P. Korn

Chondroitin sulfate and sulfated hyaluronan‐containing collagen coatings of titanium implants influence peri‐implant bone formation in a minipig model

An improved osseous integration of dental implants in patients with lower bone quality is of particular interest. The aim of this study was to evaluate the effect of artificial extracellular matrix implant coatings on early bone formation. The coatings contained collagen (coll) in conjunction with either chondroitin sulfate (CS) or sulfated hyaluronan (sHya). Thirty-six screw-type, grit-blasted, and acid-etched titanium implants were inserted in the mandible of 6 minipigs. Three surface states were tested: (1) uncoated control (2) coll/CS (3) coll/sHya. After healing periods of 4 and 8 weeks, bone implant contact (BIC), bone volume density (BVD) as well as osteoid related parameters were measured. After 4 weeks, control implants showed a BIC of 44% which was comparable to coll/CS coated implants (48%) and significantly higher compared to coll/sHya coatings (37%, p = 0.012). This difference leveled out after 8 weeks. No significant differences could be detected for BVD values after 4 weeks and all surfaces showed reduced BVD values after 8 weeks. However, at that time, BVD around both, coll/CS (30%, p = 0.029), and coll/sHya (32%, p = 0.015), coatings was significantly higher compared to controls (22%). The osteoid implant contact (OIC) showed no significant differences after 4 weeks. After 8 weeks OIC for controls was comparable to coll/CS, the latter being significantly higher compared to coll/sHya (0.9% vs. 0.4%, p = 0.012). There were no significant differences in osteoid volume density. In summary, implant surface coatings by the chosen organic components of the extracellular matrix showed a certain potential to influence osseointegration in vivo.

Efficacy of tissue engineered bone grafts containing mesenchymal stromal cells for cleft alveolar osteoplasty in a rat model

UNLABELLED The development of sufficient tissue engineered bone grafts for alveolar cleft osteoplasty could reduce the necessity of autogenous bone grafts and its donor site morbidity. The aim of the study was to evaluate tissue engineered bone grafts in an artificially created bone defect. Bone grafts were created in vitro colonizing a synthetic hydroxyapatite-tricalciumphosphate scaffold (BONITmatrix(®)) with either undifferentiated mesenchymal stromal cells (group 1) or osteogenic differentiated mesenchymal stromal cells (group 2). Cells were multiplied from bone marrow of donor rats. Unmodified scaffolds (group 3) and the tissue engineered bone grafts were inserted into artificial maxillary defects of 54 Lewis rats. In 18 animals the defects remained unfilled (control). After one, three and six weeks the rats were sacrificed. The defect was evaluated radiologically and histologically with regard to the remaining defect volume and diameter. Statistical analysis followed. The bone grafts led to a specific bone formation at the defect margin. No complete reunion of any defect was observed within the healing time. After six weeks, the remaining defect volume was 6.86 ± 3.21 mm(3) (control), 4.08 ± 1.36 mm(3) (group 1), 5.00 ± 0.84 mm(3) (group 2) 5.50 ± 1.05 mm(3) (group 3). The remaining defect diameter measured 2.63 ± 0.52 mm (control), 2.39 ± 0.23 mm (group 1), 2.53 ± 0.22 mm (group 2) and 2.70 ± 0.66 mm (group 3). In all experimental groups the defect volume and diameter decreased over time, which was significant for group 1 (p = 0.014), group 2 (p = 0.025) and group 3 (p = 0.048). The defect volume and width was significantly reduced for bone grafts containing undifferentiated cells compared to control (p = 0.035) or scaffolds only (p = 0.05). CONCLUSION Tissue engineered bone grafts induce a pronounced bone formation in artificial bone defects compared to unfilled controls or scaffolds only.

Bone Formation in a Local Defect around Dental Implants Coated with Extracellular Matrix Components

PURPOSE The coating of implant surfaces with components of the extracellular matrix offers an approach to influence peri-implant bone healing. In this study, bone healing around coated implants is analyzed in a peri-implant defect model. MATERIALS AND METHODS Eight months after extraction of the premolar teeth, six dogs received 48 implants (eight per animal) in the mandible. Implant surfaces were sandblasted and acid-etched, and some were additionally coated with collagen type II and chondroitin sulfate (collagen/CS). On each side of the mandible, implants either had no peri-implant defect (control side) or a vertical defect of 5 mm in depth and 0.5, 1.0, or 2.0 mm in width. Implants healed submerged for 8 weeks. Fluorochrome staining, histology, and histomorphometry were used to analyze implant osseointegration. RESULTS Fluorochrome labels showed an increased mineralization around collagen/CS-coated surfaces at 4 weeks (p = .031). Histomorphometry generally showed lower vertical and horizontal bone apposition with increasing gap size for both surface types. In gapless sites and 0.5-mm gaps, collagen/CS coated implants showed increased bone volume in areas directly adjacent to the implant, in comparison with uncoated implants (p < .05). CONCLUSION The width of the peri-implant gap influences peri-implant bone formation. Complete filling of all gaps by newly formed bone could not be observed around either surface. In proximity to the surface, implant surface coating by collagen/CS positively influenced bone formation.

