Antoine J.W.P. Rosenberg

Gelatin-Methacryloyl Hydrogels: Towards Biofabrication-Based Tissue Repair.

Research over the past decade on the cell-biomaterial interface has shifted to the third dimension. Besides mimicking the native extracellular environment by 3D cell culture, hydrogels offer the possibility to generate well-defined 3D biofabricated tissue analogs. In this context, gelatin-methacryloyl (gelMA) hydrogels have recently gained increased attention. This interest is sparked by the combination of the inherent bioactivity of gelatin and the physicochemical tailorability of photo-crosslinkable hydrogels. GelMA is a versatile matrix that can be used to engineer tissue analogs ranging from vasculature to cartilage and bone. Convergence of biological and biofabrication approaches is necessary to progress from merely proving cell functionality or construct shape fidelity towards regenerating tissues. GelMA has a critical pioneering role in this process and could be used to accelerate the development of clinically relevant applications.

Free Vascularized Flaps for Reconstruction of the Mandible: Complications, Success, and Dental Rehabilitation

PURPOSE To evaluate complications and success of mandibular reconstruction with free fibula flaps, iliac crest flaps, and forearm flaps with reconstruction plates and to evaluate dental rehabilitation after these reconstructions. PATIENTS AND METHODS Eighty-three patients with segmental mandibular defects were included. Correlation analyses were used to determine the relationship between reconstruction type and clinical parameters with recipient-site complications and success. The dental rehabilitation was evaluated in successfully reconstructed survivors. RESULTS Multivariate analyses showed significant correlations between flap type and success (P < .0001). Of the patients, 51 (61%) were alive 2 years after the reconstruction. Mandibular reconstruction with a free forearm flap and reconstruction plate was associated with higher complication rates at the recipient site and higher failure rates compared with reconstruction with free vascularized bone flaps. Of the 32 successfully reconstructed survivors, 14 (44%) had a complete dental rehabilitation, of which 10 had dental implants and 4 did not. Only 6 (29%) of the edentulous survivors ultimately had an implant-supported prosthesis. CONCLUSIONS Reconstruction of the mandible with a free vascularized bone flap is superior to reconstruction with a free forearm flap with a reconstruction plate. Complete dental rehabilitation was reached in fewer than half of the surviving patients.

A prospective study on prognostic factors for free-flap reconstructions of head and neck defects

The purpose of this study is to examine a cohort of patients with free-flap reconstruction prospectively and to identify the prognostic factors for postoperative medical and surgical complications. All 150 patients required a free-flap reconstruction after ablative surgery for a defect in the head and neck area. Medical complications and major surgical complications were correlated with patient factors. An ASA score of 3 and male gender were statistically significant prognostic factors for medical complications. The ASA scoring system is a slightly better prognostic factor for medical complications than Charlson comorbidity stage on forward logistic regression analysis. Female gender and an operation time exceeding 10h were statistically significant prognostic factors for major surgical complications.

The effect of alar cinch sutures and V-Y closure on soft tissue dynamics after Le Fort I intrusion osteotomies

UNLABELLED Adverse effects on the soft tissues after Le Fort I osteotomies include: broadening of the alar base, loss of vermilion show of the upper lip and down sloping of the commissures. In theory, an alar cinch suture combined with a muco-musculo-periosteal V-Y closure (ACVY) should improve not only the nasal width, but would also improve the dynamics of some of the mimic muscles. To test the validity of this hypothesis, a prospective study was set up including 22 patients, using standardized full facial frontal photographs, taken immediately preoperatively and 18 months postoperatively. Sets containing three pictures were made: soft tissue in repose, maximum closed mouth smile and maximum smile. The landmarks, alare, crista philtri and cheilion were analysed. The preliminary results show that ACVY-closure does significantly improve the horizontal movement of cheilion with both maximum closed mouth smile and maximum smile, as well as the vertical movement of crista philtri with maximum closed mouth smile. CONCLUSION The Le Fort I osteotomy with ACVY improves the orofacial dynamics.

