Matthias C. Schulz

Biological functionalization of dental implants with collagen and glycosaminoglycans—A comparative study

Biological implant surface coatings are an emerging technology to increase bone formation. Such an approach is of special interest in anatomical regions like the maxilla. In the present study, we hypothesized that the coating of titanium implants with components of the organic extracellular matrix increases bone formation and implant stability compared to an uncoated reference. The implants were coated using collagen-I with either two different concentrations of chondroitin sulfate (CS) or two differentially sulfated hyaluronans. Implant coatings were characterized biochemically and with atomic force microscopy. Histomorphometry was used to assess bone-implant contact (BIC) and bone-volume density (BVD) after 4 and 8 weeks of submerged healing in the maxilla of 20 minipigs. Further, implant stability was measured by resonance frequency analysis (RFA). Implants containing the lower CS concentration had significantly more BIC, compared to the uncoated reference at both times of interest. No significant increase was measured from week 4 to 8. Differences in BVD and RFA were statistically not significant. A higher concentration of CS and the application of sulfated hyaluronans showed no comparable increase in BIC. This study demonstrates a positive effect of a specific collagen-glycosaminoglycan combination on early bone formation in vivo.

Increased bone formation around coated implants.

AIM We hypothesized that coating threaded, sandblasted acid-etched titanium implants with collagen and chondroitin sulphate (CS) increases bone formation and implant stability, compared with uncoated controls. MATERIALS AND METHODS Three different implant surface conditions were applied: (1) sandblasted acid-etched (control), (2) collagen/chondroitin sulphate (low-dose--CS1), (3) collagen/chondroitin sulphate (high-dose--CS2). Sixty 9.5 mm experimental implants were placed in the mandible of 20 minipigs. Bone-implant contact (BIC) and relative peri-implant bone-volume density (rBVD--relation to bone-volume density of the host bone) were assessed after 1 and 2 months of submerged healing. Implant stability was measured by resonance frequency analysis (RFA). RESULTS After 1 month, coated implants had significantly more BIC compared with controls (CS1: 68%, p<0.0001, CS2: 63%, p=0.009, control: 52%). The rBVD was lower for all surface conditions, compared with the hostbone. After 2 months, BIC increased for all surfaces. No significant differences were measured (CS1: 71%, p=0.016, CS2: 68%, p=0.67, control: 63%). The rBVD was increased for coated implants. RFA values were 71-77 at implantation, 67-73 after 1 month and 74-75 after 2 months. Differences in rBVD and RFA were not statistically significant. CONCLUSIONS Data analysis suggests that collagen/CS has a positive influence on bone formation after 1 month of endosseous healing.

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.

Proteomics and Metabolomics for In Situ Monitoring of Wound Healing

Wound healing of soft tissue and bone defects is a complex process in which cellular differentiation and adaption are regulated by internal and external factors, among them are many different proteins. In contrast to insights into the significance of various single proteins based on model systems, the knowledge about the processes at the actual site of wound healing is still limited. This is caused by a general lack of methods that allow sampling of extracellular factors, metabolites, and proteins in situ. Sampling of wound fluids in combination with proteomics and metabolomics is one of the promising approaches to gain comprehensive and time resolved data on effector molecules. Here, we describe an approach to sample metabolites by microdialysis and to extract proteins simultaneously by adsorption. With this approach it is possible (i) to collect, enrich, and purify proteins for a comprehensive proteome analysis; (ii) to detect more than 600 proteins in different defects including more than 100 secreted proteins, of which many proteins have previously been demonstrated to have diagnostic or predictive power for the wound healing state; and (iii) to combine continuous sampling of cytokines and metabolites and discontinuous sampling of larger proteins to gain complementary information of the same defect.

Autogenous bone and a bovine bone substitute for ridge preservation - preliminary clinical and histologic findings.

BACKGROUND Tooth extractions lead to morphological changes of the alveolar ridge. For oral rehabilitation sufficient bone volume of the alveolar ridge is required. This clinical study compared the ability of Bio-Oss® Collagen to autogenous bone to preserve bone volume after tooth extraction. METHODS A total of 17 patients with 20 extraction sites were examined. After extraction, 10 sockets were each filled with either autogenous bone or Bio-Oss® Collagen and covered with a resorbable membrane. The width of the alveolar ridge was measured postoperatively, and after 4 and 6 months respectively. Prior to implant insertion, a bone biopsy was taken from the grafted sites and evaluated histologically. RESULTS The width of the alveolar ridge in the Bio-Oss® Collagen group decreased about 5.33 ± 6.62% after 4 months and 9.45 ± 10.51% after 6 months. The reduction in the group augmented with autogenous bone was 14.31 ± 21.41% after 4 months and 19.17 ± 8.38% after 6 months. No statistically significant differences were observed. The histological examination showed comparable area fractions of total bone in both groups (Bio-Oss® Collagen: 59.99 ± 24.23%; autogenous bone: 61.55 ± 25.13%; p = 1.0). CONCLUSIONS The present study demonstrated that autogenous bone and Bio-Oss® Collagen are suitable for ridge preservation. However, both techniques could not entirely prevent tissue volume loss.

