Adipose-derived stem cells mitigate deleterious effects of radiation on bone and enhance radiated fracture healing by replacing damaged cells and stimulating angiogenesis. However, adipose-derived stem cell harvest and delivery techniques must be refined to comply with the US Food and Drug Administration restrictions on implantation of cultured cells into human subjects prior to clinical translation. The purpose of this study is to demonstrate the preservation of efficacy of adipose-derived stem cells to remediate the injurious effects of radiation on fracture healing utilizing a novel harvest and delivery technique that avoids the need for cell culture. Forty-four Lewis rats were divided into 4 groups: fracture control (Fx), radiated fracture control (XFx), radiated fracture treated with cultured adipose-derived stem cells (ASC), and radiated fracture treated with noncultured minimally processed adipose-derived stem cells (MP-ASC). Excluding the Fx group, all rats received a fractionated human-equivalent dose of radiation. All groups underwent mandibular osteotomy with external fixation. Following sacrifice on postoperative day 40, union rate, mineralization, and biomechanical strength were compared between groups at P < 0.05 significance. Compared with Fx controls, the XFx group demonstrated decreased union rate (100% vs 20%), bone volume fraction (P = 0.003), and ultimate load (P < 0.001). Compared with XFx controls, the MP-ASC group tripled the union rate (20% vs 60%) and demonstrated statistically significant increases in both bone volume fraction (P = 0.005) and ultimate load (P = 0.025). Compared with the MP-ASC group, the ASC group showed increased union rate (60% vs 100%) and no significant difference in bone volume fraction (P = 0.936) and ultimate load (P = 0.202). Noncultured minimally processed adipose-derived stem cells demonstrate the capacity to improve irradiated fracture healing without the need for cell proliferation in culture. Further refinement of the cell harvest and delivery techniques demonstrated in this report will enhance the ability of noncultured minimally processed adipose-derived stem cells to improve union rate and bone quality, thereby optimizing clinical translation.

Due to their advantageous characteristics, gold nanoparticles (AuNPs) are being increasingly utilized in a vast array of biomedical applications. However, the efficacy of these procedures are highly dependent upon strong interactions between AuNPs and the surrounding environment. While the field of nanotechnology has grown exponentially, there is still much to be discovered with regards to the complex interactions between NPs and biological systems. One area of particular interest is the generation of a protein corona, which instantaneously forms when NPs encounter a protein-rich environment. Currently, the corona is viewed as an obstacle and has been identified as the cause for loss of application efficiency in physiological systems. To date, however, no study has explored if the protein corona could be designed and advantageously utilized to improve both NP behavior and application efficacy. Therefore, we sought to identify if the formation of a preliminary protein corona could modify both AuNP characteristics and association with the HaCaT cell model. In this study, a corona comprised solely of epidermal growth factor (EGF) was successfully formed around 10-nm AuNPs. These EGF-AuNPs demonstrated augmented particle stability, a modified corona composition, and increased deposition over stock AuNPs, while remaining biocompatible. Analysis of AuNP dosimetry was repeated under dynamic conditions, with lateral flow significantly disrupting deposition and the nano-cellular interface. Taken together, this study demonstrated the plausibility and potential of utilizing the protein corona as a means to influence NP behavior; however, fluid dynamics remains a major challenge to progressing NP dosimetry.

