Cornelia Katharina Mueller

Radiation-induced microenvironments - The molecular basis for free flap complications in the pre-irradiated field?

BACKGROUND AND PURPOSE The effect of preoperative radio- or radiochemotherapy on the survival of free flaps used for head and neck reconstruction is reported in a contradictory way. Although there is a lot of knowledge on radiation-induced wound healing disorders from animal models there are no investigations on human patients so far. Our prospective study aimed at clarifying the effect of radiotherapy on clinically apparent free flap complications and on correlating them with radiation-induced extracellular matrix (ECM) remodeling. MATERIALS AND METHODS Healing of 114 free flaps was monitored in a prospective study and correlated with different anamnestic features, such as diabetes and radio- or radiochemotherapy using multivariate regression. During the operation connective tissue biopsies were harvested from the graft beds and analyzed for Transforming Growth Factor (TGF)-beta(1)-expression by means of Western blotting as well as Tissue Inhibitor of Matrix-Metallo-Proteinase (TIMP)-1 and Matrix-Metallo-Proteinase (MMP)-1 by immunohistochemistry. RESULTS History of radio- or radiochemotherapy was the only factor significantly predicting free flap complications. Radiochemotherapy resulted in a significant increase in TGF-beta(1)- and TIMP-1-expression, while MMP-1-expression was not significantly altered. Radiotherapy alone significantly increased TIMP-1-expression without detectable effects on TGF-beta(1) and MMP-1. CONCLUSIONS Radio- and radiochemotherapy alter graft bed ECM organization prior to surgery. This alteration impacts significantly on free flap survival in the pre-irradiated field.

Comparative analysis of osseointegration of titanium implants with acid-etched surfaces and different biomolecular coatings

OBJECTIVES An increasing trend toward implantation in complex cases, as well as early loading, is beginning to emerge in dental implantology. Long-term stability of the inserted implants greatly depends on the osseointegration process. Although there are numerous current research efforts aimed at functionalizing implant surfaces, no single factor has proved to be beneficial for osseointegration. The aim of the present study was to investigate whether a combination coating of collagen I and different cytokines enhances osseointegration. STUDY DESIGN Commercially available titanium implants (Semados S; Bego Implant Systems, Bremen, Germany) were coated with collagen I and either 1 μg or 10 μg of bone morphogenic protein 2, vascular endothelial growth factor 165, basic fibroblast growth factor 2, or a combination of all 3 factors by using the biodot method. Experimental implants (1 pure titanium, 1 collagen I coated and 8 different cytokine coatings) were inserted in the frontal skulls of 9 domestic pigs (10 implants in each animal). Implants were retrieved 2, 4, and 8 weeks after surgery. Samples were subjected to microradiography and immunohistochemistry for collagen I and osteocalcin. RESULTS Implant coating with collagen I significantly increased collagen I (P = .028) and osteocalcin (P = .037) expression at the 2-week follow-up and osteocalcin expression (P = .042) as well as the bone implant contact (P = .049) at the 4-week follow-up compared with pure titanium. Additional cytokine coating had no significant effect compared with the collagen I coating. CONCLUSIONS It can be concluded that collagen I coating enhances osseointegration. However, additional growth factor application has no further beneficial effects.

Angiogenic gene-modified fibroblasts for induction of localized angiogenesis.

BACKGROUND Induction of localized angiogenesis is of particular interest in the field of plastic surgery. Topical application of recombined vascular endothelial growth factor (VEGF) shows only little effect on graft healing. This study describes the establishment of an ex vivo engineered VEGF slow release system based on autogenous fibroblasts. METHODS Primary fibroblasts were subjected to nucleofection and analyzed for transgene expression 1, 2, 3, 4, 7, and 9 d post-nucleofection using FACS. VEGF transgene expression was measured in cell culture supernatants using ELISA. Transgenic protein functionality was examined in the HUVEC proliferation assay. The effect of VEGF transgene expression on the neovascularization of a collagen membrane was investigated in a rat model. RESULTS Primary fibroblasts were nucleofected with an efficiency of 63.331% and transgene expression showed persistence up to day 9 post-nucleofection. VEGF was expressed in the cell culture up to day 14 with an expression peak at day 3. The cytokine was functionally active. VEGF transgene was released in vivo at day 7 and enhanced neovascularization of a collagen membrane. CONCLUSIONS Nucleofection is the ideal nonviral tool to engineer transgenic primary fibroblasts for transplantation purpose in an ex vivo gene therapeutic approach. Such ex vivo gene therapy is safe and efficient. Its suitability should be further evaluated in more complex flap models, for example the transfer of a free myocutaneous gracilis flap in the pre-irradiated neck region.

