Decision Considerations and Strategies for Lip Surgery in Patients with Cleft lip/Palate: A Qualitative Study.

Objective: To qualitatively assess surgeons decision making for lip surgery in patients with cleft lip/palate (CL/P). Design: Prospective, non-randomized, clinical trial. Setting: Clinical data institutional laboratory setting. Patients Participants: The study included both patient and surgeon participants recruited from four craniofacial centers. The patient participants were babies with a CL/P requiring primary lip repair surgery (n=16) and adolescents with repaired CL/P who may require secondary lip revision surgery (n=32). The surgeon participants (n=8) were experienced in cleft care. Facial imaging data that included 2D images, 3D images, videos, and objective 3D visual modelling of facial movements were collected from each patient, and compiled as a collage termed the Standardized Assessment for Facial Surgery (SAFS) for systematic viewing by the surgeons. Interventions: The SAFS served as the intervention. Each surgeon viewed the SAFS for six distinct patients (two babies and four adolescents) and provided a list of surgical problems and goals. Then an in-depth-interview (IDI) was conducted with each surgeon to explore their decision-making processes. IDIs were conducted either in person or virtually, recorded, and then transcribed for qualitative statistical analyses using the Grounded Theory Method. Results: Rich narratives/themes emerged that included timing of the surgery; risks/limitations and benefits of surgery; patient/family goals; planning for muscle repair and scarring; multiplicity of surgeries and their impact; and availability of resources. For diagnoses/treatments, surgeons agreed, and level of surgical experience was not a factor. Conclusions: The themes provided important information to populate a checklist of considerations to serve as a guide for clinicians.

Decision Considerations and Strategies for Lip Surgery in Patients with Cleft lip/Palate: A Qualitative Study.

Objective: To qualitatively assess surgeons' decision making for lip surgery in patients with cleft lip/palate (CL/P). Design: Prospective, non-randomized, clinical trial. Setting: Clinical data institutional laboratory setting. Patients Participants: The study included both patient and surgeon participants recruited from four craniofacial centers. The patient participants were babies with a CL/P requiring primary lip repair surgery (n=16) and adolescents with repaired CL/P who may require secondary lip revision surgery (n=32). The surgeon participants (n=8) were experienced in cleft care. Facial imaging data that included 2D images, 3D images, videos, and objective 3D visual modelling of facial movements were collected from each patient, and compiled as a collage termed the 'Standardized Assessment for Facial Surgery (SAFS)' for systematic viewing by the surgeons. Interventions: The SAFS served as the intervention. Each surgeon viewed the SAFS for six distinct patients (two babies and four adolescents) and provided a list of surgical problems and goals. Then an in-depth-interview (IDI) was conducted with each surgeon to explore their decision-making processes. IDIs were conducted either 'in person' or virtually, recorded, and then transcribed for qualitative statistical analyses using the Grounded Theory Method. Results: Rich narratives/themes emerged that included timing of the surgery; risks/limitations and benefits of surgery; patient/family goals; planning for muscle repair and scarring; multiplicity of surgeries and their impact; and availability of resources. In general, there was surgeon agreement for the diagnoses/treatments. Conclusions: The themes provided important information to populate a checklist of considerations to serve as a guide for clinicians.

Specialized Pro-Resolving Mediators Reduce Scarring After Cleft Lip Repair.

Objective: Residual scarring after cleft lip repair surgery remains a challenge for both surgeons and patients and novel therapeutics are critically needed. The objective of this preclinical experimental study was to evaluate the impact of the methyl-ester of pro-resolving lipid mediator lipoxin A4 (LXA4-ME) on scarring in a novel rabbit model of cleft lip repair. Methods: A defect of the lip was surgically created and repaired in eight six-week old New Zealand white rabbits to simulate human cleft lip scars. Rabbits were randomly assigned to topical application of PBS (control) or 1 ug of LXA4-ME (treatment). 42 days post surgery all animals were euthanized. Photographs of the cleft lip area defect and histologic specimens were evaluated. Multiple scar assessment scales were used to compare scarring. Results: Animals treated with LXA4-ME exhibited lower Visual Scar Assessment scores compared to animals treated with PBS. Treatment with LXA4-ME resulted in a significant reduction of inflammatory cell infiltrate and density of collagen fibers. Control animals showed reduced 2D directional variance (orientation) of collagen fibers compared to animals treated with LXA4-ME demonstrating thicker and more parallel collagen fibers, consistent with scar tissue. Conclusions: These data suggest that LXA4-ME limits scarring after cleft lip repair and improves wound healing outcomes in rabbits favoring the resolution of inflammation. Further studies are needed to explore the mechanisms that underlie the positive therapeutic impact of LXA4-ME on scarring to set the stage for future human clinical trials of LXA4-ME for scar prevention or treatment after cleft lip repair.

