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Background In March 2021, the United States Food and Drug Administration (FDA) safety communication cautioned against the use of acellular dermal matrix (ADM) products in breast reconstruction and reiterated that the FDA does not approve ADM use in breast surgery. This study aims to assess the safety of ADM use in breast reconstruction. Methods Women who underwent ADM and non-ADM assisted tissue expander (TE)-based breast reconstruction were identified using the National Surgical Quality Improvement Program database (2012–2019). Trends of ADM use over time, and 30-day outcomes of surgical site infection (SSI), dehiscence, and unplanned reoperation were assessed. Results Of the 49,049 TE-based breast reconstructive cases, 42.4% were ADM assisted and 57.6% non-ADM assisted. From 2012 to 2019, the use of ADM increased from 26.1 to 55.6% (relative risk [RR] =1.10; p Conclusions ADM-assisted breast reconstruction more than doubled from 2012 to 2019. There are statistically higher complication rates of SSI (0.5%) and reoperation (1.4%) with ADM use in TE-based breast reconstruction, suggesting that reconstruction without ADM is safe when comparing immediate postoperative outcomes.

Background While many factors influence decisions related to the timing between mastectomy and flap-based breast reconstruction, there is limited literature comparing postoperative complications between immediate (IBR), delayed immediate (DIBR), and delayed (DBR) reconstruction modalities. Using the National Surgical Quality Improvement Program (NSQIP), we sought to compare postoperative complication rates of each timing modality. Methods The NSQIP 2010–2020 database was queried for patients who underwent free flap breast reconstruction. Cases were categorized to include mastectomy performed concurrently with a free flap reconstruction, removal of a tissue expander with free flap reconstruction, and free flap reconstruction alone which are defined as IBR, DIBR, and DBR, respectively. The frequency of postoperative outcomes including surgical site infection (SSI), wound dehiscence, intraoperative transfusion, deep venous thrombosis (DVT), and return to operating room (OR) was assessed. Overall complication rates, hospital length of stay (LOS), and operative time were analyzed. Multivariable regression analysis controlling for age, race, BMI, diabetes, hypertension, ASA class, and laterality was performed. Results A total of 7,907 cases that underwent IBR, DIBR (n = 976), and DBR reconstruction (n = 6,713) were identified. No statistical difference in occurrence of SSIs, wound dehiscence, or DVT was identified. DIBR (9%) and DBR (11.9%) were associated with less occurrences of reoperation than IBR (13.2%, p Conclusion Awareness of overall complication rates associated with each reconstructive timing modality can be used to help guide physicians when discussing reconstructive options. Our data suggests that DIBR and DBR are associated with less overall complications than IBR. Physicians should continue to consider patients' unique circumstances when deciding upon which timing modality is appropriate.

The Breast Reconstruction Evaluation of Acellular Dermal Matrix as a Sling Trial is a single-center, blinded, prospective, randomized, controlled trial established to compare outcomes using two popular types of acellular dermal matrices, AlloDerm and DermaMatrix, in tissue expander breast reconstruction. This study used the acellular dermal matrix biopsy specimens from the trial to evaluate how adjuvant therapy influences inflammation, neovascularization, and capsule formation of the acellular dermal matrix.Punch biopsy specimens were taken at the time of expander exchange and were analyzed by a blinded pathologist. The inflammatory response was quantified by the number of fibroblasts, giant cells, and lymphocytes. Neovascularization and capsule formation were similarly quantified by the number of new capillaries and capsule presence and thickness, respectively.Histology specimens were collected from 109 patients (170 breasts). In the absence of adjuvant therapy, there was no significant difference between AlloDerm and DermaMatrix in terms of inflammation, neovascularization, or capsule thickness. Both acellular dermal matrices showed a significant decrease in inflammation and neovascularization with adjuvant therapy. When chemotherapy and radiation therapy were used, the decrease in inflammation was greatest for the group reconstructed with DermaMatrix (p0.039).Adjuvant therapy influences the inflammatory response, neovascularization, and capsule formation in both acellular dermal matrices. Adjuvant therapy has a protective effect on the inflammatory response toward both acellular dermal matrices in breast reconstruction. In the setting of chemotherapy and radiation therapy, DermaMatrix produced the greatest reduction in inflammation.Therapeutic, II.

Mastectomy with immediate reconstruction is a high-risk cohort for postoperative nausea and vomiting (PONV). Known risk factors for PONV include female gender, prior PONV history, nonsmoker, age50, and postoperative opioid exposure. The objective of this observational, cohort analysis was to determine whether a standardized preoperative protocol with nonopioid and anti-nausea multimodal medications would reduce the odds of PONV.After IRB approval, retrospective data were collected for patients undergoing mastectomy with or without a nodal resection, and immediate subpectoral tissue expander or implant reconstruction. Patients were grouped based on treatment: those receiving the protocol - oral acetaminophen, pregabalin, celecoxib, and transdermal scopolamine (APCS); those receiving none (NONE), and those receiving partial protocol (OTHER). Logistic regression models were used to compare PONV among treatment groups, adjusting for patient and procedural variables.Among 305 cases, the mean age was 47 years (21-74), with 64% undergoing a bilateral procedure and 85% having had a concomitant nodal procedure. A total of 44.6% received APCS, 30.8% received OTHER, and 24.6% received NONE. The APCS group had the lowest rate of PONV (40%), followed by OTHER (47%), and NONE (59%). Adjusting for known preoperative variables, the odds of PONV were significantly lower in the APCS group versus the NONE group (OR=0.42, 95% CI: 0.20, 0.88 p = 0.016).Premedication with a relatively inexpensive combination of oral non-opioids and an anti-nausea medication was associated with a significant reduction in PONV in a high-risk cohort. Use of a standardized protocol can lead to improved care while optimizing the patient experience.

A percutaneous osseointegrated device becomes deeply ingrown by endosteal bone and traverses the overlying soft tissues of the residual limb, providing a direct link to the bone-anchored artificial limb. Continuous wound healing around these devices can result in the formation of sinus tracts as “down-growing” epithelial cells are unable to recognize and adhere to the “nonbiological” implant surface. Such sinus tracts provide paths for bacterial colonization and deep infection. In order to limit adverse outcomes and provide a robust seal, it was hypothesized that by coating the titanium surface of the percutaneous post with the mineral component of dental enamel, down-growing epidermal cells might recognize the coating as “biological” and adhere to this nonliving surface. To test this hypothesis, sintered partially and fully fluoridated hydroxyapatite (HA) was chosen as coatings. Using an established surgical protocol, fluorapatite (FA), hydroxyfluorapatite (FHA), HA-coated percutaneous posts, and titanium controls were surgically placed under the dorsal skin in 20 CD hairless rats. The animals were sacrificed at four weeks, and implants and surrounding tissues were harvested and subjected to further analyses. Downgrowth and granulation tissue area data showed statistically significant reductions around the FA-coated devices. Moreover, compared to the control group, the FA- and HA-coated groups showed downregulation of mRNA for EGFr, EGF, and FGF-10. Interestingly, the FA-coated group had upregulation of TGF-α. These data suggest that FA could become an ideal coating material for preventing downgrowth, assuming the long-term stability of these coated surfaces can be verified in a clinically relevant animal model.