Tissue engineering strategies for alveolar cleft reconstruction: a systematic review of the literature

ObjectivesTo date, a great number of tissue engineering strategies have been suggested for alveolar cleft reconstruction; however, autologous bone grafting seems to remain the golden standard.Materials and methodsA systematic review of the literature was conducted in order to evaluate the clinical evidence pertaining to enhancement or replacement of the autologous bone graft in the alveolar cleft by means of tissue-engineered substitutes; 16 articles were selected for analysis.ResultsTissue engineering strategies for alveolar cleft grafting included enhancing the autologous bone graft by means of platelet-rich plasma addition, the use of barrier membranes and fibrin glue, extension of the autologous graft with calcium phosphate scaffolds, and replacement of the graft using bone morphogenetic protein-2, mesenchymal stem cells, or calcium phosphate scaffolds.ConclusionsSelected articles showed a vast heterogeneity in data acquisition and patient selection. Therefore, a meta-analysis could not be performed. Future publications concerning this topic should be methodologically sound and preferably use three-dimensional radiological imaging for pre- and postoperative results.Clinical relevanceBypassing or enhancing autologous bone grafting by means of tissue engineering solutions has become an important topic in alveolar cleft grafting. Replacement of the autologous bone graft will result in absence of donor site morbidity in this predominantly young population.

A Prospective Study on the Effect of Modified Alar Cinch Sutures and V-Y Closure Versus Simple Closing Sutures on Nasolabial Changes After Le Fort I Intrusion and Advancement Osteotomies

PURPOSE The purpose of this study was to determine whether a modified alar cinch suture and V-Y closure (mACVY) have a beneficial effect on labial form after Le Fort I intrusion and advancement osteotomies and whether they result in excessive upward nasal tip rotation. Both are possible effects compared with simple closing sutures (SCS). PATIENTS AND METHODS A prospective study was carried out on 56 patients, 31 with mACVY and 25 with SCS. Lateral cephalograms taken immediately before and 18 months after operation were used, measuring horizontal and vertical changes of the following landmarks: anterior and posterior nasal spine, A-point, incision superior, pronasale, subnasale, labiale superior, and stomion superior, as well as angular changes of sella-nasion-pronasale, and changes in upper vermilion exposure. Statistical analysis was performed on intragroup, paired t test, and intergroup differences, unpaired t test (P < .05). RESULTS The horizontal and vertical changes of labiale superior were significantly larger for mACVY versus SCS, and the angle sella-nasion-pronasale increased in mACVY versus SCS. However, no significant difference was found for vertical changes of the nasal tip. Upper vermilion exposure increased with mACVY versus SCS. CONCLUSION mACVY has a beneficial effect on labial form, and excessive upward rotation of the nasal tip is prevented.

Resection of early oral squamous cell carcinoma with positive or close margins: Relevance of adjuvant treatment in relation to local recurrence: Margins of 3 mm as safe as 5 mm

OBJECTIVES The treatment strategy of early stage oral squamous cell carcinomas (OSCC) resected with close or involved margins is a returning point of discussion. In this study we reviewed the consequences of re-resection (RR), postoperative radiotherapy (PORT) or watchful waiting (WW). PATIENTS AND METHODS Two-hundred patients with a primary resected Stage 1-2 OSCC of the tongue, floor of the mouth and cheek were included and retrospectively analysed. Local recurrence ratio was related to margin status, unfavourable histological parameters (spidery infiltrative, peri-neural and vascular-invasive growth) and postoperative treatment modality. 3-year overall survival (OS) and disease-specific survival (DSS) was calculated in relation to margin status. RESULTS Twenty-two of 200 (11%) patients had pathological positive margins (PM), 126 (63%) close margins (CM), and 52 (26%) free margins (FM). OS and DSS were not significantly different between these groups. Nine of 200 (4.5%) patients developed local recurrent disease. Two (9.1%) had a PM, five (4.0%) a CM and two (3.8%) a FM. Of the nine recurrences, five patients had undergone PORT, one a RR, and three follow-up. Watchful waiting for CM ⩾3 mm with ⩽2 unfavourable histological parameters showed, besides margin status no significant differences with the FM group. CONCLUSION With this treatment strategy, the local recurrence rate was 4.5%. No evidence was found for local adjuvant treatment in case of close margins ⩾3 mm with ⩽2 unfavourable histological parameters. Current data do not support the use of one treatment modality above any other.

