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1.
Ann Surg ; 279(2): 231-239, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37916404

ABSTRACT

OBJECTIVE: To create a blueprint for surgical department leaders, academic institutions, and funding agencies to optimally support surgeon-scientists. BACKGROUND: Scientific contributions by surgeons have been transformative across many medical disciplines. Surgeon-scientists provide a distinct approach and mindset toward key scientific questions. However, lack of institutional support, pressure for increased clinical productivity, and growing administrative burden are major challenges for the surgeon-scientist, as is the time-consuming nature of surgical training and practice. METHODS: An American Surgical Association Research Sustainability Task Force was created to outline a blueprint for sustainable science in surgery. Leaders from top NIH-sponsored departments of surgery engaged in video and in-person meetings between January and April 2023. A strength, weakness, opportunities, threats analysis was performed, and workgroups focused on the roles of surgeons, the department and institutions, and funding agencies. RESULTS: Taskforce recommendations: (1) SURGEONS: Growth mindset : identifying research focus, long-term planning, patience/tenacity, team science, collaborations with disparate experts; Skill set : align skills and research, fill critical skill gaps, develop team leadership skills; DEPARTMENT OF SURGERY (DOS): (2) MENTORSHIP: Chair : mentor-mentee matching/regular meetings/accountability, review of junior faculty progress, mentorship training requirement, recognition of mentorship (eg, relative value unit equivalent, awards; Mentor: dedicated time, relevant scientific expertise, extramural funding, experience and/or trained as mentor, trusted advisor; Mentee : enthusiastic/eager, proactive, open to feedback, clear about goals; (3) FINANCIAL SUSTAINABILITY: diversification of research portfolio, identification of matching funding sources, departmental resource awards (eg, T-/P-grants), leveraging of institutional resources, negotiation of formalized/formulaic funds flow investment from academic medical center toward science, philanthropy; (4) STRUCTURAL/STRATEGIC SUPPORT: Structural: grants administrative support, biostats/bioinformatics support, clinical trial and research support, regulatory support, shared departmental laboratory space/equipment; Strategic: hiring diverse surgeon-scientist/scientists faculty across DOS, strategic faculty retention/ recruitment, philanthropy, career development support, progress tracking, grant writing support, DOS-wide research meetings, regular DOS strategic research planning; (5) COMMUNITY AND CULTURE: Community: right mix of faculty, connection surgeon with broad scientific community; Culture: building research infrastructure, financial support for research, projecting importance of research (awards, grand rounds, shoutouts); (6) THE ROLE OF INSTITUTIONS: Foundation: research space co-location, flexible start-up packages, courses/mock study section, awards, diverse institutional mentorship teams; Nurture: institutional infrastructure, funding (eg, endowed chairs), promotion friendly toward surgeon-scientists, surgeon-scientists in institutional leadership positions; Expectations: RVU target relief, salary gap funding, competitive starting salaries, longitudinal salary strategy; (7) THE ROLE OF FUNDING AGENCIES: change surgeon research training paradigm, offer alternate awards to K-awards, increasing salary cap to reflect market reality, time extension for surgeon early-stage investigator status, surgeon representation on study section, focused award strategies for professional societies/foundations. CONCLUSIONS: Authentic recommitment from surgeon leaders with intentional and ambitious actions from institutions, corporations, funders, and society is essential in order to reap the essential benefits of surgeon-scientists toward advancements of science.


Subject(s)
Biomedical Research , Surgeons , Humans , United States , Mentors , Faculty , Academic Medical Centers , Career Mobility , National Institutes of Health (U.S.)
2.
JAMA Surg ; 159(1): 50, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37851437
3.
Biomed Opt Express ; 14(11): 6031-6047, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-38021126

ABSTRACT

Noninvasive transabdominal fetal pulse oximetry can provide clinicians critical assessment of fetal health and potentially contribute to improved management of childbirth. Conventional pulse oximetry through continuous wave (CW) light has challenges measuring the signals from deep tissue and separating the weak fetal signal from the strong maternal signal. Here, we propose a new approach for transabdominal fetal pulse oximetry through interferometric near-infrared spectroscopy (iNIRS). This approach provides pathlengths of photons traversing the tissue, which facilitates the extraction of fetal signals by rejecting the very strong maternal signal from superficial layers. We use a multimode fiber combined with a mode-field converter at the detection arm to boost the signal of iNIRS. Together, we can detect signals from deep tissue (>∼1.6 cm in sheep abdomen and in human forearm) at merely 1.1 cm distance from the source. Using a pregnant sheep model, we experimentally measured and extracted the fetal heartbeat signals originating from deep tissue. This validated a key step towards transabdominal fetal pulse oximetry through iNIRS and set a foundation for further development of this method to measure the fetal oxygen saturation.

