Differences in velopharyngeal pressures during speech sound production in patients with unilateral cleft lip and palate (UCLP) and healthy individuals.

Background: During articulation the velopharynx needs to be opened and closed rapidly and a tight closure is needed. Based on the hypothesis that patients with cleft lip and palate (CLP) produce lower pressures in the velopharynx than healthy individuals, this study compared pressure profiles of the velopharyngeal closure during articulation of different sounds between healthy participants and patients with surgically closed unilateral CLP (UCLP) using high resolution manometry (HRM). Materials and methods: Ten healthy adult volunteers (group 1: 20-25.5 years) and ten patients with a non-syndromic surgically reconstructed UCLP (group 2: 19.1-26.9 years) were included in this study. Pressure profiles during the articulation of four sounds (/i:/, /s/, /ʃ/ and /n/) were measured by HRM. Maximum, minimum and average pressures, time intervals as well as detection of a previously described 3-phase-model were compared. Results: Both groups presented with similar pressure curves for each phoneme with regards to the phases described and pressure peaks, but differed in total pressures. An exception was noted for the sound /i:/, where a 3-phase-model could not be seen for most patients with UCLP. Differences in velopharynx pressures of 50% and more were found between the two groups. Maximum and average pressures in the production of the alveolar fricative reached statistical significance. Conclusions: It can be concluded that velopharyngeal pressures of patients with UCLP are not sufficient to eliminate nasal resonance or turbulence during articulation, especially for more complex sounds. These results support a general understanding of hypernasality during speech implying a (relative) velopharyngeal insufficiency.

Dental rehabilitation in irradiated oral cancer patients using patient-specific dental implants - Clinical outcome and oral health-related quality of life.

INTRODUCTION: Dental rehabilitation in oral cancer patients is essential for good oral health-related quality of life (OHRQoL). Patient-specific dental implants are suitable for treating tumor-related bony defects, resulting in satisfactory OHRQoL. However, knowledge concerning the clinical outcome and OHRQoL following tumor irradiation is lacking. MATERIAL AND METHODS: A retrospective analysis was carried out to evaluate clinical outcomes and OHRQoL in eight patients who received patient-specific dental implants and implant-supported dentures after surgical treatment for oral cancer with additional irradiation. OHRQoL assessment was performed using the German long version of the oral health impact profile (OHIP) questionnaire (OHIP-G53). RESULTS: Clinical examination revealed successful dental rehabilitation in all the patients with only minor impairments. Restricted stability and function of implants were not observed. OHIP sum-scores of all the patients indicated acceptable OHRQoL, but this varied between patients treated in the upper or lower jaw. Single-item sum-scores concerning the adverse events "difficulty in chewing," "food catching," "sore jaw," "sore spots," and "unclear speech" were detected to be the worst, and pain-related OHIP dimensions demonstrated the highest scores (followed by functional limitation, physical disability, and psychosocial impact) with a worse OHRQoL following lower jaw treatment. Other dimension sum-scores were overall lower and nearly equally distributed in patients. CONCLUSIONS: Dental rehabilitation of irradiated oral cancer patients using patient-specific dental implants may be suitable, leading to acceptable OHRQoL. However, implant insertion in the upper jaw seems to be more favorable. Further studies on patient-specific dental implants are warranted to validate the current results.

Alendronate reduces periosteal microperfusion in vivo.

Objectives: Bisphosphonates are known to induce a severe adverse effect known as medication-related osteonecrosis of the jaw (MRONJ). Previous studies have proven the impact of bisphosphonates on microperfusion; therefore, this study aimed to investigate alendronate-induced microcirculatory reactions in the calvarial periosteum of rats. Study design: Bone chambers were implanted into 48 Lewis rats. Microhemodynamics, inflammatory parameters, functional capillary density and defect healing were examined after alendronate treatment for two and six weeks using repetitive intravital fluorescence microscopy for two weeks. Results: Microhemodynamics remained unchanged. In alendronate-treated rats, inflammation was slightly increased, functional capillary density was significantly reduced (day 10: controls 100.45 ± 5.38 cm/cm2, two weeks alendronate treatment 44.77 ± 3.55 cm/cm2, six weeks alendronate treatment 27.54 ± 2.23 cm/cm2) and defect healing was decelerated. The changes in functional capillary density and defect healing were dose-dependent. Conclusion: The bisphosphonate alendronate has a significant negative impact on periosteal microperfusion in vivo. This could be a promising target for the treatment of MRONJ.

