Implications of Patient-Provider Concordance on Treatment Recommendations for Carpal Tunnel Syndrome.

Purpose: Differences in the utilization of carpal tunnel release (CTR) by Blacks and women are well documented, but less is known regarding the impact of patient-provider concordance on treatment recommendations. To investigate this, we surveyed hand surgeons using hypothetical scenarios to evaluate variations in treatment recommendations for carpal tunnel syndrome based on patient-related factors and patient-provider concordance. Methods: Three pairs (six total) of hypothetical scenarios with clinical symptoms of carpal tunnel syndrome were created varying sex, race, and occupation. We used names as a proxy for sex and race. Occupation included manual laborers, secretaries, athletes, and retirees. American Society for Surgery of the Hand members were emailed an anonymous web-based link to participate. We used descriptive statistics to analyze the scenario-based treatment recommendations. Results: We identified 3,067 eligible members for participation; 770 surgeons responded (25%) and provided recommendations for 3,742 scenarios. For scenarios involving symptomatic patients without electrodiagnostic studies (EDS), with normal EDS, and with abnormal EDS, no difference was noted in surgeon treatment recommendations based on patients' race, sex, and occupation. Surgeons recommended EDS for 31% and 32.8% of the scenarios with Black female and White male patients, respectively, who did not have EDS at presentation and CTR for 32.3% and 33% of White females and Black males with normal EDS, respectively. Among retired Black female and White male patients older than 80 years of age with abnormal EDS, surgeons recommended CTR in 89.9% and 89.3% of them, respectively. For patient-provider racially concordant pairs, White surgeons recommended CTR to a similar proportion of Black and White hypothetical patients; however, Black surgeons recommended CTR to a greater proportion of patients with Black-sounding names. Conclusions: We found that surgeon treatment recommendation was not associated with patient race, sex, or occupation; however, differences did emerge based on patient-provider racial concordance, suggesting that alignment of patient and provider identities may influence treatment recommendations. Type of study/level of evidence: Prognostic III.

Early Lessons From Implementation of Holistic Review for Pediatric Surgery Fellowship Applicants.

PURPOSE: Holistic review (HR) considers applicants' unique identities and experiences rather than focusing on academic metrics. Though several residency programs have demonstrated increases in women and those underrepresented in medicine (URiM), this is the first study to examine HR in pediatric surgery (PS). METHODS: Using a retrospective review of applicants, demographic, academic, and non-academic metrics of traditional review (TR) [2015-2017] were compared to HR [2018-2022]. HR initiatives include expansion of faculty reviewers, implementation of a pre-screening rubric, and greater prioritization of non-academic factors. Chi-squared/Fisher's exact tests, Wilcoxon rank-sum tests, and two sample z-test for proportions were used where appropriate. RESULTS: For 635 applicants (TR: 268, HR: 367), the proportion offered interviews in the TR and HR cohorts were similar (31.7 vs 36%, p = 0.30). Candidates selected for interview pre- and post-HR most commonly graduated from residency programs affiliated with PS fellowships (56.5 vs 50%, p = 0.65). After HR implementation, no change in proportion of women interviewees (TR: 52.9 vs HR: 54.5%, p = 0.93) was observed. Though URiM residents applying to PS remained consistently low (TR: 14.6 vs HR: 10.9%, p = 0.21), significantly more received interviews with HR (30.8 vs 42.5%, p = 0.001). The median number of peer-review publications per interviewee increased (17 vs 22, p = 0.02) as did non-academic achievements (leadership, service, athletic awards, etc.) per applicant (1.0 vs 1.5, p = 0.104), though the latter did not reach significance, demonstrating similar qualification of interviewees in HR and TR. CONCLUSION: Holistic review of PS fellowship applications increased the proportion of URiM interviewees, despite a persistently low URiM proportion in the applicant pool. Furthermore, implementing HR did not sacrifice the caliber of interviewees, as publications and non-academic achievements increased by over 25% in the HR cohort. LEVEL OF EVIDENCE: IV.

Decision for Carpal Tunnel Surgery: High-deductible Health Plans versus Traditional Health Plans.