Evaluation of current additive manufacturing systems for orthodontic 3-dimensional printing.

INTRODUCTION: The objective of this research was to evaluate and compare linear and surface accuracy of dental models fabricated using 3 different vat photopolymerization printing units: digital light synthesis (M2 Printer; Carbon, Redwood City, Calif), digital light processing (Juell 3D Flash OC; Park Dental Research, New York, NY), and stereolithography apparatus (Form 2; Formlabs Inc, Somerville, Mass), and a material jetting printing unit: PolyJet (Objet Eden 260VS; Stratasys, Eden Prairie, Minn). METHODS: Maxillary and mandibular dental arches of 20 patients with the American Board of Orthodontics Discrepancy Index scores ranging between 10 and 30 were scanned using an intraoral scanner. Stereolithographic files of each patient were printed via the 3-dimensional (3D) printers and were digitized again using a 3D desktop scanner to enable comparisons with the original scan data. One-sample t test and linear regression analyses were performed. To further graphically examine the accuracy between the different methods, Bland-Altman plots were computed. The level of significance was set at P <0.05. RESULTS: Bland-Altman analysis showed no fixed bias of one approach vs the other, and random errors were detected in all linear accuracy comparisons. When a 0.25 mm tolerance level was deemed acceptable for any positive or negative surface changes, only the models manufactured from digital light processing and PolyJet units showed more than 97% match with the original scans. CONCLUSION: The surface area of 3D printed models did not yield an utterly identical match to the original scan data and was affected by the type of printer. The clinical relevance of the differences observed on the 3D printed dental model surfaces requires application-specific judgments.

6-Shogaol promotes bone resorption and accelerates orthodontic tooth movement through the JNK-NFATc1 signaling axis.

INTRODUCTION: Corticotomy is widely used in clinical practice to accelerate tooth movement and shorten the duration of orthodontic treatment. It is effective, but an invasive surgery is needed to induce alveolar bone osteopenia that enable rapid tooth movement. In this study, we discovered the potential of 6-shogaol as a more patient-friendly non-invasive alternative to induce transient osteopenia and accelerate tooth movement. MATERIALS AND METHODS: The effects of 6-shogaol on the bone marrow macrophages (BMM) proliferation and osteoclast differentiation, and bone resorption were determined in vitro. Sprague-Dawley rats were distributed into three groups: CON, IPinj or Localinj and euthanized at day 28. Micro-CT, histology, immunohistological, and TUNEL analysis were performed to evaluate the tooth movement acceleration effect of 6-shogaol. RESULTS: In vitro, 6-shogaol promotes osteoclast differentiation and functional demineralization of alveolar bone. RANKL-induced mRNA expression of osteoclastic-specific genes was significantly higher in the presence of 6-shogaol. A dose-dependent increase in the area of TRAP-positive cells was observed with 6-shogaol treatment. F-actin ring formation and increased bone resorption confirmed that osteoclasts treated with 6-shogaol were mature and functional. 6-shogaol stimulated JNK activation and NFATc1 expression during osteoclast differentiation. In vivo, 6-shogaol promotes alveolar bone transient osteopenia and accelerates orthodontic tooth movement. Alveolar bone mass was reduced, more osteoclasts were observed in bone resorption lacunae on the compression side, and the expression of RANKL and sclerostin were higher than the control group. In conclusion, our results suggest that 6-shogoal accelerates tooth movement by inducing osteopenia by a mechanism similar to surgically induced bone injury.