Background The 5-item modified frailty index (mFI-5) is a validated tool to assess postoperative risks in older surgical candidates. We sought to compare the predictive ability of mFI-5 to its individual components and other established risk factors for complications in flap reconstruction of late-stage pressure ulcer repair. Methods The 2012 to 2018 American College of Surgeons National Surgical Quality Improvement Project (ACS-NSQIP) database was queried for pressure ulcer diagnosis and reconstructive flap repair procedures. Univariate and multivariate regression analysis models were used to assess how mFI-5, the components of the mFI-5 (functional status before surgery, diabetes, history of chronic obstructive pulmonary disease, history of congestive heart failure, and history of hypertension requiring medicine), and other factors commonly used to risk-stratify (age, obesity, ASA classification, and history of smoking) were associated with complications. Results: 35.1% of the total 1254 flap reconstructive procedures for pressure ulcer repair experienced complications. Most cases had at least one of the five mFI-5 factors in both the complication (42.7%) and no complication (45.7%) cohorts. Compared with the factors making up the mFI-5 score and other common variables used to risk-stratify, mFI-5 was significantly associated with complications in the univariate (OR 1.17, CI 1.03 – 1.33; P = 0.02) and multivariate analysis (OR 1.16, CI 1.02 – 1.34; P = 0.043). Conclusions The mFI-5 is a useful predictor of postoperative outcomes in patients undergoing reconstructive flap surgery for pressure ulcer injuries compared to other historically considered risk factors for surgical complications.

The aim of the study is to determine rates of overall complications and failure of prepectoral breast reconstruction between various types of acellular dermal matrices (ADMs).Implant-based breast reconstruction is the most common reconstructive technique after mastectomy in the United States. Traditionally, the reconstruction has been performed in the subpectoral plane; however, there has been an emerging interest in prepectoral reconstruction using ADM. Human (hADM), porcine (pADM), and bovine (bADM) ADMs are available for use, but little is known about the benefits and complication profiles of each for prepectoral breast reconstruction.Studies examining complications after the use of ADM for prepectoral breast reconstruction were identified using MEDLINE, Embase, the Cochrane Library, LILACS, and the Web of Science from January 2010 to August 2021. Titles and abstracts of 1838 studies were screened, followed by full-text screening of 355 articles. Thirty-three studies were found to meet inclusion criteria.From the 33 studies, 6046 prepectoral reconstructions were examined. Implant loss was comparable across the different types of ADM (pADM, 4.0%; hADM, 4.0%; bADM, 3.7%). Bovine ADM had the highest rate of capsular contracture (6.1%), infection (9.0%), skin flap necrosis (8.3%), dehiscence (5.4%), and hematoma (6.1%) when compared with both hADM and pADM. Human ADM had the highest rate of postoperative seroma (5.3%), followed by pADM (4.6%) and bADM (4.5%).Among the prepectoral breast reconstruction studies using hADM, pADM, or bADM included in our analysis, complication profiles were similar. Bovine ADM had the highest proportion of breast complications in the following categories: capsular contracture, infection rate, skin flap necrosis, dehiscence, and hematoma. Implant loss was comparable across the cohorts. Overall, prepectoral breast reconstruction using ADM leads to relatively low complication rates with the highest rates within the bADM cohort.

The Breast Reconstruction Evaluation of Acellular Dermal Matrix (ADM) as a Sling Trial is a blinded, randomized trial comparing the outcomes of tissue expander breast reconstruction using AlloDerm or DermaMatrix. In this final stage of the trial, outcomes three months to two years following definitive reconstruction are reported along with patient satisfaction data.A randomized trial was conducted to compare complication rates between groups reconstructed with AlloDerm and DermaMatrix. Regression models were used to analyze the impact of matrix type, age, chemotherapy, radiation therapy, and reconstructive type on complication rates. Pre- and postmastectomy questionnaires were used to assess patient satisfaction and were also analyzed using regression models.Of the 128 patients (199 breasts) who were randomized in the trial, 108 patients (167 breasts) were available for analysis in stage III. There was no difference in the overall rates of complication between AlloDerm and DermaMatrix groups (6% vs. 13.2%, p=0.3) or the severity of those complications (p=0.7). Obesity was a positive predictor for complications, regardless of reconstruction group (p=0.02). Patient satisfaction was positive overall and did not grossly vary between AlloDerm and DermaMatrix groups.Findings from the BREASTrial conclude that AlloDerm and DermaMatrix exhibit similar histologic and clinical outcomes. Patient satisfaction is also similar between matrices. Obesity is a predictor of complications and acellular dermal matrices should be used with caution in these patients. As the largest head-to-head trial comparing two ADMs, the BREASTrial contributes to fund of knowledge regarding ADM supplementation in breast reconstruction.

Background Despite evidence supporting the safety of breast implants, some women associate their implants with adverse health effects and have called this syndrome “breast implant illness.” We sought to characterize breast implant illness symptoms and to report how implant removal affects their symptoms.Methods An anonymous 20 question survey was administered to the Facebook group: “UTAH Breast Implant Illness” to characterize the symptoms these women attributed to their breast implants. Several questions allowed us to evaluate how implant removal affected women’s symptoms.Results Of the 182 respondents, 97% report that implants negatively affect their health and 95% identify these symptoms with breast implant illness. Ninety-six percent of respondents had implants placed for cosmetic reasons and 51% had silicone implants. The most common symptoms associated with breast implant illness are brain fog (95%), fatigue (92%), joint pain (80%), and hair loss (74%). Sixty percent of respondents learned about breast implant illness from family/friends and/or social media platforms (56%), 40% of respondents had their implants removed, and 97% report relief of their symptoms post-removal (23% complete, 74% partial). Following explantation, there was a significant improvement in all but one reported symptom. An association was found between the number of symptoms reported prior to explantation and the number of symptoms resolving following explantation.Conclusions Breast implant illness is a syndrome characterized by fatigue, decreased focus, hair loss, and joint pain after the placement of breast implants. Nearly all patients report improvement of symptoms after implant removal. Significant efforts should be made to better understand breast implant illness and its etiology.