Socio-demographic aspects and treatment-related factors on oral cancer patients' participation in rehabilitation.

Objectives: After resection of an oral carcinoma, patients are faced with physical, psychological, and socioeconomic challenges. Rehabilitation plays an essential role in patients' reintegration into their social and professional environment. This study evaluated whether socioeconomic aspects affect oral cancer patients' participation in rehabilitation treatment. Materials and methods: A retrospective analysis was conducted with 1,532 patients following surgical treatment of oral cancer during an international multicenter rehabilitation study of the German-Swiss-Austrian Cooperative Working Group on Maxillofacial Tumors using a questionnaire comprising disease-related and psychosocial items postoperatively and at least 6 months after surgery. Results: Only 35.4% of patients participated in rehabilitation. Age (p<0.001), sex (p<0.001), and marital status (p<0.05) significantly influenced participation in rehabilitation. Postoperative impairment (p<0.05) as well as quality of life (p<0.01) were significantly worse in patients who participated in rehabilitation. Nevertheless, this group of patients returned to work significantly more often, although later, than those who did not participate in rehabilitation (p<0.05). Conclusions: The findings show social inequalities and suggest a general undersupply of rehabilitative follow-up treatment in patients with oral cancer. More patients, especially older people and women should be referred to rehabilitation.

Moderately Hypofractionated Radiotherapy Without Chemotherapy in Elderly or Frail Patients With Head and Neck Cancer.

BACKGROUND: Comorbidity and frailty are relevant limitations of normofractionated combined radiochemotherapy for squamous cell head and neck cancer (HNSCC), especially in elderly patients. This retrospective study aimed to evaluate the efficacy and toxicity of moderately hypofractionated radiotherapy (HRT) without chemotherapy in patients ineligible for concurrent radiochemotherapy. PATIENTS AND METHODS: Between 2011 and 2018, 51 elderly/frail patients with HNSCC were treated with either definitive (n=23) or adjuvant (n=28) moderate HRT. A dose of 45 Gy was given to the primary tumour region and cervical nodes with a sequential boost up to 50 in the adjuvant and 55 Gy in the definitive cure setting (2.5 Gy/fraction). Patient outcomes of locoregional control, overall survival, and acute and late toxicity were analysed. RESULTS: After a median follow-up of 6 months for the definitive HRT group and 28.5 months for the adjuvant HRT group, we found a median overall survival of 6 vs. 55 months (log-rank test: p<0.001) and a median locoregional control of 9 months vs. not reached (log-rank test: p=0.008), respectively. The 2-year rates of locoregional control were 28.5% for the definitive HRT group vs. 75.2% for the adjuvant HRT group. No acute or late grade 4-5 toxicity occurred; grade 3 toxicity was rarely documented. CONCLUSION: HRT in elderly/frail patients with HNSCC who are unfit for chemotherapy leads to acceptable local control with moderate toxicity in a short overall treatment time. Especially in the postoperative situation, HRT can be considered an appropriate alternative to normofractionated radio(chemo)therapy. Definitive HRT can be a treatment alternative, especially for multimorbid patients.

Prelamination of the Radial Forearm Free Flap Using Free Full-Thickness Eyelid Skin Grafts: A New Approach for Intraoral Defect Reconstruction.