One vs. two piece customized implants to reconstruct mandibular continuity defects: A preliminary study in pig cadavers

OBJECTIVES The reconstruction of mandibular continuity defects by bridging plates often leads to complications. Customized mandibular implants might be an alternative option. In the present study, the stability at the bone-implant-interface of customized two-piece implants was compared to one-piece implants. METHODS Thirty pig mandibles were randomly divided into three groups. One group (A) was left untreated and served as reference. In groups B and C, a continuity defect was created in the left mandibular side. The defects were reconstructed by customized pure titanium implants, manufactured using the LaserCUSING(®) technology. Group B received a one-piece implant; in group C a two-piece implant was inserted to reconstruct the continuity defect. The bonding strength was examined statically and dynamically under standardized conditions. Digital Image Correlation was used for distortion measurement. Different dynamic measurements were performed for orientation purposes. RESULTS The highest bonding strength was measured for the reference group. The two-piece implant showed an increased bonding strength when compared to the one-piece design. In all pig mandibles treated with individual implants a fracture occurred on the non-operated side. This indicates a high primary stability of the bone-implant-interface. CONCLUSION The two-piece individual mandibular implant manufactured by LaserCUSING(®) technology should be further analyzed in future studies.

Experimental findings on customized mandibular implants in Göttingen minipigs – A pilot study

Reconstructing continuity defects of the mandible is still challenging for surgeons. The currently applied conventional titanium bridging plates have considerable rates of complications. Now, a new technology enables an individual shape-identical creation of a mandibular implant in a form-board design by the method of LaserCUSING using pure titanium. This technology has been successfully performed in previous examinations to individually reconstruct mandibular continuity defects. This pilot study evaluated the surgical procedure in 10 female Göttingen mini pigs. First, a computed tomography scan from a mini pig cranium was performed. A three-dimensional model of the mandible was designed by data conversion. Based on the data, a customized mandibular implant resembling the natural shape was virtually created and manufactured. Then, a continuity defect of the left mandible was created in a standardized way. The implants were inserted into the defect and the wounds were allowed to heal for 21, 35, 56 and 180 days. During the healing period, no signs of inflammation or infection were observed. After the sacrifice of the minipigs the mandibles were resected. Histological microsections using Donaths sawing and grinding technique were manufactured and stained with Masson Goldner trichrome staining. The histomorphological results showed a pronounced ossification at the outer and inner surface of the implants. This animal study describes a promising approach to optimize customized implants for the application in humans.

Evaluation of selected speech parameters after prosthesis supply in patients with maxillary or mandibular defects.

Background: Ablative surgery of oropharyngeal tumors frequently leads to defects in the speech organs, resulting in impairment of speech up to the point of unintelligibility. The aim of the present study was the assessment of selected parameters of speech with and without resection prostheses. Patients and Methods: The speech sounds of 22 patients suffering from maxillary and mandibular defects were recorded using a digital audio tape (DAT) recorder with and without resection prostheses. Evaluation of the resonance and the production of the sounds /s/, /sch/, and /ch/ was performed by 2 experienced speech therapists. Additionally, the patients completed a non-standardized questionnaire containing a linguistic self-assessment. Results: After prosthesis supply, the number of patients with rhinophonia aperta decreased from 7 to 2 while the number of patients with intelligible speech increased from 2 to 20. Correct production of the sounds /s/, /sch/, and /ch/ increased from 2 to 13 patients. A significant improvement of the evaluated parameters could be observed only in patients with maxillary defects. The linguistic self-assessment showed a higher satisfaction in patients with maxillary defects. Conclusion: In patients with maxillary defects due to ablative tumor surgery, an increase in speech performance and intelligibility is possible by supplying resection prostheses.

Contour identical implants to bridge mandibular continuity defects - individually generated by LaserCUSING ® - A feasibility study in animal cadavers

BackgroundAblative tumor surgery often results in continuity defects of the mandible. When an immediate reconstruction using autologous bone grafts is not possible the bridging of the defects with a variety of bridging plates might be achieved. However, those bridging plates have the risk of plate fractures or exposure. Customized titanium implants manufactured using CAD/CAM and the LaserCUSING® technique might be an alternative.MethodsIn the present study, computed tomographies (CT) of porcine cadaver mandibles were generated and transferred into DICOM data. Following, different continuity defects were surgically created in the mandibles. Based on the DICOM data customized titanium implants were manufactured using CAD/CAM procedures and the LaserCUSING® technique. The implants were fixed to the remaining stumps with screws. Subsequently, the accuracy of the reconstructed mandibles was tested using plaster casts.ResultsThe workflow from the CT to the application of the customized implants was proved to be practicable. Furthermore, a stable fixation of the customized implant to the remaining stumps could be achieved. The control of the accuracy showed no frictions or obstacles.ConclusionThe customized titanium implant seems to be a promising approach to bridge continuity defects of the mandible whenever an immediate reconstruction with autologous bone is not possible.