Background: Delay in surgical treatment for carpal tunnel syndrome (CTS) may result in long-term decreased functional outcomes. Few investigators have examined the relationship between type of health insurance plan and time to definitive treatment of CTS following diagnosis. We investigated the relationship between insurance type, treatment decision, and the time between diagnosis and surgery across groups. Methods: This was a retrospective cohort study using the MarketScan Commercial Claims and Encounters Database 2011-2020. We used χ2 tests, linear regression, and logistic regression models to analyze demographic data and the time lag interval between CTS diagnosis and treatment. Results: Overall, 28% of high-deductible health plan (HDHP) patients underwent carpal tunnel release, compared with 20% of traditional insurance patients (P < 0.001). HDHPs are defined by the internal revenue service as a deductible of $1400 for an individual or $2800 for a family per year. The odds of undergoing surgery versus no treatment for HDHP patients were 47% higher than traditional patients (P < 0.001). Among the patients who underwent surgery, HDHP patients underwent surgery 65 days earlier on average following diagnosis compared with traditional patients (P < 0.001). Conclusions: Patients with HDHPs who receive a diagnosis of CTS are more likely to undergo surgery, with a shorter time lag between diagnosis and surgery. The results from this study call attention to differences in surgical decision-making between patients enrolled in different insurance plans.

A Historical Review of Racial, Ethnic, and Gender Diversity in Plastic Surgery at the University of Michigan.

In this article, we examine the 60-year history of diversity efforts within the Section of Plastic Surgery at the University of Michigan (UofM) in the context of national trends. We describe the experiences of pioneering Underrepresented in Medicine (URiM) and female graduates of the program. James Norris, MD, and Christine Sullivan, MD, were the first URiM and female graduates from UofM in 1974 and 1989, respectively. Currently, women constitute over one-half the plastic surgery trainees at UofM, but URiM trainee representation remains limited. Dr. Adeyiza Momoh and Dr. Amy Alderman were the first URiM and female faculty members hired in 2011 and 2004, respectively. At present, there are four URiM and seven female faculty members in the Section. With a shared vision, supportive leadership, and motivation to change, faculty diversity has increased substantially. Additional strategies, including ongoing pipeline programs in medicine and science for URiM and women, are needed to further increase workforce diversity in plastic surgery.

An Analysis of Treatment Choices among White and African American Medicaid Patients with Carpal Tunnel Syndrome.

BACKGROUND: Carpal tunnel syndrome (CTS) is the most common compressive neuropathy and has severe long-term effects on hand function if surgery is delayed significantly following diagnosis. The authors investigated the timespan between diagnosis and surgical intervention for carpal tunnel syndrome among African American and White patients on Medicaid. METHODS: Using the MarketScan Truven Database Medicaid Supplement 2009 to 2020, the authors identified patients with CTS. Demographic data and time intervals between diagnosis and treatment were collected and analyzed using chi-square test and regression models. RESULTS: A total of 361,942 African American and White Medicaid patients with a diagnosis of CTS were included in the study. Overall, 21.4% of White patients compared with 13.6% of African American patients chose surgery as their first and only option ( P < 0.001). A greater proportion of White patients underwent surgery less than 6 months after diagnosis compared with African Americans (75.5% and 67.7%, respectively; P < 0.001). African American women underwent surgery at a significantly lower rate compared with White women (13.8% and 21.8%, respectively); P < 0.001). Despite the increase in rates of surgery among both groups, the gap in use of surgery widened from a 6.6% difference in 2009 to a difference of 9.5% in 2020 between racial groups. CONCLUSIONS: African American race and female sex are significantly correlated with choice of treatment and time to surgery among Medicaid patients with CTS. Identification of the relationship between health care disparities and the decision to undergo surgery is the first step in the development of strategies to mitigate underuse of this quality-of-life-improving procedure.

Recognition and Respect: Contextualizing the History and Contributions of Black American Plastic Surgeons.

Recently, there has been heightened interest in the history of Black American plastic surgeons and their contributions to the field of plastic and reconstructive surgery (PRS). Despite the increased awareness and attention toward the lack of racial and ethnic diversity of the PRS workforce, the history of how PRS became one of the most ethnically segregated surgical specialties remains unexplored. Here, we outline the various political and cultural factors that contributed to the exclusion of Black practitioners from American PRS professional societies. This work contextualizes the rise of American PRS within the Jim Crow era and highlights the cultural significance of reconstructive procedures performed in the treatment of disfigured soldiers. Through this lens, we identify circumstances where Black surgeons were systematically denied opportunities to participate in the emerging specialty. Despite these barriers, we demonstrate how Black physicians established informal networks for professional advancement and shed light on several previously unrecognized contributions to PRS from Black surgeons. In addition, we explore how the inclusion of Black voices in PRS sparked a paradigm shift in the treatment of non-White patients that expanded the cosmetic marketplace in ways that remain significant today. Finally, we situate the ongoing disparities in Black representation in PRS within a broader historical narrative and illustrate how the stories we tell about our past continue to shape the future of our field.