Nasolabial fold dynamics: Implications for facial paralysis and facial reanimation surgery.

OBJECTIVES: In patients with facial paralysis, facial reanimation surgery may be needed to normalize facial soft tissue function/movements. Critical for this normalization is the dynamics of the nasolabial folds (NLFs). The objective of this prospective, observational study was to determine the 3D morphologic dynamics of the NLFs in patients with unilateral facial palsy and normal subjects. SETTINGS AND SAMPLE POPULATION: 3D facial soft tissue movement data collected from adults with unilateral, facial paralysis (Bell's Palsy, n = 36); and (2) an age- and sex-frequency matched control group (n = 68). MATERIALS AND METHODS: Movement data were collected during repeated animations from participants using a video-based motion capture system. Movement in terms of displacement and asymmetry of the NLFs, nasal and circumoral regions were analyzed in the lateral, vertical and depth planes; as well as movement of the commissure and NLFs relative to the lower lip midline. Two-sample t tests were used to test for significant group differences. RESULTS: Patients NLFs had less mean displacement, greater mean asymmetry and uncoordinated movements compared with the controls. For both groups during smiling, the NLF and commissure landmarks had approximately similar magnitudes of displacement (control range = 11-14mm; patient range = 7-10mm). CONCLUSION: NLF dynamics during smiling were as significant as oral commissure excursion. Thus, an immobile NLF is an unnatural feature of facial animations. Surgical treatments that address impaired NFL movements must be considered to create a more natural surgical outcome especially during smiling.

Facial mobility and recovery in patients with unilateral facial paralysis.

OBJECTIVE: (a) To quantify longitudinal 3D changes in facial soft tissue movements in adults with unilateral facial paralysis, and (b) to compare the patients' movements with an age- and sex-frequency matched control group. SETTINGS AND SAMPLE POPULATION: Prospective 3D facial movement data of 36 patients and 68 control participants. Patients' data were collected within 6 weeks of onset of symptoms (baseline) and then at 3 and 12 weeks after baseline. MATERIALS AND METHODS: The 3D facial movement data were collected during different facial animations. Mean group measurements of displacement, velocity and asymmetry were computed. Two sample t tests were used to test for significant group differences, and linear mixed models were fit to test for significant changes over time in the patient group. Also, 3D dynamic modelling and vector plots were computed to isolate the patients' abnormal movements and/or paralysis. RESULTS: The patients' mean baseline movements were significantly less for both the paralysed and contralateral sides of the face with much greater movement asymmetry than the controls. Patients' mean measures improved significantly from baseline to 12 weeks. The measures were closer to, but fell short of, the control values. CONCLUSION: In unilateral facial paralysis, the contralateral facial side was affected by the paralysis and may be tethered or limited in its movement by the paralysed side. The comprehensive measurement set and 3D facial mapping effectively tracked patient recovery and isolated paralysed facial regions. The 3D measures can be used for diagnosis and outcome assessment of different treatments.

Marked Variation Exists Among Surgeons and Hospitals in the Use of Secondary Cleft Lip Surgery.

OBJECTIVE: To identify child-, surgeon-, and hospital-specific factors at the time of primary cleft lip repair that are associated with the use of secondary cleft lip surgery. DESIGN: Retrospective cohort study. SETTING: Forty-nine pediatric hospitals. PARTICIPANTS: Children who underwent cleft lip repair between 1999 and 2015. MAIN OUTCOME MEASURE: Time from primary cleft lip repair to secondary lip surgery. RESULTS: By 5 years after primary lip repair, 24.0% of children had undergone a secondary lip surgery. In multivariable analysis, primary lip repair before 3 months had a 1.22-fold increased hazard of secondary surgery (95% confidence interval [CI]: 1.02-1.46) compared to repair at 7 to 12 months of age, and children with multiple congenital anomalies had a 0.77-fold decreased hazard of secondary surgery (95% CI: 0.68-0.87). After adjusting for cleft type, age at repair, presence of multiple congenital anomalies, and procedure volume, there remained substantial variation in secondary surgery use among surgeons and hospitals (P < .01). For children with unilateral cleft lip repaired at 3 to 6 months of age, the predicted proportion of children undergoing secondary surgery within 5 years of primary repair ranged from 4.9% to 21.8% across surgeons and from 4.5% to 24.7% across hospitals. CONCLUSIONS: There are substantial differences among surgeons and hospitals in the rates of secondary lip surgery. Further work is needed to identify causes for this variation among providers.