Background Free tissue transfer is utilized as a reconstructive option for various anatomic defects. While it has long been performed in adults, reconstructive surgeons have used free tissue transfer to a lesser degree in children. As such, there are few analyses of factors associated with complications in free tissue transfer within this population. The aim of this study is to assess factors associated with readmission and reoperation in pediatric free flap patients utilizing the pediatric National Surgical Quality Improvement Program database. Methods Pediatric patients who underwent microvascular reconstruction between 2015 and 2020 were included. Patients were identified by five microvascular reconstruction Current Procedural Terminology codes and were then stratified by flap site (head and neck, extremities, trunk) and defect etiology (congenital, trauma, infection, neoplasm). Multivariate logistic regression was performed to identify factors associated with readmissions and reoperations. Results The study cohort consisted of 258 patients. The average age was 10.0 ± 4.7 years and the majority of patients were male (n = 149, 57.8%), were of white race (n = 164, 63.6%), and had a normal body mass index. Twenty-two patients (8.5%) experienced an unplanned readmission within 30 days of the initial operation, most commonly for wound disruption (31.8% of readmissions). The overall rate of unplanned reoperation within 30 days was 11.6% (n = 30) for all patients, with an average of 8.9 ± 7.5 days to reoperation. On multivariate regression analysis, each hour increase in operative time was associated with an increased odds of reoperation (odds ratio [OR]: 1.27; 95% confidence interval [CI]: 1.12, 1.45) and readmission (OR: 1.16; 95% CI: 1.02, 1.34). Conclusion In pediatric patients undergoing free tissue transfer, higher readmission and reoperation risk was associated with longer operative duration. Overall, free tissue transfer is safe in the pediatric population with relatively low rates of readmission and reoperation.

The introduction of acellular dermal matrix (ADM) to breast reconstruction has allowed surgeons to reexplore the prepectoral implant placement technique in postmastectomy breast reconstruction. Our institution adopted a novel approach using meshed ADM to lessen the financial burden of increased ADM utilization with the prepectoral breast reconstruction. This is a retrospective, single-center review of two-stage prepectoral breast reconstruction using meshed human-derived ADM for anterior prosthesis coverage. Patient demographics, oncologic data, perioperative characteristics, and complications were examined and reported as means with standard deviations. Cost-saving with the meshed technique was evaluated. Forty-eight patients (72 breasts) with a mean age of 48.5 ± 15.0 years (range 26–70 years) were included in the study. The mean follow-up time was 13.2 ± 4.4 months (range 4.1–25.8 months). Nineteen breasts (24.6%) experienced complications, with seromas being the most common complication (12.5%, n = 9). Expander removal and reoperation occurred at a rate of 8.3 and 9.7%, respectively. The average time to drain removal was 18.8 ± 6.6 days (range 8–32 days). Meshed ADM provided an average cost savings of $6,601 for unilateral and $13,202 for bilateral reconstructions. Our study found that human-derived meshed ADM can be safely used in two-staged prepectoral tissue expander-based breast reconstruction and can result in significant cost savings.

In the United States, the top 1% and top 5% of health care spenders account for 23% and 50% of total health care spending, respectively. These high spenders have been coined the term super utilizers (SU). The aim of this study was to identify the characteristics associated with these patients to aid in developing public health interventions aimed at transitioning patients out of the SU category and thus ultimately helping to control health care costs. The authors utilized the Utah All-Payer Claims Database and Utah Population Database from 2013 to 2015 to identify demographics, comorbid conditions, health care utilization, and cost characteristics of persistent super utilizers (PSU) (≥3 hospitalizations per year for 3 years) of health care compared with persistent nonsuper utilizers (PNSU) (3 hospitalizations per year for 3 years). Multivariable logistic regression was utilized to identify the characteristics associated with PSU versus PNSU. Higher outpatient/Emergency Department/noninpatient (eg, visits with imaging and Centers for MedicareMedicaid Services preventive visits) health care utilization and spending, and prevalence of comorbid disease and psychosocial conditions were associated with PSU. In multivariable analysis, factors such as heart disease, chronic kidney disease (CKD), diabetes, alcohol abuse, and depression were statistically significantly associated with higher odds of PSU, with the most noteworthy being CKD (odds ratio [OR] 6.85, 95% confidence interval [95% CI] 5.84-8.02

Background An increasing number of patients undergo contralateral prophylactic mastectomy (CPM) for unilateral breast cancer. However, the benefit of CPM has not been quantified in the setting of contemporary breast cancer therapy. Methods We performed an analysis of 180 068 patients in the Surveillance, Epidemiology, and End Results (SEER) database, diagnosed with unilateral ductal breast carcinoma between 1998 and 2013 and treated with unilateral mastectomy (UM) or CPM. UM was performed in 146 213 patients (81.2%); CPM was performed in 33 855 patients (19.8%). Primary outcome of interest was cumulative incidence of a second primary breast cancer in the ipsilateral or contralateral breast greater than 3 months after initial diagnosis. Cumulative incidence analysis was based on a Cox proportional model to generate curves of second primary breast cancer in any breast, ipsilateral breast only, or contralateral breast only. Results Patients who underwent CPM had a significantly reduced incidence of second primary breast cancer 10 and 15 years after surgery (CPM 0.93% [0.73%, 1.12%] vs UM 4.44% [4.28%, 4.60%]). Patients who underwent CPM had significantly lower adjusted hazard of second primary breast cancer when compared with UM (HR 0.38 vs 1.0, P, We examine second primary breast cancer in the setting of unilateral or bilateral mastectomy using a population‐level database. Our results show that although patients with bilateral mastectomy have reduced odds of second primary breast cancer, this must be interpreted in the context of an overall low rate of second primary breast cancer.

Introduction Flap reconstructions of upper extremity defects are challenging procedures. It is important to understand the surgical outcomes of upper extremity flap reconstruction, as well as associations between preoperative/perioperative variables and complications. Materials and Methods The National Surgical Quality Improvement Program (NSQIP) database was queried for patients from 2005 to 2016 who underwent flap reconstruction of an upper extremity defect. Patient and perioperative variables were collected for identified patients and assessed for associations with rates of any complication and major complications. Results On multivariate analysis, American Society of Anesthesiologists (ASA) classification >2, bleeding disorder, preoperative steroid use, free flap reconstruction, wound classification other than clean, and nonplastic surgeon specialty were independently associated with any complications. Bleeding disorder, ASA classification >2, male gender, wound classification other than clean, and preoperative anemia were independently associated with major complications. Free flap reconstruction was associated with increased length of stay, operative time, any complications, transfusions, and unplanned reoperations. Conclusion There is an association between complications in patients undergoing upper extremity free flap reconstruction and ASA classification >2, preoperative anemia, preoperative steroid use, bleeding disorders, and contaminated wounds. Male patients may require more thorough counseling in activity restriction following reconstruction. Free flaps for upper extremity reconstruction will require increased planning to reduce the chance of complications.