Resource Utilization and the Use of Bone Stimulators among Operatively and Nonoperatively Managed Scaphoid Nonunion Patients.

The prevalence of bone stimulator use among nonoperatively and operatively managed scaphoid nonunion patients is unknown. We hypothesize that bone stimulators are a relatively underutilized treatment for scaphoid nonunion patients. Methods: We used the 2009-2017 Truven Marketscan Research Databases to identify patients with closed scaphoid fractures and performed an analysis of variance test to determine resource utilization and bone stimulator use among these patients. Results: A total of 36,611 patients with scaphoid fractures were identified: 30,143 were managed nonoperatively and 6468 were managed operatively. Nonunion was diagnosed in 500 (1.66%) nonoperatively and in 1211 (19%) operatively managed patients. Bone stimulators were used in less than 2% of nonoperatively and operatively managed scaphoid nonunion patients. Conclusion: Lack of trust in the technology and heterogenous (and occasionally burdensome) requirements for insurance approval are barriers to bone stimulator use; however, surgeons should examine how this technology may fit into the treatment algorithm for these difficult cases.

An Analysis of the Impact of Timing and Technique on Outcomes after Surgery for Distal Radius Fractures: The Wrist and Radius Injury Surgical Trial Collaborative Study.

BACKGROUND: Surgical treatment of closed distal radius fractures varies based on treatment, surgeon schedule, and patient preferences. The authors examined how timing and technique impact surgeon-perceived procedural difficulty and quality of reduction, outcomes, and complications. METHODS: This was a retrospective study of participants in the randomized, multicenter Wrist and Radius Injury Surgical Trial with isolated unstable distal radius fractures. Participants were randomized to treatment with a volar locking plate system, closed reduction and percutaneous pinning, or external fixation. The authors analyzed surgeon-perceived procedural difficulty and reduction quality based on time to operation. RESULTS: Of 184 participants, 88 underwent surgery less than 7 days after fracture (mean, 4.6 days) and 96 underwent surgery at more than 7 days after fracture (mean, 12.3 days). Surgery performed at more than 7 days was rated more difficult versus surgery at less than 7 days [4.6 versus 3.8 of 10 (1 = easiest); p = 0.05]. When the volar locking plate technique was performed, there was no difference in surgeon-perceived difficulty or reduction quality between the groups; however, surgeons performing closed reduction and percutaneous pinning more than 7 days after injury reported greater procedure difficulty (4.1 versus 2.9; p = 0.05) and poorer reduction quality compared to less than 7 days (7.2 versus 8.1; p = 0.03). Participants who underwent surgery at less than 7 days scored 8 and 7 points greater on the Michigan Hand Outcomes Questionnaire Satisfaction (p = 0.05) and Activities of Daily Living (p = 0.03) domains, respectively. CONCLUSIONS: Surgery performed less than 7 days after fracture leads to better surgeon-perceived reduction quality and less procedural difficulty. If surgery cannot be performed before 7 days, the authors recommend patients undergo treatment with the volar locking plate system, given the comparable level of surgeon-perceived procedural difficulty and reduction quality when surgery was performed less than 7 days after injury. CLINICAL QUERSTION/LEVEL OF EVIDENCE: Therapeutic, III.

Epidemiology of Upper Extremity Firearm Injuries among Major Trauma Hospitals in the United States.