Salivary alkaline phosphatase activity and chronological age as indicators for skeletal maturity.

OBJECTIVES: To investigate the relationship between salivary alkaline phosphatase activity (ALP), protein concentration, and chronological age with cervical vertebral maturation stages (CVMS) as noninvasive biomarkers for skeletal maturity assessment. MATERIALS AND METHODS: This cross-sectional study included 79 subjects (48 females, 31 males; 7 to 23 years old) categorized into five CVMS based on lateral cephalographs evaluated by three examiners. ALP activity and protein concentration in unstimulated whole saliva were compared among five CVMS. The association between age and CVMS was assessed and five multinomial logistic regression models were utilized to predict CVMS based on salivary ALP activity, protein concentration, and chronological age. RESULTS: Salivary ALP reached the peak at early pubertal stage and then declined with a significant difference between CVMS I and CVMS II (P < .001) and between CVMS I and CVMS V (P = .004). A significant positive correlation between age and CVMS was found (rs = 0.763, P < .001). The models' overall correct classification rates for predicting CVMS were 32.9% using protein concentration, 35.4% using ALP activity, and 53.2% using both ALP activity and age. CONCLUSIONS: The combination of salivary ALP activity and chronological age may provide the best CVMS prediction.

The role of lip thickness in upper lip response to sagittal change of incisor position.

OBJECTIVES: To investigate the association between upper lip thickness and the amount of upper lip repositioning upon retraction of maxillary incisors. SETTING AND SAMPLE POPULATION: Pre- and post-treatment lateral cephalograms of 101 patients were reviewed. All subjects were treated with fixed orthodontic appliances including extraction of two maxillary premolars. Only subjects without change in lip thickness between pre- and post-treatment cephalograms were included. MATERIAL AND METHODS: Digital software measurements for lip thickness, pre- and post-treatment upper lip position were performed. Appropriate regression models were developed to explore the correlation between maxillary incisor retraction and lip retraction when controlling for lip thickness and other confounding factors. The level of statistical significance was set at 0.05 for all analyses. RESULTS: A significant correlation was found between change in maxillary incisor position following premolars extraction and change in upper lip position (r = 0.95, P < 0.001). The average ratio between maxillary incisor retraction and upper lip repositioning was 1.43:1. Upper lip thickness was not significantly associated with this ratio (r = 0.003, P > 0.05). CONCLUSION: Although there is a highly significant correlation between maxillary incisor retraction and upper lip repositioning, lip thickness is not significantly associated with the amount of repositioning.

Facial Soft-tissue Mobility: Baseline Dynamics of Patients with Unilateral Facial Paralysis.

BACKGROUND: The aims of this observational study were 2-fold: (1) To demonstrate a method and measures to quantify impaired facial soft-tissue movements in patients with facial paralysis; and (2) To quantify the differences in magnitude and velocity of facial soft-tissue movements between patients with facial paralysis and control participants. METHODS: The study sample that addressed both aims consisted of 20 adults with acute, unilateral, flaccid facial paralysis who presented at the onset of their paralysis, and a control group of 20 healthy adults. Dynamic 3D facial movement data were collected from each participant during 11 facial animations. To compare the movements between the patients and control participants, dynamic modeling comparisons of mean facial movements were computed as well as plots of movement vectors for each animation, in addition, measures of maximum displacement, movement velocity, and asymmetry were computed. RESULTS: Dynamic 3D modeling of critical facial landmarks provided precise profiles of zone-specific asymmetries and customized reporting that highlighted areas of importance for individual patients. The dynamic 3D movement data confirmed that the nonparalyzed side of patients' faces had abnormal directional movements. As expected, the controls had significantly higher excursive facial movements during all animations except during gentle eye closure, which was greater for the patients and the controls had significantly greater movement velocity than the patients. The patients had significantly greater asymmetry for all the animations, and the hierarchy of the asymmetry was such that maximum smile > lip purse > grimace > cheek puff. CONCLUSION: Dynamic 3D modeling appeared to be an effective tool to provide precise profiles of zone-specific asymmetries and customized reports for patients with facial paralysis.