Background: Cell-based treatments have demonstrated the capacity to enhance reconstructive outcomes in recent decades but are hindered in clinical utility by regulatory hurdles surrounding cell culture. This investigation examines the ability of a noncultured stromal vascular fraction derived from lipoaspirate to enhance bone healing during fracture repair to further the development of translatable cell therapies that may improve outcomes in irradiated reconstruction. Methods: Isogenic male Lewis rats were divided into three groups: fracture, irradiated fracture, and irradiated fracture with stromal vascular fraction treatment. Irradiated groups received a fractioned dose of 35 Gy before mandibular osteotomy. Stromal vascular fraction was harvested from the inguinal fat of isogenic donors, centrifuged, and placed intraoperatively into the osteotomy site. All mandibles were evaluated for bony union and vascularity using micro–computed tomography before histologic analysis. Results: Union rates were significantly improved in the irradiated fracture with stromal vascular fraction treatment group (82 percent) compared to the irradiated fracture group (25 percent) and were not statistically different from the fracture group (100 percent). Stromal vascular fraction therapy significantly improved all metrics of bone vascularization compared to the irradiated fracture group and was not statistically different from fracture. Osteocyte proliferation and mature bone formation were significantly reduced in the irradiated fracture group. Bone cellularity and maturity were restored to nonirradiated levels in the irradiated fracture with stromal vascular fraction treatment group despite preoperative irradiation. Conclusions: Vascular and cellular depletion represent principal obstacles in the reconstruction of irradiated bone. This study demonstrates the efficacy of stromal vascular fraction therapy in remediating these damaging effects and provides a promising foundation for future studies aimed at developing noncultured, cell-based therapies for clinical implementation.

Objective: To identify the impact of sociodemographic and health variables on the age at which patients undergo cleft lip repair, cleft palate repair, and primary speech evaluation. Design: A retrospective, noninterventional quality assessment, and quality improvement study was designed. Setting: This institutional study was performed at Michigan Medicine in Ann Arbor, MI. Patients: All patients born between 2011 and 2014 who received surgical cleft repair, excluded those who were adopted (n = 165). Main Outcome Measure: The age at which patients undergo cleft lip repair, cleft palate repair, and primary speech evaluation. Results: Cleft lip repair was performed significantly later for patients identifying as Asian (18 weeks, P = .01), patients with Child Protective Services contact (19 weeks, P = .01), patients with a significant comorbidity (14 weeks, P = .02), and patients who underwent preliminary lip adhesion surgery (19 weeks, P < .01). Cleft palate repair was performed significantly later for patients identifying racially as Asian (19 weeks, P = .03) and other (22 weeks, P = .03). Preliminary speech and language evaluation were performed significantly later for patients identifying as black (55 weeks, P = .03) and patients diagnosed with an isolated cleft lip (71 weeks, P < .01). Conclusions: Timing of cleft lip, cleft palate repair, and primary speech and language evaluation are subject to variation which may be predicted by clinically accessible factors. By identifying race, Child Protective Services contact, and care variables as significant predictors of increased patient age at time of intervention, multidisciplinary cleft care teams can proactively allocate patient support resources.

Background: As craniofacial fellowship positions outnumber the availability of academic craniofacial jobs, it is important to understand the factors associated with securing an academic position after fellowship. The purpose of this study was to evaluate the impact of bibliometric indices and trainee demographics on the ability to obtain a full-time academic plastic surgery position on completion of a craniofacial fellowship. Methods: Craniofacial fellowship graduates between 2009 and 2018 (n = 182) were identified. Initial job placement and demographic data were collected; bibliometric indices at fellowship completion were calculated. Chi-square and Fisher’s exact tests and multivariable logistic regression were used to assess the association of select factors with job placement. Results: Of the 48.9 percent of fellows that secured academic positions, 39.3 percent trained at five fellowship institutions. The majority of those completing residency at top institutions for academic surgery and research entered academic positions at fellowship completion. Geography influenced academic placement, as 72.7 percent of trainees in the Northeast secured academic positions. Only 20.3 percent of fellows completed dedicated postgraduate research time, but among these, 70.3 percent entered academic jobs. The h-index (OR, 1.14; p = 0.01) and total manuscripts (OR, 1.04; p = 0.02) were significantly associated with academic practice while adjusting for other covariates. Conclusions: Although residency training institution, geographic location, and postgraduate research may influence academic placement, the h-index and total manuscripts represent the best predictors of academic careers after craniofacial fellowship. This information is valuable for applicants who aspire to be academic craniofacial surgeons, and for programs and educators who can use these data to identify applicants with a propensity for academics.