BACKGROUND: As many as 34 percent of nonfatal firearm injuries involve the upper extremity. Although not lethal, these injuries cause substantial morbidity. The authors conducted an epidemiologic study characterizing upper extremity firearm-related injuries presenting to U.S. trauma centers over a 10-year period. METHODS: The authors used the National Trauma Databank from 2007 to 2017 to identify isolated upper extremity firearm-related injuries. Descriptive statistics were performed to characterize patient demographic data, firearm type, extremity injury patterns, treatments received, hospital length of stay, and regional variation. RESULTS: The authors identified 48,254 upper extremity firearm-related injuries. The patients were largely male patients (85 percent), and over half were between the ages of 20 and 39 years. Handguns (34 percent) were the most frequently used firearm. Shoulder and upper arm were the most frequently injured areas (54 percent); however, 18 percent of patients injured two or more areas. Patients were most often treated at university hospitals (59 percent) with Level I or II trauma designation. Seventy percent were admitted and/or taken directly to the operating room. The mean hospital length of stay was 3 days. Payer mix among these patients was variable: Medicaid, 20 percent; private insurance, 20 percent; and self-pay, 29 percent. CONCLUSIONS: Upper-extremity firearm injuries are resource intensive, with three-quarters of patients requiring operative intervention and/or hospitalization. Level I and II trauma centers were the site of care for the majority of patients. Targeted gun policy reform and prevention measures directed toward at-risk groups have the potential to limit the unnecessary morbidity and costs associated with these injuries.

Regenerative Peripheral Nerve Interfaces for the Management of Symptomatic Hand and Digital Neuromas.

Painful neuromas result from traumatic injuries of the hand and digits and cause substantial physical disability, psychological distress, and decreased quality of life among affected patients. The regenerative peripheral nerve interface (RPNI) is a novel surgical technique that involves implanting the divided end of a peripheral nerve into a free muscle graft for the purposes of mitigating neuroma formation and facilitating prosthetic limb control. The RPNI is effective in treating and preventing neuroma pain in major extremity amputations. The purpose of this study was to determine if RPNIs can be used to effectively treat neuroma pain following partial hand and digital amputations. We retrospectively reviewed the use of RPNI to treat symptomatic hand and digital neuromas at our institutions. Between November 2014 and July 2019, we performed 30 therapeutic RPNIs on 14 symptomatic neuroma patients. The average patient follow-up was 37 weeks (6-128 weeks); 85% of patients were pain-free or considerably improved at the last office visit. The RPNI can serve as a safe and effective surgical solution to treat symptomatic neuromas after hand trauma.

Closed Metacarpal Neck Fractures: A Review of Resource Use in Operative and Nonoperative Management.

BACKGROUND: Closed metacarpal neck fractures are extremely common. The authors investigated resource use among those managed operatively versus nonoperatively. They hypothesized that considerable use of services and costs are incurred with nonoperative management. METHODS: The authors used the 2009 to 2017 Truven Marketscan Research Database to identify patients with closed metacarpal neck fractures and divided them into operative and nonoperative groups. They examined resource use, including imaging, clinic visits, surgery, and occupational therapy sessions, and performed a chi-square analysis of patient demographic data and resources used. RESULTS: Of 125,610 patients identified, 46,845 met inclusion criteria: nonoperative, n = 45,067 (96.2 percent); and operative, n = 1778 (3.8 percent). The operative group comprised percutaneous fixation (62 percent) and open reduction and internal fixation (38 percent) patients. Nonoperative patients had the greatest mean number of clinic visits, with 1.7 per patient, compared to 1.2 for both percutaneous fixation and open reduction and internal fixation patients (p < 0.001). For nonoperative patients, one to two radiographs (beyond the index radiograph) were obtained, and they had 2.9 occupational therapy sessions; in the operative group, two to three radiographs were obtained, and they had three to four occupational therapy sessions (p < 0.001). Mean total costs were $2406 per patient for percutaneous fixation, $3092 per patient for open reduction and internal fixation, $546 per patient for closed reduction, and $261 per patient for no intervention. CONCLUSIONS: Nonoperative management of closed metacarpal neck fracture has lower costs without the associated operating room, surgeon, and service fees; however, patient care remains resource intensive with the use of imaging, clinic visits, and occupational therapy. Shifts in the authors' treatment paradigm, including judicious use of services, will result in significant health care savings.

Postoperative follow-up time and justification in prospective hand surgery research: a systematic review.

We systematically reviewed prospective studies for five hand procedures to analyse postoperative follow-up time, clinical or radiographic plateau, and whether the authors provide justification for times used. Demographic data, outcomes and mean follow-up were analysed. A total of 188 articles met our inclusion criteria. The mean postoperative follow-up time among these studies were carpal tunnel release, 21 months (range 1.5-111); cubital tunnel release, 27 months (2.5-46); open reduction and internal fixation for the distal radius fracture, 24 months (3-120); thumb carpometacarpal joint arthroplasty, 64 months (8.5-228); and flexor tendon repair, 25 months (3-59). Authors provided justification for follow-up intervals in 10% of these reports. We conclude that most prospective clinical studies in hand surgery do not properly justify follow-up length. Clinically unnecessary follow-up is costly without much benefit. In prospective research, we believe justified postoperative follow-up is essential, based on expected time to detect clinical plateau, capture complications and determine the need for secondary surgery.Level of evidence: III.