Quantifying Soft Tissue Shape and Symmetry: Patients with Cleft Lip/Palate and Facial Paralysis.

BACKGROUND: The objective of this study was to demonstrate simple three-dimensional analyses of facial soft tissue shape and asymmetry. METHODS: There were 2 study samples: one retrospective comprised patients with repaired cleft lip and palate (CL/P) and control subjects; and the other prospective comprised patients with unilateral facial paralysis (FP) and control subjects. The data collected were digitized three-dimensional facial landmarks. Scores for shape and asymmetry of subjects' faces and for different facial regions were generated using Procrustes methods. Pivotal bootstrap methods and analysis of variance were used to test for significant differences in the scores between the patients and controls, and plots of the scores were generated to compare differences among the subjects. RESULTS: (1) Shape scores: The CL/P patients demonstrated significant overall and regional facial differences (P ≤ 0.01). The patients were further from the control mean, especially those with unilateral CL/P. Patients with FP demonstrated significant differences (P ≤ 0.05) for the lower face only. (2) Asymmetry scores: CL/P and FP patients demonstrated significant overall and regional facial differences (CL/P, P ≤ 0.0001; FP, P ≤ 0.01). CL/P and FP patients were more asymmetric and were further from the control mean, and patients with unilateral CL/P were more asymmetric than the bilateral CL/P patients. CONCLUSION: Clinicians can use the analyses to isolate differences and/or changes in the face due to shape or asymmetry, or a combination of both; based on the score plots, the extent of the shape and asymmetry differences can be compared among subjects and the extent of changes due to surgery measured.

Influence of objective three-dimensional measures and movement images on surgeon treatment planning for lip revision surgery.

Objective : To determine whether a systematic evaluation of facial soft tissues of patients with cleft lip and palate, using facial video images and objective three-dimensional measurements of movement, change surgeons' treatment plans for lip revision surgery. Design : Prospective longitudinal study. Setting : The University of North Carolina School of Dentistry. Patients, Participants : A group of patients with repaired cleft lip and palate (n = 21), a noncleft control group (n = 37), and surgeons experienced in cleft care. Interventions : Lip revision. Main Outcome Measures : (1) facial photographic images; (2) facial video images during animations; (3) objective three-dimensional measurements of upper lip movement based on z scores; and (4) objective dynamic and visual three-dimensional measurement of facial soft tissue movement. Results : With the use of the video images plus objective three-dimensional measures, the operating surgeon changed the problem list of the surgical treatment plan for 86% of the patients (95% confidence interval, 0.64 to 0.97) and the surgical goals for 71% of the patients (95% confidence interval, 0.48 to 0.89). The surgeon group varied in the percentage of patients for whom the problem list was modified, ranging from 24% (95% confidence interval, 8% to 47%) to 48% (95% confidence interval, 26% to 70%) of patients, and the percentage for whom the surgical goals were modified, ranging from 14% (94% confidence interval, 3% to 36%) to 48% (95% confidence interval, 26% to 70%) of patients. Conclusions : For all surgeons, the additional assessment components of the systematic valuation resulted in a change in clinical decision making for some patients.

Human umbilical cord stem cell encapsulation in novel macroporous and injectable fibrin for muscle tissue engineering.