4.
Colorectal Dis ; 25(11): 2155-2159, 2023 11.
Article in English | MEDLINE | ID: mdl-37789561

ABSTRACT

AIM: The American College of Surgeons Committee on Cancer developed the National Accreditation Program for Rectal Cancer (NAPRC) to reduce variations in rectal cancer care, standardize clinical practice and encourage multidisciplinary approaches. The aim of this study was to analyse if accreditation achieved a higher quality of care at one hospital. METHOD: The University of California Davis Medical Center was accredited in 2019. A retrospective review of rectal adenocarcinoma patients was performed between the years 2013 and 2018. Patients presenting from 2013 to 2015 were discussed at a gastrointestinal tumour board while patients in 2018 had an accredited rectal cancer tumour board. Patients from 2016 to 2017 were excluded as the programme was still developing. Compliance to the NAPRC standards was compared between the cohorts. RESULTS: One hundred and thirty patients were evaluated, 88 (68%) in the prerectal tumour board cohort and 42 (32%) in the rectal tumour board cohort. The prerectal tumour board cohort often failed to meet attendance standards. All patients in the rectal tumour board cohort met all criteria. Similarly, clinical service compliance improved in the rectal tumour board cohort for 13 metrics, 10 of which were statistically significant. Although a high proportion of patients in both groups experienced quality surgery, i.e. complete total mesorectal excision and negative margins, the lack of complete pathological reporting in the prerectal tumour board cohort limited analysis. CONCLUSION: Multidisciplinary rectal cancer tumour boards are associated with improved compliance with recommended care by the NAPRC. Patients discussed at a rectal cancer tumour board were more likely to receive appropriate staging, coordinated care and have better clinical documentation.


Subject(s)
Rectal Neoplasms , Humans , Rectal Neoplasms/surgery , Rectal Neoplasms/pathology , Rectum/surgery , Retrospective Studies , Benchmarking , Accreditation , Neoplasm Staging
5.
Ann Surg ; 278(5): 642-646, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37796749

ABSTRACT

This paper summarizes the proceedings of the joint European Surgical Association ESA/American Surgical Association symposium on Surgical Education that took place in Bordeaux, France, as part of the celebrations for 30 years of ESA scientific meetings. Three presentations on the use of quantitative metrics to understand technical decisions, coaching during training and beyond, and entrustable professional activities were presented by American Surgical Association members and discussed by ESA members in a symposium attended by members of both associations.


Subject(s)
Mentoring , Humans , United States , Educational Status , France
6.
Fetal Diagn Ther ; 50(6): 491-500, 2023.
Article in English | MEDLINE | ID: mdl-37393899

ABSTRACT

Spina bifida is the most common congenital anomaly of the central nervous system and the first non-fatal fetal lesions to be addressed by fetal intervention. While research in spina bifida has been performed in rodent, nonhuman primate, and canine models, sheep have been a model organism for the disease. This review summarizes the history of development of the ovine model of spina bifida, previous applications, and translation into clinical studies. Initially used by Meuli et al. [Nat Med. 1995;1(4):342-7], fetal myelomeningocele defect creation and in utero repair demonstrated motor function preservation. The addition of myelotomy in this model can reproduce hindbrain herniation malformations, which is the leading cause of mortality and morbidity in humans. Since inception, the ovine models have been validated numerous times as the ideal large animal model for fetal repair, with both locomotive scoring and spina bifida defect scoring adding to the rigor of this model. The ovine model has been used to study different methods of myelomeningocele defect repair, the application of various tissue engineering techniques for neuroprotection and bowel and bladder function. The results of these large animal studies have been translated into human clinical trials including Management of Meningocele Study (MOMS) trial that established current standard of care for prenatal repair of spina bifida defects, and the ongoing trials including the Cellular Therapy for In Utero Repair of Myelomeningocele (CuRe) trial using a stem cell patch for repair. The advancement of these life savings and life-altering therapies began in sheep models, and this notable model continues to be used to further the field including current work with stem cell therapy.