Bioprinting of mineralized constructs utilizing multichannel plotting of a self-setting calcium phosphate cement and a cell-laden bioink

Due to their characteristic resemblance of the mineral component of bone, calcium phosphates are widely accepted as optimal bone substitute materials. Recent research focused on the development of pasty calcium phosphate cement (CPC) formulations, which can be fabricated into various shapes by low-temperature extrusion-based additive manufacturing, namely 3D plotting. While it could be demonstrated that sensitive substances like growth factors can be integrated in such printed CPC scaffolds without impairment of their biological activity live cells cannot be suspended in CPC as they may not be functional when enclosed in a solid and stiff matrix. In contrast, 3D bioprinting of soft cell-laden hydrogels (bioinks) enables the fabrication of constructs with spatially defined cell distribution, which has the potential to overcome problems of conventional cell seeding techniques-but such objects lack mechanical stability. Herein, we combine 3D plotting of CPC and bioprinting of a cell-laden bioink for the first time. As model bioink, an alginate-methylcellulose blend (alg/mc) was used, previously developed by us. Firstly, a fabrication regime was established, enabling optimal setting of CPC and cell survival inside the bioink. As the cells are exposed to the chemical changes of CPC precursors during setting, we studied the compatibility of the complex system of CPC and cell-laden alg/mc for a combined extrusion process and characterized the cellular behavior of encapsulated human mesenchymal stroma cells within the bioink at the interface and in direct vicinity to the CPC. Furthermore, biphasic scaffolds were mechanically characterized and a model for osteochondral tissue grafts is proposed. The manuscript discusses possible impacts of the CPC setting reaction on cells within the bioink and illustrates the advantages of CPC in bioprinting as alternative to the commonly used thermoplasts for bone tissue engineering.

Assessing agreement between preclinical magnetic resonance imaging and histology: An evaluation of their image qualities and quantitative results

One consequence of demographic change is the increasing demand for biocompatible materials for use in implants and prostheses. This is accompanied by a growing number of experimental animals because the interactions between new biomaterials and its host tissue have to be investigated. To evaluate novel materials and engineered tissues the use of non-destructive imaging modalities have been identified as a strategic priority. This provides the opportunity for studying interactions repeatedly with individual animals, along with the advantages of reduced biological variability and decreased number of laboratory animals. However, histological techniques are still the golden standard in preclinical biomaterial research. The present article demonstrates a detailed method comparison between histology and magnetic resonance imaging. This includes the presentation of their image qualities as well as the detailed statistical analysis for assessing agreement between quantitative measures. Exemplarily, the bony ingrowth of tissue engineered bone substitutes for treatment of a cleft-like maxillary bone defect has been evaluated. By using a graphical concordance analysis the mean difference between MRI results and histomorphometrical measures has been examined. The analysis revealed a slightly but significant bias in the case of the bone volume (biasHisto−MRI:Bone volume=2.40 %, p<0.005) and a clearly significant deviation for the remaining defect width (biasHisto−MRI:Defect width=−6.73 %, p≪0.005). But the study although showed a considerable effect of the analyzed section position to the quantitative result. It could be proven, that the bias of the data sets was less originated due to the imaging modalities, but mainly on the evaluation of different slice positions. The article demonstrated that method comparisons not always need the use of an independent animal study, additionally.

Beurteilung von Knochenregeneration und Transplantateinheilung

Ein Hauptproblem der rekonstruktiven Mund-, KieferundGesichtschirurgie ist fehlender Knochen, z. B. in der Kieferspalte. Hier ist eine Kieferspaltosteoplastik indiziert, um den Zahnbogen zu stabilisieren. Die spaltbenachbarten Zähne können dann eruptieren und kieferorthopädisch bewegt werden. Goldstandard ist die Transplantation von autogenem Knochen, was aber mit Nachteilen in der Spenderregion verbunden ist.Mit demTissue-Engineering eröffnen sichneueMöglichkeitenderEntwicklung eines autogenen Transplantats, das ein Konstrukt aus Zellen auf einem „scaffold“ darstellt. Im Rahmen von tierexperimentellen Studien wird die Eignung von Tissue-Engineering-Transplantaten u. a. amModell zur Kieferspaltosteoplastik untersucht. Der bisherige Standard ist die Beurteilung der Knochenregeneration im Defekt ex vivo anhand von histologischen Präparaten. Ziel der vorgestellten Studie war die Prüfung neuer bildgebender Verfahren hinsichtlich ihrer Eignung zur nichtinvasiven Beurteilung von Knochenregeneration und Transplantateinheilung.