Scalp defect repair: a comparative analysis of different surgical techniques.

AbstractScalp defects often arise in multimorbid patients. This study aimed at establishing an algorithm of defect repair with particular focus on new regenerative options.All patients, who consulted to the Department of Oral and Maxillofacial Surgery/Plastic Surgery, University Jena between April 2005 and March 2010 were reviewed. Different reconstructive options were compared with regard to duration of hospital stay as well as rate of reoperations needed to achieve full closure.Sixty-eight patients were identified. Local flaps were more effective than skin grafts (P = 0.038) and microvascular free flaps (P = 0.037) in case of skin-galea-periosteal-defects. However, no differences were found between skin grafting in combination with wound bed preconditioning using a dermal regeneration template and microvascular free flap transfer.Scalp defects should be repaired based on careful evaluation of defect anatomy as well as patient’s general health. Application of dermal regeneration templates allows for an increase of the indication spectrum of free skin grafts.

Influence of insertion protocol and implant shoulder design on inflammatory infiltration and gene expression in peri-implant soft tissue during nonsubmerged dental implant healing

OBJECTIVE This study aimed at elucidating the influence of insertion protocol and implant shoulder design on peri-implant soft tissue healing. STUDY DESIGN One month after removal of all maxillary premolars in 12 minipigs, 4 implants were installed in each quadrant. According to implant shoulder design, 3 groups were established: 1) rough, 0.4 mm; 2) smooth, 3 mm; and 3) smooth, 0.4 mm. One quadrant was randomized to flapless insertion, and the other was used for flap surgery in each animal. Mucosa biopsies were retrieved 1, 2, 4, and 12 weeks after surgery and subjected to a leukocyte count as well as pangenomic gene expression analysis. RESULTS Flapless surgery shortened the period of postsurgical inflammation as shown by the leukocyte count and induced early constructive remodeling as indicated by the microarray. Regarding design of the implant shoulder, leukocyte count values were lowest for group 3. CONCLUSION Flapless surgery in combination with group 3 implants appears to enhance peri-implant soft tissue healing.

Correlation between clinical findings and CT-measured displacement in patients with fractures of the zygomaticomaxillary complex.

BACKGROUND This prospective clinical study aimed to analyse the influence of displacement on duration and severity of symptoms of fractures of the zygomaticomaxillary complex. METHODS 47 patients, who received surgical treatment of zygomaticomaxillary complex fractures at the Department of Oral and Maxillofacial Surgery/Plastic Surgery, University Hospital Jena were examined preoperatively, 1, 3 and 10 days as well as 6 months post-operation for ophthalmologic, occlusal and neurosensory changes. RESULTS Preoperatively, periorbital haematoma and ooedema were present in 76.6% and 31.9% of the patients, which increased until day 1 post-op and decreased until the end of hospital stay. Preoperative diplopia was present in 83.0% of the patients and resolved postoperatively in all but 3 cases, in whom it persisted until end of the study. Occlusal disturbances and limited mouth opening were present in 21.3% of the patients and resolved by end of the study in all but 2 cases. Neither ophthalmologic nor occlusal changes correlated with the degree of displacement. Postoperatively no significant differences were detectable among the groups. In 44.8% of the patients neurosensory disturbances persisted until end of the follow-up. In the non-displaced fracture group none of the patients suffered from neurosensory disturbances at the 6-month follow-up. CONCLUSION Although the degree of displacement has a significant impact on the incidence of sensory disturbances preoperatively, postoperatively no differences were observed between displaced and non-displaced fractures.

Multivariate analysis of the influence of patient-, tumor-, and management-related factors on the outcome of surgical therapy for facial basal-cell carcinoma.