ABSTRACT: Free flap transfer for reconstruction of intraoral defects is a common procedure in oral and maxillofacial surgery. For tumor-related defects, the radial forearm flap is widely used for soft tissue restoration. However, transfer of free skin grafts to the donor site region is often required for wound closure after free flap harvesting, resulting in esthetic disturbances due to shrinkage of the grafted skin, attendant scarring, or mismatches in skin texture or color. Furthermore, free flap transfer may result in hair follicle transfer into the oral cavity, causing unfavorable intraoral hair growth in adult men in particular. Free flap prelamination can help reduce the potential disadvantages of free flaps, in terms of both flap design and size and donor site morbidity. For surgical treatment of oral cancer in middle-aged and elderly patients, eyelid dermatochalasis may present as a comorbidity leading to esthetic impairments or, in cases involving the upper eyelid, even a reduced field of view. In these cases, bilateral blepharoplasty can reduce the excess eyelid skin. The present study is the first to attempt to use excised skin after bilateral blepharoplasty as full-thickness skin grafts for radial forearm free flap prelamination. This approach combined surgical therapy of eyelid dermatochalasis with free flap prelamination, thereby avoiding the need to harvest free skin grafts from other anatomically healthy regions to close the donor site defect and preventing the accompanying disadvantages. The reconstruction results and clinical outcomes of patients revealed that radial forearm free flap prelamination using bilateral free full-thickness eyelid skin grafts was an easy and feasible method for intraoral defect reconstruction. In particular, this approach could avoid intraoral hair growth and additional skin grafting from other healthy anatomical regions, yielding good esthetic and functional results at the flap's recipient and donor sites.

Quantitative ultrasonographic diagnostics for midface and mandible fractures.

The aim of this study was to examine whether ultrasonography and three-dimensional radiological procedures produce significantly different measurement results with respect to fracture dislocation. This was a retrospective study of patients who were admitted to the department for oral and maxillofacial surgery of the Medical Highschool Hannover with facial skull fracture and underwent high-resolution computed tomography and ultrasonography imaging during a period from 1 January 2019 to 31 August 2019. A 10 mHz transducer was used for fracture imaging, and the largest dislocation of each fracture was measured. A paired t-test for dependent samples was used for statistical evaluation of the measured differences, and the p-value was set at 0.05. A total of 16 patients with 29 fractures were included. The fractures were characterized as follows: zygomatic arch (n = 7), lateroorbital region (n = 4), maxilla/zygomatic bone (n = 15), mandible (n = 2), and frontal sinus (n = 1). Regardless of the fracture location, we found no statistical difference in fracture measurements between the ultrasonography and the computed tomography (p = 0.17 (fractures of the zygomatic arch) to p = 0.85 (all fractures)). The study findings suggest that ultrasonography not only allows basic detection but also a quantification of the dislocation in facial skull fractures. The ultrasonography results are not significantly different from those of the computed tomography. In everyday clinical practice, ultrasonography of facial fractures can be considered an adequate imaging procedure. If used correctly, additional radiation exposure to the patient can be avoided, thus representing a diagnostic alternative to computed tomography.

Retrospective analysis of 15 years of horse-related maxillofacial fracture data at a major German trauma center.

PURPOSE: The purpose of this study was to estimate the effect of the mechanism of trauma (fall versus kick), rider demographics, equestrian experience, protective equipment, and whether or not a horse was shod on the anatomic site of a horse-related maxillofacial fracture, operating time, postoperative complication rate, and length of hospital stay. METHODS: We retrospectively reviewed the medical records of patients treated for horse-related maxillofacial fractures at a single institution in Germany between January 2000 and March 2015. We used linear and logistic regression to test the above-mentioned variables for statistical correlations. RESULTS: During the study period, we treated 138 horse-related facial fractures in 71 patients. The mean patient age was 34.5 years, and 80.3% of the injuries occurred in women. Most of the maxillofacial fractures were the result of a horse kick (71.8%) when unmounted and the majority occurred in more experienced riders (70.4%). There was a significant association of wearing of protective equipment with a shorter hospital stay and lower risk of postoperative complications. CONCLUSION: More education is needed in the equestrian community regarding the use of protective equipment when unmounted. Safety helmets should be redesigned to include a faceguard and be worn at all times.

Postoperative quality of life and therapy-related impairments of oral cancer in relation to time-distance since treatment.