Pre-injury activity predicts outcomes following distal radius fractures in patients age 60 and older.

INTRODUCTION: One out of every 5 elderly patients will suffer a distal radius fracture and these injuries are often related to poor bone health. Several surgical subspecialties have demonstrated that pre-injury activity level can impact patient outcomes. To determine the importance of physical activity, we examined the relationship between pre-injury activity and patient-reported and functional outcomes among fracture patients. METHODS: This is a retrospective analysis of prospectively collected data from participants enrolled in the Wrist and Radius Injury Surgical Trial (WRIST) from April 10, 2012 to December 31, 2016. This study included 304 adults, 60 years or older with isolated unstable distal radius fractures; 187 were randomized to one of three surgical treatments and 117 opted for casting. Participants opting for surgery were randomized to receive volar locking plate, percutaneous pinning, or external fixation. Participants who chose not to have surgery were treated with casting. All participants were stratified prior to analysis into highly and less-active groups based on pre-injury Rapid Assessment of Physical Activity Scores. RESULTS: 280 patients had 12-month assessments of outcomes. Highly active participants scored 8 and 5 points greater on the Michigan Hand Questionnaire at 6 weeks and 3 months respectively, p<0.05. Highly active participants demonstrated greater grip strength at the 3-month (p = 0.017) and 6-month (p = 0.007) time-points. Highly active participants treated with volar locking plate scored 10+ points greater on the Michigan Hand Questionnaire compared to the less-active group at the 6-week (p = 0.032), 3-month (p = 0.009) and 12-month (0.004) time points, with an effect size larger than 0.50, suggesting pre-injury level of activity had a significant clinical impact. CONCLUSIONS: Higher levels of pre-injury activity are predictive of patient-reported and functional outcomes following distal radius fracture. Because of the greater PROs, the early mobility and lower risk of hardware infection reported in the literature, volar plating is preferable to other treatments for highly active patients who request and meet indications for surgery. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01589692.

An In-Depth Review of Physician Reimbursement for Digit and Thumb Replantation.

PURPOSE: To examine physician and hospital reimbursement for digit and thumb replantation compared with revision amputation. METHODS: Using the 2009-2016 Truven Health MarketScan Research Databases, we identified patients with a digit or thumb amputation. Following application of our inclusion and exclusion criteria, we divided patients into replantation and revision amputation groups. We extracted the mean physician and hospital reimbursement associated with each patient encounter. For comparison, we examined the work Relative Value Unit (wRVU) and Medicare Physician Fee Schedule (MPFS) for the respective procedures in addition to several common hand surgery procedures. RESULTS: We identified 51,716 patients. Following application of our inclusion and exclusion criteria, 219 replantation and 6,209 revision amputation patients were included in our analysis. For replantation, the mean physician and hospital reimbursements ranged from $3,938 to $7,753 and $30,683 to $56,256, respectively. For revision amputation, the mean physician and hospital reimbursements ranged from $1,030 to $1,206 and $2,877 to $4,188, respectively. On multivariable analysis, hospitals performing replantation earned $37,788 more per case compared with revision amputation. Using the wRVU and MPFS data, we determined that replantation reimburses at $78/wRVU compared with higher earnings for revision amputation ($108), carpal tunnel release ($101), cubital tunnel release ($97), trigger finger release ($116), open reduction and internal fixation (ORIF) distal radius fracture ($87), flexor tendon repair ($98), extensor tendon repair ($122), repair of digital nerve ($89), and ORIF articular fracture ($82), respectively. CONCLUSIONS: Low physician reimbursement for replantation compared with less complex hand procedures makes it difficult to recruit and retain hand surgeons for this purpose. By understanding the wRVU and MPFS system, hand surgeons and professional societies can explore ways to promote change in the way replantation is valued by the Centers for Medicare and Medicaid Services (CMS) as well as by hospital administrators. TYPE OF STUDY/LEVEL OF EVIDENCE: Economic/Decision Analysis III.