There has been little research on the seeding of human umbilical cord mesenchymal stem cells (hUCMSCs) in three-dimensional scaffolds for muscle tissue engineering. The objectives of this study were: (i) to seed hUCMSCs in a fibrin hydrogel containing fast-degradable microbeads (dMBs) to create macropores to enhance cell viability; and (ii) to investigate the encapsulated cell proliferation and myogenic differentiation for muscle tissue engineering. Mass fractions of 0-80% of dMBs were tested, and 35% of dMBs in fibrin was shown to avoid fibrin shrinkage while creating macropores and promoting cell viability. This construct was referred to as "dMB35". Fibrin without dMBs was termed "dMB0". Microbead degradation created macropores in fibrin and improved cell viability. The percentage of live cells in dMB35 reached 91% at 16 days, higher than the 81% in dMB0 (p<0.05). Live cell density in dMB35 was 1.6-fold that of dMB0 (p<0.05). The encapsulated hUCMSCs proliferated, increasing the cell density by 2.6 times in dMB35 from 1 to 16 days. MTT activity for dMB35 was substantially higher than that for dMB0 at 16 days (p<0.05). hUCMSCs in dMB35 had high gene expressions of myotube markers of myosin heavy chain 1 (MYH1) and alpha-actinin 3 (ACTN3). Elongated, multinucleated cells were formed with positive staining of myogenic specific proteins including myogenin, MYH, ACTN and actin alpha 1. Moreover, a significant increase in cell fusion was detected with myogenic induction. In conclusion, hUCMSCs were encapsulated in fibrin with degradable microbeads for the first time, achieving greatly enhanced cell viability and successful myogenic differentiation with formation of multinucleated myotubes. The injectable and macroporous fibrin-dMB-hUCMSC construct may be promising for muscle tissue engineering applications.

Effects of lip revision surgery on long-term orosensory function in patients with cleft lip/palate.

OBJECTIVE : To determine whether secondary lip revision surgery impacts sensitivity of the upper lip. DESIGN : A three-group, parallel, prospective, nonrandomized clinical trial. SETTING : University of North Carolina School of Dentistry. PATIENTS, PARTICIPANTS : Three groups: (1) patients with repaired cleft lip/palate who were scheduled for lip revision (revision; N = 20); (2) patients with repaired cleft lip/palate who did not receive a lip revision (non-revision; N = 13); and (3) non-cleft control subjects (non-cleft; N = 22). Interventions : Lip revision surgery. MAIN OUTCOME MEASURES : Measures of (1) two-point perception threshold (two-point), (2) warmth detection threshold (warm), and (3) cool detection threshold (cool) were obtained from two sites on the upper lip vermilion. The revision participants were tested approximately 1 week before surgery and then approximately 3 and 12 months after surgery. The non-revision and non-cleft participants were tested at similar times. RESULTS : There were no significant differences among the three groups at baseline for two-point, warm, or cool. The main effects of group, age, sex, and time were not statistically significant for the two-point or warm (p > .05). The mean differences between the 3- and 12-month follow-up visits and baseline for two-point and warm were small for all three groups. For cool, group was statistically significant (p = .04), the difference in the non-revision group between follow-up and baseline was 31% to 34% higher than in the non-cleft group (p = .01). CONCLUSIONS : Although at postsurgery revision participants exhibited threshold values comparable to presurgical values, the sensory differences observed among subgroups of participants with cleft lip are complex.

Facial soft tissue dynamics before and after primary lip repair.

Objectives : (1) To collect three-dimensional, dynamic facial images from two groups of infants: one group born with cleft lip and palate slated to have a primary lip repair and a second, age-matched, noncleft control group. (2) To develop analyses to determine differences in facial movement between infants with cleft lip with or without palate (CL±P) and noncleft control infants and to determine changes in facial movement before and after primary lip repair. Design : Longitudinal, prospective case-control study. Setting : Facial Animation Laboratory at the University of North Carolina School of Dentistry. Participants : Two groups of infants: one group with unrepaired CL±P slated to have primary lip repair (n = 15) and a second group of age-matched, noncleft controls (n = 15). Interventions : Movement testing before and 4 months after primary lip repair in infants with CL±P and at similar time points in noncleft infants. Main Outcome Measures : Seven measures of facial movement. Results : The range of facial movements increased by 17% for all infants during the 4-month period. Compared with the noncleft group (1) infants with unilateral CL±P had 50% less nasolabial movement, and this difference did not change due to the lip repair; and (2) infants with unilateral or bilateral CL±P had 58% and 118% greater lateral upper lip movement, respectively, and 3.67 and 3.56 times greater asymmetry of movement, respectively, before lip repair. The procedure almost entirely removed the hypermobility and decreased the asymmetry. Conclusions : Primary surgical lip repair decreased hypermobility and improved asymmetry of upper lip movement.