PURPOSE: Oral cancer resection can cause physical and psychological impairments that influence the quality of life (QoL). Depending on the postoperative time-distance, the occurrence and intensity of these impairments may change. We evaluated the sequelae and changes in therapy-related impairments during the postoperative course to detect associations between the time since surgery and the presence of disorders. METHODS: Data from a questionnaire completed by 1359 patients who underwent surgical treatment of oral squamous cell carcinoma and were involved in a multicenter rehabilitation study of the German-Austrian-Swiss Cooperative Group on Tumors of the Maxillofacial Region (DÖSAK) that included 43 oral and maxillofacial clinics in Germany, Austria, and Switzerland were retrospectively analyzed. RESULTS: Physical impairments, including those in appearance, mouth opening ability, ability to smell, gastric disorders, mandible mobility, breathing, and shoulder/arm mobility, were significantly associated with and increased with time-distance since surgery. Esthetic appearance most strongly correlated with the highest perception of worsening. Regarding psychological disorders, worry about tumor recurrence, depression, and worse prospects were significantly associated. Among the postoperative sequelae, fear of tumor recurrence decreased continuously; however, depression and worse prospects increased. The general QoL did not significantly differ overall during the postoperative course. CONCLUSIONS: Therapy-related impairments change during the postoperative course based on the time-distance since surgery. The general QoL may not markedly vary; however, single impairments, to some extent, can increase or decrease. IMPLICATIONS FOR CANCER SURVIVORS: Continuous adaptation of supportive cancer therapy is required during follow-up to sufficiently address individual treatment needs.

Suitability of CD133 as a Marker for Cancer Stem Cells in Melanoma.

OBJECTIVES: CD133 is considered a cancer stem cell (CSC) marker in various malignancies; however, its role as a biomarker of malignant melanoma remains controversial. The present study was conducted to evaluate the suitability of CD133 surface antigen as a CSC marker in melanoma. METHODS: Human melanoma cells were fractionally separated by magnetic cell separation depending on the CD133 phenotype and transplanted into immunodeficient mice to evaluate their tumorigenic capacity. Furthermore, the time until the development of a palpable tumor and the growth rate were measured, and the final tumor volume was assessed after 8 weeks. The immunohistochemical expression of CD133 in the induced neoplasia was then compared using histomorphometry. RESULTS: Notably, neoplasms were induced in all the groups (n = 48), including in the CD133-negative group. Tumors induced by unsorted cells had the largest volume (p = 0.014) but were detected significantly later in this group (p ≤ 0.001). Interestingly, all explanted tumors expressed CD133, with no significant differences among groups. CONCLUSIONS: In contrast to the results obtained in prior studies, the suitability of CD133 as a CSC marker could not be demonstrated. The current encouraging progress in targeted therapy for malignant melanoma highlights the need to identify more effective targets.

CAD/CAM-based referencing aids to reduce preoperative radiation exposure for intraoperative navigation.

BACKGROUND: All intraoperative navigation systems need a referencing procedure prior to utilization, usually requiring an additional computed tomography (CT) or cone beam computed tomograph (CBCT) scan. As new techniques in the field of Computer-aided design / Computer-aided manufacturing (CAD/CAM) have evolved, it seemed favourable to develop a new referencing method not relying on additional CT or CBCT scans. METHODS: A digital maxillary dental scan was used to create a referencing splint by CAD/CAM containing four reference points. By matching scanned dental model and initial trauma-CT, the splints position and thus the reference points were digitally simulated. These splints data were imported into the navigation system in Standard Tessellation Language (STL) format. These data were also 3D printed and the resulting piece was placed on the anatomical models' teeth. The methods accuracy was then assessed in vitro. CONCLUSION: Our method for referencing of intraoperative navigation can be feasible to avoid an additional CT or CBCT prior to navigation.

Fulfillment of patients' information needs during oral cancer treatment and its association with posttherapeutic quality of life.