Microstructured hydrogel scaffolds containing differential density interfaces promote rapid cellular invasion and vascularization.

INTRODUCTION: Insufficient vascularization of currently available clinical biomaterials has limited their application to optimal wound beds. We designed a hydrogel scaffold with a unique internal microstructure of differential collagen densities to induce cellular invasion and neovascularization. METHODS: Microsphere scaffolds (MSS) were fabricated by encasing 1% (w/v) type 1 collagen microspheres 50-150 µm in diameter in 0.3% collagen bulk. 1% and 0.3% monophase collagen scaffolds and Integra® disks served as controls. Mechanical characterization as well as in vitro and in vivo invasion assays were performed. Cell number and depth of invasion were analyzed using Imaris™. Cell identity was assessed immunohistochemically. RESULTS: In vitro, MSS exhibited significantly greater average depth of cellular invasion than Integra® and monophase collagen controls. MSS also demonstrated significantly higher cell counts than controls. In vivo, MSS revealed significantly more cellular invasion spanning the entire scaffold depth at 14 days than Integra®. CD31+ expressing luminal structures suggestive of neovasculature were seen within MSS at 7 days and were more prevalent after 14 days. Multiphoton microscopy of MSS demonstrated erythrocytes within luminal structures after 14 days. CONCLUSION: By harnessing simple architectural cues to induce cellular migration, MSS holds great potential for clinical translation as the next generation dermal replacement product. STATEMENT OF SIGNIFICANCE: Large skin wounds require tissue engineered dermal substitutes in order to promote healing. Currently available dermal replacement products do not always adequately incorporate into the body, especially in complex wounds, due to poor neovascularization. In this paper, we present a hydrogel with an innovative microarchitecture that is composed of dense type I collagen microspheres suspended in a less-dense collagen bulk. We show that cell invasion into the scaffold is driven solely by mechanical cues inherent within this differential density interface, and that this induces robust vascular cell invasion both in vitro and in a rodent model. Our hydrogel performs favorably compared to the current clinical gold standard, Integra®. We believe this hydrogel scaffold may be the first of the next generation of dermal replacement products.

Breast Cancer Knowledge and Decisions Made for Contralateral Prophylactic Mastectomy: A Survey of Surgeons and Women in the General Population.

BACKGROUND: Decisions made to undergo contralateral prophylactic mastectomy, in women at low risk for bilateral disease, are often attributed to a lack of knowledge. This study examines the role knowledge plays in determining surgical treatment for unilateral breast cancer made by laywomen and surgeons for themselves or loved ones. METHODS: The study cohort had three groups: (1) laywomen in the general population, (2) breast surgeons, and (3) plastic surgeons. Laywomen were recruited using Amazon Mechanical Turk Crowd Sourcing. Breast and plastic surgeons from nine states were sent electronic surveys. Demographic and contralateral prophylactic mastectomy-specific data on decisions and knowledge were collected and analyzed. RESULTS: Surveys from 1333 laywomen, 198 plastic surgeons, and 142 breast surgeons were analyzed. A significantly greater proportion of laywomen in the general population favored contralateral prophylactic mastectomy (67 percent) relative to plastic (50 percent) and breast surgeons (26 percent) (p < 0.0001). Breast surgeons who chose contralateral prophylactic mastectomy were younger (p = 0.044) and female (0.012). On assessment of knowledge, 78 percent of laywomen had a low level of breast cancer knowledge. Laywomen with higher levels of breast cancer knowledge had lower odds of choosing contralateral prophylactic mastectomy (OR, 0.37; 95 percent CI, 0.28 to 0.49). CONCLUSIONS: Fewer women are likely to make decisions in favor of contralateral prophylactic mastectomy with better breast cancer-specific education. A knowledge gap likely explains the lower rates with which surgeons choose contralateral prophylactic mastectomy for themselves or loved ones; however, some surgeons who were predominantly young and female favor contralateral prophylactic mastectomy. Improving patient education on surgical options for breast cancer treatment is critical, with well-informed decisions as the goal.

Fabrication of capillary-like structures with Pluronic F127® and Kerria lacca resin (shellac) in biocompatible tissue-engineered constructs.