Mesenchymal stem cells (MSCs) are capable of differentiating into osteoblasts, chondrocytes, and adipocytes, each of which is important for musculoskeletal tissue regeneration and repair. Reconstruction and healing of bony defects remains a major clinical challenge. Even as surgical practices advance, some severe cases of bone loss do not yield optimal recovery results. New techniques involving implantation of stem cells and tissue-engineered scaffolds are being developed to help improve bone and cartilage repair. The invasiveness and low yield of harvesting MSCs from the bone marrow (BMSCs) has led to the investigation of alternatives, including adipose-derived mesenchymal stem cells (ASCs). A review of the literature yielded several studies concerning the use of BMSCs and ASCs for the treatment of bone defects in both in vitro and in vivo models. Although both ASCs and BMSCs have demonstrated bone regenerative capabilities, BMSCs have outperformed ASCs in vitro. Despite these in vitro study findings, in vivo study results remain variable. Analysis of the literature seems to conclude there is no significant difference between bone regeneration using ASCs or BMSCs in vivo. Improved study design and standardization may enhance the application of these studies to patient care in the clinical setting.

Background-Indications for adjuvant radiation therapy (XRT) in breast cancer have expanded. Although highly effective, XRT damages surrounding tissues and vasculature, often resulting in delayed or compromised breast reconstruction. Thus, effective, yet safe methods of radiation injury prophylaxis would be desirable. Amifostine is a FDA-approved radio-protectant, however, concerns about its potential to also protect cancer remain. The purpose of this study was to evaluate the oncologic safety of Amifostine in vitro and determine its effect on human breast cancer cells in the setting of XRT.Methods-One ER+/PR+/Her2-(MCF-7) and two ER-/PR-/Her2-(MDA-MB-231,MDA-MB-468) breast cancer cell lines were investigated. Female Fibroblasts (FF) were utilized as controls. Cells were treated with WR-1065, the active metabolite of Amifostine, 20 minutes before 0Gy, 10Gy, or 20Gy XRT. Live and dead cells were quantified; percent cell death was calculated.Results-WR-1065 treatment significantly preserved viability and reduced healthy FF death after XRT compared to untreated controls. All three breast cancer cells lines exhibited radiosensitivity with substantial cell death. Cancer cells retained their radio-sensitivity despite WR-1065 pretreatment, achieving the same degree of cell death as untreated controls.Conclusions-This study demonstrated the proficiency of Amifostine to selectively protect healthy cells from XRT, while breast cancer cells continued to remain radiosensitive. These results support the oncologic safety of Amifostine in breast cancer in vitro. Further investigation is now

Background: Although shared decision-making is essential to patient-centered healthcare, its role in pediatric plastic surgery remains unclear. The objective of this study was to define the preferred level of involvement in surgical decision-making among children, caregivers, and surgeons. Methods: The authors surveyed pediatric plastic surgery patients (n = 100) and their caregivers regarding their preferences on child involvement during surgical decision-making. Fleiss’ kappa was used to assess agreement between groups. Bivariate Chi-square tests and multinomial logistic regression were used to assess the relationship between decision-making preferences and select demographic factors. Results: Only 34% of children and their caregivers agreed upon their decision-making preferences (k = 0.04). The majority of children (40%) and caregivers (67%) favored shared decision-making between the patient, caregiver, and surgeon. Only 16% of children preferred physician-driven decisions, while 20% of children desired complete autonomy. Children's preferences were significantly associated with their age; the relative risk of children deferring to caregivers or surgeons over a shared approach was lower for adolescents and teens compared to children under 10 years old (relative risk = 0.20; 95% confidence interval: 0.054–0.751; P = 0.02). Caregiver's preferences did not change based on the child's age, but rather were related to the child's gender. Caregivers were more likely to choose the option that gave the child more autonomy when the child was male. Conclusions: While most caregivers preferred a shared approach to decision-making, children desired greater autonomy, particularly with increasing age. Since there was limited agreement between caregivers and children, surgeons must be cognizant of differing preferences when discussing treatment plans to optimize both patient and parent satisfaction.