PURPOSE: Surgical therapy for oral cancer can lead to severe physical and psychological disorders that negatively impact patient quality of life (QoL). This study aimed to evaluate the relationship between fulfillment of patients' information needs during oral cancer treatment and patients' perception of posttherapeutic disorders influencing QoL. METHODS: A retrospective analysis of 1359 patients who were surgically treated for oral cancer using questionnaires administered during the multicenter rehabilitation study by the German-Austrian-Swiss Cooperative Group on Tumors of the Maxillofacial Region (DÖSAK). Patients and medical practitioners completed questionnaires following cancer treatment. RESULTS: Approximately 37% of patients felt inadequately informed about possible physical and psychological consequences of surgery. In contrast, only 16% of patients felt they were given inadequate information about the operative procedure and possible complications, and with regard to tumor diagnosis and cancer disease, only 15% of patients. Significant correlations were found between lacking information and increased perception of posttherapeutic disorders, whereas correlations with tumor-specific and operation-related parameters were markedly lower. The patients with superior QoL after treatment stated more frequently, nearly independent of individual patient characteristics, that the information that they were given prior to therapy was adequate. Information concerning possible physical and psychological consequences of an operation, however, was frequently stated to be inadequate, independent of QoL. CONCLUSION: Patients whose information needs concerning the diagnosis and treatment of oral cancer are adequately fulfilled may benefit in terms of their therapeutic outcome, experiencing less perception of posttherapeutic physical and psychological disorders and a superior QoL.

Influence of Unilateral Cleft Lip Configuration on Long-Term Facial Averageness: A New Three-Dimensional Analysis Approach.

Background: Concepts regarding cleft lip and palate care vary widely globally, as there is no international consensus. Consequently, institutional surveillance of cleft concepts is essential. In addition to subjective expert rankings, three-dimensional (3D) photogrammetry of the face has become the gold standard for evaluation and objective assessment of facial structures. We evaluated cleft configuration preoperatively to determine the influence thereof on the long-term facial appearance/averageness of unilateral cleft lip patients. Methods: Plaster models of the patient's labio-oral region and nose were made preoperatively, digitized, and cleft configuration assessed (cleft width, cleft-columella angle, nasal projection, heminasal width ratio, transverse lip length, labial height). Between 4 and 12 years after surgery, stereophotogrammetry (3D face scans) were captured to determine the patients' individual facial averageness index (FAI) as a deviation from the population mean, using proportion indices (PIs) of facial landmarks and reference data provided by Farkas and FaceBase. Results: Cleft width (r = 0.77) and columella length correlated strongly with long-term facial averageness (r = 0.52). Decreasing FAI was seen with increasing patient age (r = -0.42), indicating increasing facial averageness. Other cleft properties showed weaker correlations. Cleft alveolus did not have any impact on FAI. Conclusions: The presented method allows objective measurement of facial appearance/averageness as well as preoperative cleft properties. It might be superior to subjective assessments of facial attractiveness/appearance. Objective cleft measurements are strong predictors for future facial averageness. Increasing averageness with growth and age suggests late corrective surgery.

Cell seeding accelerates the vascularization of tissue engineering constructs in hypertensive mice.

Rapid blood vessel ingrowth into transplanted constructs represents the key requirement for successful tissue engineering. Seeding three-dimensional scaffolds with suitable cells is an approved technique for this challenge. Since a plethora of patients suffer from widespread diseases that limit the capacity of neoangiogenesis (e.g., hypertension), we investigated the incorporation of cell-seeded poly-L-lactide-co-glycolide scaffolds in hypertensive (BPH/2J, group A) and nonhypertensive (BPN/3J, group B) mice. Collagen-coated scaffolds (A1 and B1) were additionally seeded with osteoblast-like (A2 and B2) and mesenchymal stem cells (A3 and B3). After implantation into dorsal skinfold chambers, inflammation and newly formed microvessels were measured using repetitive intravital fluorescence microscopy for 2 weeks. Apart from a weak inflammatory response in all groups, significantly increased microvascular densities were found in cell-seeded scaffolds (day 14, A2: 192 ± 12 cm/cm2, A3: 194 ± 10 cm/cm2, B2: 249 ± 19 cm/cm2, B3: 264 ± 17 cm/cm2) when compared with controls (A1: 129 ± 10 cm/cm2, B1: 185 ± 8 cm/cm2). In this context, hypertensive mice showed reduced neoangiogenesis in comparison with nonhypertensive animals. Therefore, seeding approved scaffolds with organ-specific or pluripotent cells is a very promising technique for tissue engineering in hypertensive organisms.