The fabrication of large cellular tissue-engineered constructs is currently limited by an inability to manufacture internal vasculature that can be anastomosed to the host circulatory system. Creation of synthetic tissues with microvascular networks that adequately mimic the size and density of in vivo capillaries remains one of the foremost challenges within tissue engineering, as cells must reside within 200-300 µm of vasculature for long-term survival. In our previous work, we used a sacrificial microfibre technique whereby Pluronic® F127 fibres were embedded and then sacrificed within a collagen matrix, leaving behind a patent channel, which was subsequently seeded with endothelial and smooth muscle cells, forming a neointima and neomedia. We now have extended our technique and describe two approaches to synthesize a biocompatible tissue-engineered construct with macro-inlet and -outlet vessels, bridged by a dense network of cellularized microvessels, recapitulating the hierarchical organization of an arteriole, venule and capillary bed, respectively. Copyright © 2016 John Wiley & Sons, Ltd.

A Novel Three-Dimensional Platform to Investigate Neoangiogenesis, Transendothelial Migration, and Metastasis of MDAMB-231 Breast Cancer Cells.

BACKGROUND: A crucial step in the progression of cancer involves the transendothelial migration of tumor cells into the bloodstream and invasion at distant sites. Most in vitro models of malignant cell behavior do not account for the presence of and interaction with vascular cells. Three-dimensional platforms to further explore the factors responsible for metastatic cellular behavior are under intensive investigation. METHODS: Hydrogels with encapsulated MDAMB-231 breast cancer cells were fabricated with a central microchannel. The microchannel was lined with a co-culture of human umbilical vein endothelial cells and human aortic smooth muscle cells. For comparison, co-culture-seeded microchannels without breast cancer cells (MDAMB-negative) were fabricated. RESULTS: After 7 and 14 days, the endoluminal lining of encapsulated MDAMB-231 co-culture-seeded microchannels demonstrated aberrant endothelial cell and smooth muscle cell organization and breast cancer cell transendothelial migration. MDAMB-231 cells performed matrix remodeling, forming tumor aggregates within the bulk, migrating preferentially toward the hydrogel "neovessel." In contrast, MDAMB-negative constructs demonstrated maintenance of an intact endoluminal lining composed of endothelial cells and smooth muscle cells that organized into discrete layers. Furthermore, the thicknesses of the endoluminal lining of MDAMB-negative constructs were significantly greater than encapsulated MDAMB-231 co-culture-seeded constructs after 7 and 14 days (p = 0.012 and p < 0.001, respectively). CONCLUSION: The authors have created a powerful tool that may have tremendous impact on furthering our understanding of cancer recurrence and metastasis, shedding light on these poorly understood phenomena.

Long-Term Morphological and Microarchitectural Stability of Tissue-Engineered, Patient-Specific Auricles In Vivo.

Current techniques for autologous auricular reconstruction produce substandard ear morphologies with high levels of donor-site morbidity, whereas alloplastic implants demonstrate poor biocompatibility. Tissue engineering, in combination with noninvasive digital photogrammetry and computer-assisted design/computer-aided manufacturing technology, offers an alternative method of auricular reconstruction. Using this method, patient-specific ears composed of collagen scaffolds and auricular chondrocytes have generated auricular cartilage with great fidelity following 3 months of subcutaneous implantation, however, this short time frame may not portend long-term tissue stability. We hypothesized that constructs developed using this technique would undergo continued auricular cartilage maturation without degradation during long-term (6 month) implantation. Full-sized, juvenile human ear constructs were injection molded from high-density collagen hydrogels encapsulating juvenile bovine auricular chondrocytes and implanted subcutaneously on the backs of nude rats for 6 months. Upon explantation, constructs retained overall patient morphology and displayed no evidence of tissue necrosis. Limited contraction occurred in vivo, however, no significant change in size was observed beyond 1 month. Constructs at 6 months showed distinct auricular cartilage microstructure, featuring a self-assembled perichondrial layer, a proteoglycan-rich bulk, and rounded cellular lacunae. Verhoeff's staining also revealed a developing elastin network comparable to native tissue. Biochemical measurements for DNA, glycosaminoglycan, and hydroxyproline content and mechanical properties of aggregate modulus and hydraulic permeability showed engineered tissue to be similar to native cartilage at 6 months. Patient-specific auricular constructs demonstrated long-term stability and increased cartilage tissue development during extended implantation, and offer a potential tissue-engineered solution for the future of auricular reconstructions.