The objective of this work was to develop a model and understand the diffusion of a drug into and throughout a drug delivering nerve conduit from a surrounding reservoir through a hole in the wall separating the lumen of the conduit and the reservoir. A mathematical model based on Fick's law of diffusion was developed using the finite difference method to understand the drug diffusion and the effect of varying device parameters on the concentration of drug delivered from a hole-based drug delivery device. The mathematical model was verified using a physical microfluidic (μFD) model and an in vitro/in vivo release test using prototype devices. The results of the mathematical model evaluation and microfluidic device testing offered positive insight into the reliability and function of the reservoir and hole-based drug delivering nerve conduit. The mathematical model demonstrated how changing device parameters would change the drug concentration inside the device. It was observed that the drug release in the conduit could be tuned by both concentration scaling and changing the hole size or number of holes. Based on the results obtained from the microfluidic device, the error in the mathematical drug release model was shown to be less than 10% when comparing the data obtained from mathematical model and μFD model. The data highlights the flexibility of having a hole-based drug delivery system, since the drug release can be scaled predictably by changing the device parameters or the concentration of the drug in the reservoir. Graphical abstract .

A 7-week-old girl presented with a recurrent primitive myxoid mesenchymal tumor of infancy requiring extensive resection of lower back musculature, L3-S2 vertebral bodies, and left L5 nerve root. Reconstruction consisted of transverse rectus abdominis muscle (TRAM) flow-through to free fibular flap to reconstruct the bony defect and fill the soft-tissue void. One-year postoperative imaging revealed a well-incorporated fibula graft. At the 30-month follow-up, the patient can bear weight on the autograft while sitting upright, allowing for efficient ambulation with a wheelchair.TRAM flow-through to free fibular flap is an efficacious reconstructive method for a multilevel vertebral spinal defect in a pediatric patient.

Smooth symmetric facial muscle function is important for social interactions. When lesions of the facial nerve occur, achieving complete restoration of balanced and spontaneous facial function can be challenging. In this video, the authors demonstrate the surgical details and long-term follow-up of a masseter-to-facial nerve transfer in a 3-year-old girl who had insidious onset of a left facial palsy due to a facial nerve schwannoma. After resection, she underwent distal nerve repair with a masseter-to-zygomatic branch transfer. She demonstrated decreased lagophthalmos and good activation and excursion on the left side with near symmetry to the right side, but lacked left frontalis function. The video can be found here: https://stream.cadmore.media/r10.3171/2022.9.FOCVID22107

Background The rates, severity and consequences of hand and wrist injuries sustained by National Collegiate Athletic Association athletes are not well characterized. This study describes the epidemiology of hand and wrist injuries among collegiate athletes competing in different divisions. Methods The National Collegiate Athletic Association Injury Surveillance Program (NCAA-ISP) was accessed from 2004 to 2015 for the following sports: baseball, basketball, football, ice hockey, lacrosse, soccer, wrestling, field hockey, gymnastics, softball and volleyball. The data were used to identify all hand and wrist injuries, the specific injury diagnosis, mean time loss of activity following injury, and need for surgery following injury. These were then stratified by gender. Descriptive statistics were performed to examine the association between sports, event type and division. Student's t test was used to calculate p-values for independent variables. Chi-Square test was used to calculate odds ratio. P Results 103,098 hand and wrist injuries were reported in in the studied NCAA sports from 2004 to 2015. Male athletes sustained 72,423 injuries (6.01/10,000 athlete exposure) and female athletes sustained 30,675 injuries (4.13/10,000 athlete exposure). Division I athletes sustained significantly more injuries compared to divisions II and III. Overall, 3.78% of hand and wrist injuries required surgical intervention. A significantly higher percentage of division I athletes (both male and female) underwent surgical intervention compared to divisions II and III. The mean time lost due to hand and wrist injury was 7.14 days for all athletes. Division I athletes missed the fewest days due to injury at 6.29 days though this was not significant. Conclusions Hand and wrist injuries are common among collegiate athletes. Division I athletes sustain higher rates of injuries and higher surgical intervention rates, while tending to miss fewer days due to injury. Improved characterization of divisional differences in hand and wrist injuries can assist injury management and prevention.

Although veterans represent a significant proportion (7%) of the USA population, the COVID-19 disease impact within this group has been underreported. To bridge this gap, this study was undertaken.A total of 419,559 veterans, who tested positive for COVID-19 disease in the Veterans Affairs hospital system from March 1st, 2020 to December 31st, 2021 with 60-days follow-up, was included in this retrospective review. Primary outcome measures included age-adjusted incidences and relative incidences of COVID-19 hospitalization, mechanical ventilation, and case-fatality outcomes.Of this veteran cohort with COVID-19 disease, predominately 85.7% were male, 59.1% were White veterans, 27.5% were ages 50-64, and 40.5% were obese. Although Black veterans were at 63% higher relative risk (RR) for hospitalization incidences, they had a similar risk RR for in-hospital deaths compared to the White-veteran referent. Asian, American Indian/Alaska Native races, advanced age ≥65, and the underweight were at high RR for mechanical ventilator and/or in-hospital deaths compared to respective referent groups. Veterans who are ≥85 years old had a nearly 5-fold higher incidence of death compared respective referent group. The monthly outcomes for hospitalization, ventilation, and case-fatality data showed decreasing trends with time.An increased incidence of death was associated with age ≥65 years and underweight veterans compared to the referent group. Age-adjusted data, however, did not show any increased incidence of death in Black veterans compared to White veterans.3 (Case-control studies; retrospective cohort study).