PurposeThis retrospective, case-control study aimed at evaluating the influence of patient-, tumor-, and management-related factors on the outcome of surgical therapy for facial basal-cell carcinoma (BCC) employing a multivariate analysis.MethodsOne hundred one patients who underwent ablative surgery for BCC of the face at the Department of Oral and Maxillofacial Surgery/ Plastic Surgery, University Hospital Jena, between April 2005 and January 2009, were analyzed. Patients’ charts were screened for anamnestic features as well as management- and follow-up-related details. Standardized photographs were subjected to an esthetic evaluation. Logistic regression was used to identify factors associated with postsurgical wound healing disorders, recurrence, and esthetic impairment.ResultsFollowing surgical BCC treatment, age and tumor location in the area of the eyes, nose, lips, and ears were independent predictors of wound healing disorders. Tumor location in the area of the eyes, nose, lips, and ears, subtype and class were independent predictors of recurrence. Female gender and location in the area of the eyes, nose, lips, and ears were independent predictors of esthetic impairment. Micrographic surgery and distant reconstruction technique were management-related predictors of wound healing disorders and esthetic outcome, respectively.ConclusionsThe identified negative predictors of treatment outcome should be included in the informed consent to objectify the patients preoperative expectations.

Analysis of the influence of the macro- and microstructure of dental zirconium implants on osseointegration: a minipig study

OBJECTIVES It was the aim of this study to analyze the influence of implant design and surface topography on the osseointegration of dental zirconium implants. STUDY DESIGN Six different implant designs were tested in the study. Nine or 10 test implants were inserted in the frontal skull in each of 10 miniature pigs. Biopsies were harvested after 2 and 4 months and subjected to microradiography. RESULTS No significant differences between titanium and zirconium were found regarding the microradiographically detected bone-implant contact (BIC). Cylindric zirconium implants showed a higher BIC at the 2-month follow-up than conic zirconium implants. Among zirconium implants, those with an intermediate Ra value showed a significantly higher BIC compared with low and high Ra implants 4 months after surgery. CONCLUSIONS Regarding osseointegration, titanium and zirconium showed equal properties. Cylindric implant design and intermediate surface roughness seemed to enhance osseointegration.

Microvascular free flaps for mandibular reconstruction in Goldenhar syndrome.

Although Goldenhar syndrome is a relatively common craniofacial malformation, there is some debate regarding the ideal treatment of severe mandibular hypoplasia. Traditionally, patients with severe mandibular deficits have been treated with iliac or costochondral bone grafts followed by distraction osteogenesis, with mixed results. The authors present their experience with the use of the osteocutaneous fibula and scapula free flap for mandibular reconstruction in patients with severe mandibular hypoplasia. The cases of 4 patients who underwent free-flap reconstruction of a severely hypoplastic mandible due to Goldenhar syndrome are presented. Microvascular reconstruction of the severely hypoplastic mandible is possible with the osteocutaneous scapula and the fibula flap. Minimal donor-site morbidity is elicited. Furthermore, the vertical relationship can be restored adequately, and breathing is facilitated. The microvascular fibula and scapula flap are a viable option for reconstruction of the severely hypoplastic mandible in patients with Goldenhar syndrome.

Late changes in cutaneous gene expression patterns after adjuvant treatment of oral squamous cell carcinoma (OSCC) by radiation therapy

OBJECTIVE The objective of this study was to investigate radiation-induced late changes in cutaneous gene expression using a microarray platform and quantitative, real-time, reverse-transcriptase polymerase chain reaction (RT-PCR) validation. STUDY DESIGN Paired irradiated and nonirradiated skin biopsies were obtained from 19 patients with a history of oral squamous cell carcinoma (OSCC) treated by surgery and adjuvant radiotherapy at the time of secondary corrective surgery. Topic-defined PIQOR (Parallel Identification and Quantification of RNAs) skin microarrays were used to compare gene expression profiles between control and irradiated skin sample in 8 patients. The data were validated for matrixmetalloproteinase (MMP)-1 and tissue-inhibitor of matrixmetalloproteinase (TIMP)-1 by RT-PCR for all patients. RESULTS Irradiation markedly enhanced the expression of molecules associated with the transforming growth factor (TGF)-beta(1) signaling pathway, blood vessel development, as well as extracellular matrix constitution and turn-over. CONCLUSIONS Our data suggest that radiation-induced late changes in cutaneous gene expression mainly affect molecules related to extracellular matrix (ECM)-constitution and-remodeling.