Altered bone development with impaired cartilage formation precedes neuromuscular symptoms in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a fatal neurodegenerative disease of newborns and children caused by mutations or deletions of the survival of motoneuron gene 1 resulting in low levels of the SMN protein. While neuromuscular degeneration is the cardinal symptom of the disease, the reduction of the ubiquitously expressed SMN additionally elicits non-motoneuron symptoms. Impaired bone development is a key feature of SMA, but it is yet unknown whether this is an indirect functional consequence of muscle weakness or caused by bone-intrinsic mechanisms. Therefore, we radiologically examined SMA patients in a prospective, non-randomized cohort study characterizing bone size and bone mineral density (BMD) and performed equivalent measurements in pre-symptomatic SMA mice. BMD as well as lumbar vertebral body size were significantly reduced in SMA patients. This growth defect but not BMD reduction was confirmed in SMA mice by µCT before the onset of neuromuscular symptoms indicating that it is at least partially independent of neuromuscular degeneration. Interestingly, the number of chondroblasts in the hypertrophic zone of the growth plate was significantly reduced. This was underlined by RNAseq and expression data from developing SMA mice vertebral bodies, which revealed molecular changes related to cell division and cartilage remodeling. Together, these findings suggest a bone intrinsic defect in SMA. This phenotype may not be rescued by novel drugs that enhance SMN levels in the central nervous system only.

Three-dimensional analysis of the velopharyngeal region in patients with cleft palate and healthy individuals.

PURPOSE: This study aims to attain metric data of the velopharyngeal dimensions of healthy subjects as well as patients with velopharyngeal insufficiency using the example of cleft and lip palate (CLP) in order to determine possible differences in the volumes of both groups. METHODS: Volumes and distances of velopharyngeal areas were analyzed retrospectively using cone beam computed tomography data sets (n = 60). Group 1 included healthy patients receiving dental implants (n = 31). Group 2 was represented by patients with surgically closed cleft lip and palate (n = 29). RESULTS: Biggest differences among mean values of both groups were found for: minimum axial area (p = 0.000), airway area caudal (p = 0.000), distance between posterior nasal spine and posterior pharyngeal wall (PPW) (p = 0.014), mean distance between velum and PPW (p = 0.000), length of PPW (p = 0.000) and length of anterior pharyngeal wall (p = 0.000). CONCLUSION: Differences in the shape and geometry of the velopharyngeal area in subjects with a regular velopharyngeal structure and function and patients with cleft palate do exist. The significant differences found here can be categorized into two groups: one reflects distances between the anterior and posterior pharynx, presenting longer distances for patients with CLP. The second significant difference regards values of length in cranio-caudal direction, which is longer in healthy subjects. With regards to these values, one could conclude, that even though total volumes of both groups did not differ in size, group 1 shows three-dimensional velopharyngeal shapes that are longer and narrower, whereas shapes of patients of group 2 tend to be wider and shorter in general.

Dimensions and position of the Eustachian tube in Humans.

Eustachian tube (ET) dysfunction is one of the causes for chronic otitis media. To develop new therapies such as stents to facilitate middle ear ventilation, a better knowledge on dimensions and positions of the ET in individual patients is necessary. Cone beam CT scans of 143 patients were retrospectively investigated. Parameters such as lengths of the ET and its cartilaginous and bony parts, diameters, angles as well as distance of the ostium from the nasal conchae were determined and evaluated for side, gender and age specific differences. The average length of the cartilaginous and bony tubes was smaller in women than men. The average deviation from the horizontal plane was 1.7° larger on the left side (35.4°) compared to the right side (33.7°). Tools to manipulate the ET or to insert stents into the ET should cover angles from at least 42° to 64°. The distance of the pharyngeal orifices from the conchae nasalis inferior increased with age, becoming most prominent above 70 years of age. This investigation provides necessary information to develop stents for human application and tools for safe positioning of the stents.

Patient-specific implant modification for alloplastic bridging of mandibular segmental defects in head and neck surgery.