Background Unfractionated heparin infusions are commonly used in microvascular surgery to prevent microvascular thrombosis. Previously, fixed-dose heparin infusions were believed to provide sufficient venous thromboembolism (VTE) prophylaxis; however, we now know that this practice is inadequate for the majority of patients. Anti-factor Xa (aFXa) level is a measure of unfractionated heparin efficacy and safety. This study evaluated the pharmacodynamics of weight-based dose heparin infusions and the impacts of real-time aFXa-guided heparin dose adjustments. Methods This prospective clinical trial enrolled adult microvascular surgery patients who received a weight-based heparin dose following a microsurgical procedure. Steady-state aFXa levels were monitored, and patients with out-of-range levels received dose adjustments. The study outcomes assessed were aFXa levels at a dose of heparin 10 units/kg/hour, time to adequate aFXa level, number of dose adjustments required to reach in-range aFXa levels, and clinically relevant bleeding and VTE at 90 days. Results Twenty-one patients were prospectively recruited, and usable data were available for twenty patients. Four of twenty patients (20%) had adequate prophylaxis at a heparin dose of 10 units/kg/hour. Among patients who received dose adjustments and achieved in-range aFXa levels, the median number of dose adjustments was 2 and the median weight-based dose was 11 units/kg/hour. The percentage of patients with in-range levels was significantly increased (65 vs. 15%, p = 0.0002) as a result of real-time dose adjustments. The rate of VTE at 90 days was 0%, and clinically relevant bleeding rate at 90 days was 15%. Conclusion Weight-based heparin infusions at a rate of 10 units/kg/hour provide a detectable level of anticoagulation for some patients following microsurgical procedures, but most patients require dose adjustment to ensure adequate VTE prophylaxis.

Purpose Cessation of elective surgery during COVID-19 was partly driven by concern for consumption of hospital resources required by critically ill patients. We aim to determine the extent of resource utilization by elective outpatient surgery to assist in ensuring future resource conservation decisions are data driven. Methods The study utilized a retrospective cohort gathered from the American College of Surgeons National Surgical Quality Improvement Program database. Participants were adult patients who underwent elective or non-elective surgery between 2017 and 2018. Outcomes included patient characteristics and post-operative outcomes for elective and non-elective surgeries. Post-operative outcomes were used as a surrogate for the consumption of hospital resources. Results A total of 1,558,938 (79.8%) elective and 393,339 (20.2%) non-elective surgeries were identified. Elective surgery patients were more likely to be outpatient status, have an ASA class

Obesity and diabetes are both associated risk factors for developing breast cancer and poor patient outcomes. Adipose cells are an important endocrine system and are the main producer of adiponectin, with lean patients having higher circulating levels. Patients with diabetes are often treated with thiazolidinediones, glitazones, which also increase adiponectin production. Importantly high circulating levels of adiponectin and treatment with glitazone are associated with increased breast cancer patient survival. This study investigates the potential of using adipose tissue laden with glitazones to act as a drug depot, increase adiponectin levels, and locally release glitazones to inhibit breast cancer cell proliferation. The breast cancer cell lines MCF-7 and MBA-MD-231, and the normal breast epithelial cell line MCF-10A were exposed to media containing a range of concentrations of recombinant adiponectin, pioglitazone, or conditioned media obtained from pioglitazone laden adipose tissue to determine the impact of the different treatments on cell proliferation. The MCF-7 cells demonstrated the greatest reduction in proliferation upon exposure to adiponectin and pioglitazone with lower reductions observed in the MDA-MD-231 and MCF-10a cell lines. All three cell lines exhibited reductions in proliferation in the presence of pioglitazone loaded adipose tissue. Additionally, adiponectin and pioglitazone levels were higher in the media from glitazone loaded adipose tissue. Drug loaded adipose tissue could potentially be used to deliver adiponectin and glitazone to breast cancer cells and inhibit proliferation. Future research will examine the potential efficacy of this treatment approach in vivo.

Background As posterior component separation techniques continue to gain popularity there is uncertainty regarding the degree of fascial advancement afforded by the various techniques. Our study seeks to compare the degree anterior rectus sheath translation seen in full transversus abdominus release compared to simple release of the posterior lamella of the rectus sheath. Methods Ten hemi-abdomens in five fresh cadavers were dissected. One hemi-abdomen underwent external oblique release. The contralateral hemi-abdomen underwent retrorectus dissection and initial release of the internal lamella of the internal oblique, followed by full transversus abdominus release. A 4 kg weight was suspended from the fascia and excursion was measured after 1) external oblique separation, 2) posterior lamella of the internal oblique separation, and 3) transversus abdominis separation. Results Average unilateral hemifascial translation after release of the external oblique provided an average unilateral hemi-fascial translation of 3.38 cm (+/- 0.69). Release of the posterior lamella of the internal oblique provided 3.98 cm (+/- 0.94). After transversus release the average translation increased to 4.31 cm (+/- 0.89). Conclusions In this cadaveric study, the majority (92%) of fascial advancement afforded by posterior component separation was achieved by an intermediate step in the transversus abdominus release operation: division of the posterior lamella of the internal oblique.

BACKGROUND Lower extremity free flaps are a common way to treat both traumatic and oncologic lower extremity wounds. These patients often suffer postoperative complications. We sought to use the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database to identify variables associated with postoperative complications. METHODS Patients who had free flap procedure and a primary diagnosis code for lower extremity pathology were identified in the NSQIP database from 2006 to 2017. NSQIP includes data on preoperative, intraoperative, and postoperative variables, including information up to 30 postoperative days. Current procedural terminology (CPT) codes for free flaps and international classification of diseases (ICD) 9 and 10 codes for lower extremity pathology were used for our cohort. We examined overall and major complication rates. Major complications were defined as reoperation, readmission, organ space infection, or death. Univariate and multivariate analyses were used to identify associations with complications. RESULTS Four hundred and eighty-three patients underwent lower extremity free flaps. Overall complication rate was 31.6% and major complication rate was 14.9%. Prolonged operative time (OR = 2.81, CI:1.76-4.48, p

The wound healing process in the soft tissues adjacent to percutaneous implants induces “epithelial downgrowth”, and subsequently, a sinus tract around the device. This provides an optimal environment for bacterial colonization and proliferation. In an attempt to arrest downgrowth and achieve epithelial attachment to a device surface, we have sought to mimic the most common and successful percutaneous organ, the tooth. Since teeth are composed of partially and fully fluoridated forms of hydroxyapatite (HA), it was hypothesized that the surface properties of fluoridated apatites, fluorohydroxyapatite (FHA) and fluorapatite (FA), would improve epithelial cellular adhesion and differentiation when compared to HA and titanium (Ti) surfaces. In this study, the apatites (HA, FHA, and FA) were synthesized and characterized. Following a high-temperature sintering treatment of these apatites, keratinocyte and fibroblast adhesion and differentiation properties were analyzed in vitro, revealing a statistically significant increase in keratinocyte adhesion and terminal differentiation on FA surfaces sintered at 1050–1150 °C as compared to Ti or HA. Moreover, fibroblasts displayed enhanced adhesion on FHA surfaces. This data suggests that percutaneous devices coated with, or fabricated from, fluoridated apatites may induce improved epithelial cellular adhesion and differentiation, potentially limiting deeply penetrating epithelial downgrowth and resultant bacterial ingress.

