cells (MCS) [8]

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