Micro-structured calcium phosphate ceramic for donor site repair after harvesting chin bone for grafting alveolar clefts in children

OBJECTIVES The purpose of this study was to evaluate the use of synthetic bone graft material as a filling material at the mandibular symphysis donor site of autologous bone in children. MATERIALS AND METHODS A blinded patient group comprised 20 patients with unilateral (UCLP) or bilateral (BCLP) cleft of lip and palate, all with an indication for alveolar cleft repair. The study took the form of a prospective randomized clinical trial. We used lateral cephalograms for the measurement of the symphyseal donor area defect both peroperatively and at 12 months postoperatively. The data obtained were digitalized and the treatment outcome expressed in numbers. Comparisons with a previous study were made. Histology of biopsies and CT scans were used for visualising bone formation. RESULTS This study demonstrates that the micro-structured, resorbable calcium phosphate ceramic provides good regeneration properties for the repair of a critical size bony defect in children. One year postoperatively, the measurements taken from lateral cephalograms show that there is scarcely any visible residual defect. Histological investigations of the bone biopsies show solid, induced bone formation and almost complete resorption of the micro-structured calcium phosphate. CONCLUSIONS The findings of this study (novel in children) indicate that micro-structured resorbable calcium phosphate is an excellent alternative to autologous bone. The digital findings showed a restored donor site defect significantly indicating the efficacy (i.e., osteoconductivity and resorbability) of this bone substitute. The biopsy histology demonstrated the overall presence of newly formed vital bone and the resorption of the bone substitute. Its use for grafting the alveolar cleft is currently researched and it may become the new standard. CLINICAL RELEVANCE As co-morbidity and prolonged operation time at the donor operation site are inherent to the alveolar cleft repair procedure, the use of the described bone substitute is winning progress.

Watchful waiting of the neck in early stage oral cancer is unfavourable for patients with occult nodal disease

For cT1/2N0 oral squamous cell carcinoma (OSCC), treatment of the neck is a matter of debate. Two treatment strategies were evaluated in this study: selective neck dissection (SND) and watchful waiting (WW). One hundred and twenty-three SND patients and 70 WW patients with cT1/T2N0M0 OSCC of the tongue, floor of mouth, or buccal mucosa were analysed retrospectively. Extracapsular spread (ECS), 3-year overall survival (OS), and disease-specific survival (DSS) were determined. Twenty-nine percent of SND patients and 13% of WW patients had occult nodal disease. WW-N+ patients showed thicker tumours as compared to WW-N0 patients (5mm vs. 2mm, P=0.02). WW-N+ patients showed significantly more ECS as compared to SND-N+ patients (56% vs. 14%, P=0.016) and had a significantly worse 3-year DSS than SND-N+ patients (56% vs. 82%, P=0.02). For T1 OSCCs, a watchful waiting policy is acceptable if tumour thickness proves to be <4mm. Otherwise, an additional treatment of the neck is advised, since WW-N+ patients show more ECS, with a worse DSS than SND-N+ patients.

Microstructured β-Tricalcium phosphate putty versus autologous bone for repair of alveolar clefts in a goat model

For the first time it was demonstrated that an osteoinductive calcium phosphate-based putty is effective in the restoration of complex maxillofacial defects. In these defects, adequate mechanical confinement by multiple bony walls and osteoconduction from multiple surfaces are usually lacking. This study compares the efficacy of a microstructured beta-tricalcium phosphate (β-TCP) putty with autologous bone for the repair of alveolar cleft defects. A total of 10 Dutch milk goats were operated on in a split-mouth study design in which two-wall bony alveolar clefts were created and successively repaired with autologous bone (the gold standard) at one side and β-TCP putty at the other. After 24 weeks of implantation, histomorphometric and micro–computer tomography analyses proved that the β-TCP putty group showed equal bone quality and volume to clefts reconstructed with autologous bone. In addition, surgical handling of the putty is superior to the use of calcium phosphates in a granular form. Therefore, the results of this study open a clear trajectory for the clinical use of β-TCP putty in the reconstruction of the alveolar cleft and other challenging two-wall bony defects.