Displacement of the remaining mandibular segments may occur after alloplastic bridging of mandibular segmental defects using patient-specific reconstruction plates. Consequently, additional surgical devices are required for correct plate positioning. Patient-specific reconstruction plates with a conventional one beam-like design (cPSRP) have been modified by adding two flanges and giving a Y-shape to the distal ascending implant part to allow for segment positioning without using additional devices. We aimed to evaluate reconstruction results after using these modified patient-specific reconstruction plates (mPSRP). We compared the reconstruction results for mPSRP and cPSRP and evaluated mandibular segment dislocations after reconstruction using digital image analysis of the pre- and postoperative radiological data sets. Analysis showed better reconstruction results with mPSRP than with cPSRP; mean dislocation values concerning shifts and rotations of mandibular segments were lower for mPSRP (x-axis: 2.9 mm vs 1.1 mm, 4.2° vs 3.6°; y-axis: 6.0 mm vs 2.0 mm, 3.5° vs 2.8°; z-axis: 3.9 mm vs 3.3 mm, 4.2° vs 1.2°). Significant differences were found for shifts along the y-axis (p = 0.039) and rotations around the z-axis (p = 0.041). Therefore, implant design modifications with additional positioning elements could help simplify surgical reconstruction procedures and improve reconstruction in head and neck surgery.

Vascularization and biocompatibility of poly(ε-caprolactone) fiber mats for rotator cuff tear repair.

Rotator cuff tear is the most frequent tendon injury in the adult population. Despite current improvements in surgical techniques and the development of grafts, failure rates following tendon reconstruction remain high. New therapies, which aim to restore the topology and functionality of the interface between muscle, tendon and bone, are essentially required. One of the key factors for a successful incorporation of tissue engineered constructs is a rapid ingrowth of cells and tissues, which is dependent on a fast vascularization. The dorsal skinfold chamber model in female BALB/cJZtm mice allows the observation of microhemodynamic parameters in repeated measurements in vivo and therefore the description of the vascularization of different implant materials. In order to promote vascularization of implant material, we compared a porous polymer patch (a commercially available porous polyurethane based scaffold from Biomerix™) with electrospun polycaprolactone (PCL) fiber mats and chitosan-graft-PCL coated electrospun PCL (CS-g-PCL) fiber mats in vivo. Using intravital fluorescence microscopy microcirculatory parameters were analyzed repetitively over 14 days. Vascularization was significantly increased in CS-g-PCL fiber mats at day 14 compared to the porous polymer patch and uncoated PCL fiber mats. Furthermore CS-g-PCL fiber mats showed also a reduced activation of immune cells. Clinically, these are important findings as they indicate that the CS-g-PCL improves the formation of vascularized tissue and the ingrowth of cells into electrospun PCL scaffolds. Especially the combination of enhanced vascularization and the reduction in immune cell activation at the later time points of our study points to an improved clinical outcome after rotator cuff tear repair.

Angiogenic effects of mesenchymal stem cells in combination with different scaffold materials.

Tissue survival in regenerative tissue engineering requires rapid vascularization, which is influenced by scaffold material and seeded cell selection. Poly-l-lactide-co-glycolide (PLGA) and beta-tricalcium phosphate (ß-TCP) are well-established biomaterials with angiogenic effects because of their material properties. Given the importance of the seeded cell type as a co-factor for vascularization, mesenchymal stem cells (MSCs) are known to have high angiogenic potential. We hypothesized that PLGA and ß-TCP scaffolds seeded with MSCs would effectively induce a potent angiogenic response. Therefore, we studied the angiogenic effects after implanting PLGA and ß-TCP scaffolds seeded with isogeneic MSCs in vivo. Fifty-six BALB/c mice were equally divided into seven groups and underwent implantation of the dorsal skinfold chambers. Two MSC groups were seeded on collagen-coated PLGA or ß-TCP scaffolds, whereas groups 3-6 received collagen-coated or uncoated scaffolds without MSCs. No scaffold implantation was performed for group 7, which served as the control. Angiogenesis was assessed in vivo via intravital fluorescence microscopy. Angiogenic responses were noted on all scaffolds, whereupon MSC angiogenic response was significantly enhanced on days 6 and 10. Additionally, a comparison of biomaterials indicated increased angiogenic activity for ß-TCP scaffolds compared with PLGA scaffolds. In conclusion, seeding ß-TCP scaffolds with MSCs can accelerate vitalization and a combination of both significantly improves angiogenesis.