Background Bilateral mastectomy rates are increasing in the United States. The abdomen is the most common harvest site for autologous reconstruction. Nationwide data were examined to determine differences in hospital charges, length of stay (LOS), and early postoperative complications following immediate bilateral pedicled transverse rectus abdominis myocutaneous (pTRAM), free TRAM (fTRAM), deep inferior epigastric perforator (DIEP), and superficial inferior epigastric artery (SIEA) perforator flaps and were compared with unilateral reconstruction. Methods Patients who underwent immediate bilateral breast reconstruction using a single method of abdominally based reconstruction were identified using the 2009 to 2014 Nationwide Inpatient Sample Database. Outcomes included total hospital charges, LOS, and immediate postoperative complications. Results We identified 13,348 cases of bilateral mastectomy with a single type of immediate bilateral autologous flap reconstruction. The majority were bilateral DIEP flaps. Mean total cost for bilateral pTRAM, fTRAM, DIEP, and SIEA flaps was US $21,886.80, US $28,839.40, US $30,051.30, and US $33,784.90, respectively (p 0.1). Conclusion Immediate complication rates were higher in bilateral free flaps compared with bilateral pedicled flaps. pTRAM and fTRAM flap reconstructions are still performed frequently with acceptable immediate results without considering long-term morbidity, aesthetics, and abdominal muscle function. Bilateral SIEA free flaps were associated with significantly higher total cost, LOS, and complication rates compared with other groups. Complications were similar between unilateral and bilateral reconstruction procedures. While cost is significantly greater for bilateral procedures compared with unilateral pTRAM, fTRAM, and DIEP flaps, it is not doubled.

Background Traditionally, a 30-day postoperative period is used to assess outcomes in surgery. However, it is not clear if this is sufficient. Our study assessed readmissions and their risk factors following the surgical repair of pressure ulcers in a 90-day postoperative period. Methods Patients with a pressure ulcer to the lower back, hip, and/or buttocks who underwent a pedicled or flap based wound operation were identified in the National Readmissions Database. We then analyzed risk factors for overall 0–90-day readmissions, early readmissions (0–30 days), and late-readmissions (31–90 days). Results 3329 patients were identified, of which 154 (4.66%) had surgical wound-related readmissions. A majority of these occurred after 30 days (53.89%). 90% of patients with a surgical-wound related readmission were readmitted within 63 days of index procedure. Conclusions The traditional 30-day outcome period is not enough to properly assess outcomes in pressure ulcer surgery such as readmission. We demonstrate that a period of at least 10 weeks and perhaps the entire global 90-day postoperative period would be more appropriate to evaluate readmissions after ulcer repair.

Summary Background Breast reduction is one of the most common procedures performed by plastic surgeons. Despite good outcomes and high patient satisfaction, there are little national data on the predictors that lead to complications in this patient population. We accessed a national outcomes database to examine these factors. Methods This is a retrospective study examining the National Surgical Quality Improvement Program database from 2006 to 2015. Patients who underwent primary breast reduction were identified. Patients who underwent any cancer-related procedures were excluded. We identified patient-related and procedure-related factors for analysis. Univariate and multivariate logistic regression analyses were used to identify independent predictors of complications. Results In total, 16,812 individual cases were identified. The overall complication rate for the cohort was 6.2%, and the major complication rate was 3.0%. Diabetes, bleeding disorder, hypertension, obesity, smoking, steroid use, and prolonged operative time were associated with increased risk of complications (p Conclusions Common surgical risk factors are associated with complications in breast reduction surgery. Although liposuction is not an independent risk factor, concurrent body contouring is associated with increased complications. Surgeons should be aware of these associations when discussing breast reduction with patients.

Background Despite high expenditure, there is little national data on rates of complications following pressure ulcer repair. Complications, mortality and their predictors following surgical repair of pressure ulcers were evaluated. Methods Patients undergoing pressure ulcer repair were identified in the NSQIP database from 2005 to 2015. Regression models were used to identify risk factors for complications. Results 1248 cases were identified with a complication rate of 35.0%. Obesity was associated with increased risk of complications, whereas flap closure was associated with fewer complications. Thirty-day mortality was 3.3%. Elderly age and diabetes were associated with increased mortality. Conclusions Elderly age, diabetes and dependency are associated with increased mortality following pressure ulcer surgery. Flap repair is associated with decreased complications. Pressure ulcer reconstruction requires careful patient selection and surgical technique to mitigate risks and mortality.

The accepted "one-size-fits-all" dose strategy for prophylactic enoxaparin may not optimize the medication's risks and benefits after surgical procedures. The authors hypothesized that weight-based administration might improve the pharmacokinetics of prophylactic enoxaparin when compared to fixed-dose administration.The FIxed or Variable Enoxaparin (FIVE) trial was a randomized, double-blind trial that compared the pharmacokinetic and clinical outcomes of patients assigned randomly to postoperative venous thromboembolism prophylaxis using enoxaparin 40 mg twice daily or enoxaparin 0.5 mg/kg twice daily. Patients were randomized after surgery and received the first enoxaparin dose at 8 hours after surgery. Primary hypotheses were (1) weight-based administration is noninferior to a fixed dose for avoiding underanticoagulation (anti-factor Xa0.2 IU/ml) and (2) weight-based administration is superior to fixed-dose administration for avoiding overanticoagulation (anti-factor Xa0.4 IU/ml). Secondary endpoints were 90-day venous thromboembolism and bleeding.In total, 295 patients were randomized, with 151 assigned to fixed-dose and 144 to weight-based administration of enoxaparin. For avoidance of under anticoagulation, weight-based administration had a greater effectiveness (79.9 percent versus 76.6 percent); the 3.3 percent (95 percent CI, -7.5 to 12.5 percent) greater effectiveness achieved statistically significant noninferiority relative to the a priori specified -12 percent noninferiority margin (p = 0.004). For avoidance of overanticoagulation, weight-based enoxaparin administration was superior to fixed-dose administration (90.6 percent versus 82.2 percent); the 8.4 percent (95 percent CI, 0.1 to 16.6 percent) greater effectiveness showed significant safety superiority (p = 0.046). Ninety-day venous thromboembolism and major bleeding were not different between fixed-dose and weight-based cohorts (0.66 percent versus 0.69 percent, p = 0.98; 3.3 percent versus 4.2 percent, p = 0.72, respectively).Weight-based administration showed superior pharmacokinetics for avoidance of underanticoagulation and overanticoagulation in postoperative patients receiving prophylactic enoxaparin.Therapeutic, I.