Fast-degradable microbeads encapsulating human umbilical cord stem cells in alginate for muscle tissue engineering.

Human umbilical cord mesenchymal stem cells (hUCMSCs) are inexhaustible and can be obtained without an invasive surgery. To date, there has been no report on seeding hUCMSCs in three-dimensional scaffolds for muscle tissue engineering. The objectives of this study were to (1) investigate hUCMSC seeding in a scaffold for muscle engineering and (2) develop a novel construct consisting of hUCMSC-encapsulating and fast-degradable microbeads inside a hydrogel matrix. The rationale was that the hydrogel matrix would maintain the defect volume, while the microbeads would degrade to release the cells and concomitantly create macropores in the matrix. hUCMSCs were encapsulated in alginate-fibrin microbeads, which were packed in an Arg-Gly-Asp (RGD)-modified alginate matrix (AM). This construct is referred to as hUCMSC-microbead-AM. The control consisted of the usual cell encapsulation in AM without microbeads (referred to as hUCMSC-AM). In the hUCMSC-AM construct, the hUCMSCs showed as round dots with no spreading at 1-14 days. In contrast, cells in the hUCMSC-microbead-AM construct had a healthy spreading and elongated morphology. The microbeads successfully degraded and released the cells at 8 days. Myogenic expressions for hUCMSC-microbead-AM were more than threefold those of hUCMSC-AM (p<0.05). Immunofluorescence for myogenic markers was much stronger for hUCMSC-microbead-AM than hUCMSC-AM. Muscle creatine kinase of hUCMSC-microbead-AM at 14 days was twofold that of hUCMSC-AM (p<0.05). In conclusion, hUCMSC encapsulation in novel fast-degradable microbeads inside a hydrogel matrix was investigated for muscle engineering. Compared to the usual method of seeding cells in a hydrogel matrix, hUCMSC-microbead-AM construct had greatly improved cell viability and myogenic differentiation, and hence, is promising to enhance muscle regeneration.

Modification of perioral stiffness in patients with repaired cleft lip and palate.

OBJECTIVE: To measure and compare the perioral stiffness among three groups of pediatric subjects: a group of patients with a repaired cleft lip (and palate) who had a secondary lip revision surgery (revision), another group of patients with repaired cleft lip (and palate) who did not have secondary surgery (nonrevision), and a group of noncleft "normal" patients (noncleft). DESIGN: A parallel, three-group, nonrandomized clinical trial. PARTICIPANTS: A total of 16 patients with repaired cleft lip/palate who did not have lip revision, 13 patients with repaired cleft lip/palate who had lip revision surgery and were tested at 18 to 24 months postsurgery, and 27 noncleft patients. ANALYSIS: Nonparticipatory perioral stiffness was sampled using a recently developed face-referenced measurement technology known as OroSTIFF. Perioral stiffness, derived as a quotient from resultant force and interangle lip span, was modeled with multilevel regression techniques. Real-time calculation of the perioral stiffness function demonstrated a significant quadratic relation between imposed interangle stretch and resultant force for each of the three groups. RESULTS: This nonlinear stiffness growth function was significantly elevated in the nonrevision patients compared with the noncleft controls and is likely due to the presence of scar tissue in the upper lip; it was significantly lower among patients with cleft lip/palate who completed lip revision surgery. CONCLUSION: This study demonstrates the efficacy of applying an objective measurement to map differences in perioral tissue biomechanics among patients born with orofacial clefts.

Faces in 4 dimensions: Why do we care, and why the fourth dimension?

The purpose of this article is to describe a dynamic approach for 3-dimensional analyses of facial soft-tissue movements. The method and analysis have numerous applications but, most specifically, are used to assess diagnostic and treatment outcomes of soft-tissue surgery in patients with repaired cleft lip and palate.