Hydrogel crosslinking by external stimuli is a versatile strategy to control and modulate hydrogel properties. Besides photonic energy, thermal energy is one of the most accessible external stimuli and widely applicable for many biomedical applications. However, conventional thermal crosslinking systems require a relatively high temperature (over 100 °C) to initiate covalent bond formation. To our knowledge, there has not been a thermally tunable hydrogel crosslinking system suitable for biological applications. This work demonstrates a unique approach to utilize temperature sensitive liposomes to control and modulate hydrogel crosslinking over mild temperature range (below 50 °C). Temperature sensitive liposomes were used to control the release of chemical crosslinkers by moderate temperature changes. The thermally controlled crosslinker release resulted in tunable mechanical and transport properties of the hydrogel. No significant inflammable response observed in the histology results ensured the biocompatibility of the liposome-mediated crosslinkable hydrogel. This work opens new opportunities to implement thermal energy system for control and modulate hydrogel properties.

Purpose Veterans represent a significant proportion of the U.S. population (7%), and the impact of the coronavirus disease 2019 (COVID-19) in this group of vulnerable patients has been largely overlooked. This analysis reports COVID-19 patient demographics, infection, mortality, and case-fatality rates in the veteran population. Methods This is a cross-sectional analysis using the Veterans Affairs informatics and computing infrastructure tool to assess the veterans' COVID-19 infections at the Veterans Affairs facilities from March 4th to June 23rd, 2020. Results Of the 10,621,580 veterans in this analysis, 59.7% were ≥65 yo, 92.5% were men, 68.7% were white, and 14.2% were black. Veterans ≥65 yo comprised 52.1% of cases and 89.9% of deaths. The relative mortality and case-fatality rates of black veterans, when compared with white veterans, were 2.83 (CI 2.56–3.14; P

Introduction: Distal radius fractures are a common injury of the hand and wrist that often require intensive rehabilitation. We sought to identify risk factors associated with discharge to a post-acute care facility following distal radius fracture repair. Methods: The 2011 to 2016 National Surgical Quality Improvement Program® (NSQIP) database was queried for all Current Procedural Terminology (CPT) codes that corresponded with open distal radius fracture repair. Patients with concomitant traumatic injuries were excluded. Patient demographics, comorbidities, perioperative factors, laboratory data, and surgical details were collected. Our primary outcome was to determine postoperative discharge destination: home versus a post-acute care facility, and to identify factors that predict discharge to post-acute care facility. Secondary outcomes included unplanned readmission, reoperation, and complications. Results: Between 2011 and 2016, a total of 12,001 patients underwent open distal radius fracture repair and had complete information for their discharge. Of these analyzed patients, 3.24% (n = 389) were discharged to rehabilitation facilities. The following factors were identified on multivariate analysis to have an association with discharge to a post-acute care facility: 65 years or older, White race, underweight, using steroids preoperatively, American Society of Anesthesiologists (ASA) classification > 2, admitted from a nursing home or already hospitalized, anemic, undergoing bilateral surgery, wound classification other than clean, and complications prior to discharge. Conclusion: Factors identified by our study to have associations with discharge to post-acute care facilities following distal radius fracture repair can help in appropriate patient counseling and triage from the hospital to home versus a post-acute care facility.

There is limited evidence for appropriate post-operative opioid prescribing in breast reconstruction patients. We sought to describe postoperative outpatient prescription opioid use patterns (quantity and duration) following discharge after immediate breast reconstruction with tissue expanders (TE) and to identify demographic and/or clinical risk factors associated with postoperative outpatient opioid use.Patients 18 years and older undergoing immediate TE-based breast reconstruction were given a 28-day postoperative pain medication log book. Descriptive statistics were performed to describe the quantity and duration of opioid use. Preoperative, intraoperative, and postoperative characteristics were examined and tested for their associations with postoperative opioid use.A total of 45 logbooks were completed. On average, patients used opioids for 7.42 days (SD = 6.45) after discharge home and used 15.9 (SD = 18.71) oxycodone 5 mg tablet equivalents (119.3 morphine milligram equivalents, SD = 140.31). The total number of oxycodone 5 mg equivalents consumed prior to discharge was associated with the amount of post-discharge opioid consumption (IRR=1.08, p0.01). Each additional year of age was associated with a reduction in the days-to-opioid cessation by a factor of 0.97 (p=0.01). Each additional oxycodone 5mg equivalent consumed prior to hospital discharge was associated with an increase in the days-to-cessation after discharge by a factor of 1.04 (p=0.026).These patient-reported data will provide a benchmark which plastic surgeons can use to minimize narcotic use in patients and will help prevent issues of dependence, misuse, and diversion, while being mindful of adequate pain control. For patients discharging home after a one-night stay for immediate TE breast reconstruction, we recommend a prescription for 10 oxycodone 5 mg tablets, or 15 tablets if they are less than age 49 or have had high inpatient opioid use. Patients should also be counseled that the expected duration of outpatient opioid use is 7-11 days, and that 20 % of patients did not use any opioids following hospital discharge, making nonnarcotic pain regimens a real possibility.

Supplemental Digital Content is available in the text., Background: Both the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) and the American Society of Plastic Surgeons Tracking Operations and Outcomes for Plastic Surgeons (TOPS) databases track 30-day outcomes. Methods: Using the 2008–2016 TOPS and NSQIP databases, we compared patient characteristics and postoperative outcomes for 5 common plastic surgery procedures. A weighted TOPS population was used to mirror the NSQIP population in clinical and demographic characteristics to compare postoperative outcomes. Results: We identified 154,181 cases. Compared with NSQIP patients, TOPS patients were more likely to be younger (47.9 versus 50.0 years), have American Society of Anesthesiologists class I-II (92.1% versus 74.6%), be outpatient (66.0% versus 49.3%), and be smokers (18.7% versus 11.7%). TOPS had extensive missing data: body mass index (40.6%), American Society of Anesthesiologists class (34.9%), diabetes (39.3%), and smoking status (37.2%). NSQIP was missing

Background Traditionally, surgical quality outcomes are assessed using a 30-day postoperative window. For breast cancer patients undergoing free tissue transfer for breast reconstruction, we sought to describe the distribution of and specific risk factors for early and late readmissions within a 0- to 90-day postoperative period. Patients and Methods The Nationwide Readmissions Database was used to conduct a retrospective cohort study. Breast cancer patients undergoing free tissue transfer for breast reconstruction were identified using International Classification of Diseases -9 diagnosis and procedure codes. Ninety-day readmissions related to infection or wound complications were identified. Univariable and multivariable logistic regression models were used to identify patient risk factors for readmissions that occurred early (0–30 days) and late (31–90 days) after their index procedure. Results In the weighted sample, we identified approximately 7,305 free flap breast reconstructions and a surgical wound-related readmission rate of 4.3% (n = 312): 65.4% of the readmissions occurred early while 34.6% occurred late after surgery. The mean days to readmission was 26, and 75% of all readmissions occurred within the first 36 days after surgery. Variables independently associated with readmissions during the 0- to 90-day postoperative period included: history of chronic obstructive pulmonary disease (p = 0.036), hypertension (p = 0.03), obesity (p ≤ 0.001), and history of smoking (p = 0.004). The variables independently associated with the early readmission period were the same as those identified for the 0- to 90-day postoperative period. The variables independently associated with late readmissions were different: history of depression (p = 0.001) and history of smoking (p = 0.001). Conclusion The conventional 30-day hospital readmission rate classically used as a quality metric is overlooking a significant portion of admissions after free flap-based breast reconstruction. Different variables were found to be associated with readmission in the early versus late cohorts. Interventions targeting these variables could decrease readmissions and their associated costs.

The purpose of this research was to evaluate a novel long-acting bupivacaine delivery system for control of postoperative pain. Bupivacaine-loaded lipid emulsion (BLE) droplets were created by high-speed homogenization. The BLE droplets were then entrapped into a crosslinked-hyaluronic acid hydrogel system to create an injectable composite gel formulation (HA-BLE). Dynamic light scattering, rheological, and drug release techniques were used to characterize the formulations. A rat sciatic nerve block with a thermal nociceptive assay was used to evaluate the anesthetic effect in comparison to controls, bupivacaine HCl and liposomal bupivacaine. The BLE droplets had a zeta potential, droplet size, and polydispersity index of −40.8 ± 0.66 mV, 299 ± 1.77 nm, and 0.409 ± 0.037, respectively. The HA-BLE formulation could be injected through 25 g needles and had an elastic modulus of 372 ± 23.7 Pa. Approximately 80% and 100% of bupivacaine was released from the BLE and HA-BLE formulations by 20 and 68 h, respectively. The HA-BLE formulation had a 5-times greater anesthetic area under the curve and an anesthetic duration that was twice as long as controls. Results indicate that incorporating the BLEs into the hydrogel significantly increased anesthetic effect by protecting the BLE droplets from the in vivo environment.

Purpose Neurotrophic keratopathy is a degenerative disease that may be improved by nerve growth factor (NGF). Our aim was to investigate the use of pergolide, a dopamine (D1 and D2) receptor agonist known to increase the synthesis and release of NGF for regeneration of damaged corneal nerve fibers. Methods Pergolide function was evaluated by measuring axon length and NGF levels by enzyme-linked immunosorbent assay in cultured chicken dorsal root ganglion (DRG) cells with serial doses of pergolide (10, 25, 50, 150, and 300 µg/ml) and with different concentrations of a D1 antagonist. Pergolide function was further evaluated by cornea nerve fiber density and wound healing in a cornea scratch mouse model. Results Pergolide increased DRG axon length significantly at a dose between 50 and 300 µg/ml. Different concentrations of D1 antagonist (12, 24, 48, and 96 µg/ml) inhibited DRG axon length growth with pergolide (300 µg/ml). Pergolide (50 µg/ml) upregulated NGF expression in DRG cells at both 24 hours and 48 hours. Pergolide improved cornea nerve fiber density at both 1 week and 2 weeks. Pergolide also improved cornea wound healing. Conclusions We demonstrated that pergolide can act to promote an increase in NGF which promotes corneal nerve regeneration and would therefore improve corneal sensation and visual acuity in eyes with peripheral neurotrophic keratopathy.

Purpose Hydroxyapatite (HA) scaffolds are common replacement materials used in the clinical management of critical-sized bone defects. This study was undertaken to examine the potential benefits of fluoridated derivatives of hydroxyapatite, fluorapatite (FA), and fluorohydroxyapatite (FHA) as bone scaffolds in conjunction with adipose-derived stem cells (ADSCs). If FHA and FA surfaces could drive the differentiation of stem cells to an osteogenic phenotype, the combination of these ceramic scaffolds with ADSCs could produce materials with mechanical strength and remodeling potential comparable to autologous bone. This study was designed to investigate the ability of the apatite surfaces HA, FA, and FHA produced at different sintering temperatures to drive ADSCs toward osteogenic lineages. Methods: HA, FHA, and FA surfaces sintered at 1150 °C and 1250 °C were seeded with ADSCs and evaluated for cell growth and gene and protein expression of osteogenic markers at 2 and 10 days post-seeding. Results: In vitro, ADSC cells were viable on all surfaces; however, differentiation of these cells into osteoblastic lineage only observed in apatite surfaces. ADSCs seeded on FA and FHA expressed genes and proteins related to osteogenic differentiation markers to a greater extent by Day 2 when compared to HA and cell culture controls. By day 10, HA, FA, and FHA all expressed more bone differentiation markers compared to cell culture controls. Conclusion: FA and FHA apatite scaffolds may promote the differentiation of ADSCs at an earlier time point than HA surfaces. Combining apatite scaffolds with ADSCs has the potential to improve bone regeneration following bone injury.

Autologous nerve grafts are the current "gold standard" for repairing large nerve gaps. However, they cause morbidity at the donor nerve site and only a limited amount of nerve can be harvested. Nerve conduits are a promising alternative to autografts and can act as guidance cues for the regenerating axons, without the need to harvest donor nerve. Separately, it has been shown that localized delivery of GDNF can enhance axon growth and motor recovery. FK506, an FDA approved small molecule, has also been shown to enhance peripheral nerve regeneration. This paper describes the design of a novel hole-based drug delivery apparatus integrated with a polytetrafluoroethylene (PTFE) nerve conduit for controlled local delivery of a protein such as GDNF or a small molecule such as FK506. The PTFE devices were tested in a diffusion chamber, and the bioactivity of the released media was evaluated by measuring neurite growth of dorsal root ganglions (DRGs) exposed to the released drugs. The drug delivering nerve guide was able to release bioactive concentrations of FK506 or GDNF. Following these tests, optimized drug releasing nerve conduits were implanted across 10 mm sciatic nerve gaps in a BL6 yellow fluorescent protein (YFP) mouse model, where they demonstrated significant improvement in muscle mass, compound muscle action potential, and axon myelination in vivo as compared with nerve conduits without the drug. The drug delivery nerve guide could release drug for extended periods of time and enhance axon growth in vitro and in vivo.