Subject(s)
Meningocele , Meningomyelocele , Spinal Dysraphism , Pregnancy , Female , Animals , Sheep , Dogs , Humans , Meningomyelocele/surgery , Spinal Dysraphism/surgery , Fetus/pathology , Prenatal Care
7.
Bioact Mater ; 28: 467-479, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37408799

ABSTRACT

Implantable vascular devices are widely used in clinical treatments for various vascular diseases. However, current approved clinical implantable vascular devices generally have high failure rates primarily due to their surface lacking inherent functional endothelium. Here, inspired by the pathological mechanisms of vascular device failure and physiological functions of native endothelium, we developed a new generation of bioactive parylene (poly(p-xylylene))-based conformal coating to address these challenges of the vascular devices. This coating used a polyethylene glycol (PEG) linker to introduce an endothelial progenitor cell (EPC) specific binding ligand LXW7 (cGRGDdvc) onto the vascular devices for preventing platelet adhesion and selectively capturing endogenous EPCs. Also, we confirmed the long-term stability and function of this coating in human serum. Using two vascular disease-related large animal models, a porcine carotid artery interposition model and a porcine carotid artery-jugular vein arteriovenous graft model, we demonstrated that this coating enabled rapid generation of self-renewable "living" endothelium on the blood contacting surface of the expanded polytetrafluoroethylene (ePTFE) grafts after implantation. We expect this easy-to-apply conformal coating will present a promising avenue to engineer surface properties of "off-the-shelf" implantable vascular devices for long-lasting performance in the clinical settings.

10.
Front Pharmacol ; 14: 1125209, 2023.
Article in English | MEDLINE | ID: mdl-36937891

ABSTRACT

The lack of vascularization associated with deep burns delays the construction of wound beds, increases the risks of infection, and leads to the formation of hypertrophic scars or disfigurement. To address this challenge, we have fabricated a multi-functional pro-angiogenic molecule by grafting integrin αvß3 ligand LXW7 and collagen-binding peptide (SILY) to a dermatan sulfate (DS) glycosaminoglycan backbone, named LXW7-DS-SILY (LDS), and further employed this to functionalize collagen-based Integra scaffolds. Using a large deep burn wound model in C57/BLK6 mice (8-10 weeks old, 26-32g, n = 39), we demonstrated that LDS-modified collagen-based Integra scaffolds loaded with endothelial cells (ECs) accelerate wound healing rate, re-epithelialization, vascularization, and collagen deposition. Specifically, a 2 cm × 3 cm full-thickness skin burn wound was created 48 h after the burn, and then wounds were treated with four groups of different dressing scaffolds, including Integra + ECs, Integra + LDS, and Integra + LDS + ECs with Integra-only as the control. Digital photos were taken for wound healing measurement on post-treatment days 1, 7, 14, 21, 28, and 35. Post-treatment photos revealed that treatment with the Intgera + LDS + ECs scaffold exhibited a higher wound healing rate in the proliferation phase. Histology results showed significantly increased re-epithelialization, increased collagen deposition, increased thin and mixed collagen fiber content, increased angiogenesis, and shorter wound length within the Integra + LDS + ECs group at Day 35. On Day 14, the Integra + LDS + ECs group showed the same trend. The relative proportions of collagen changed from Day 14 to Day 35 in the Integra + LDS + ECs and Integra + ECs groups demonstrated decreased thick collagen fiber deposition and greater thin and mixed collagen fiber deposition. LDS-modified Integra scaffolds represent a promising novel treatment to accelerate deep burn wound healing, thereby potentially reducing the morbidity associated with open burn wounds. These scaffolds can also potentially reduce the need for autografting and morbidity in patients with already limited areas of harvestable skin.

11.
J Pediatr Surg ; 58(6): 1139-1144, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36966019

ABSTRACT

BACKGROUND: Leadership in academic conferences is an important factor for academic advancement. Underrepresentation of women in academic surgical conferences has been demonstrated in other subspecialties, but it has not been well-studied in pediatric surgery. METHODS: This retrospective descriptive study analyzes conference participation at 2 national pediatric surgery annual conference programs from 2003 to 2022. Moderator, speakers, and research presenter sex was collected. The primary outcome was the proportion of female participants in each of these roles. Mann-Kendall trend test was conducted to assess for significance. RESULTS: Across 29 meetings, a total of 523 sessions were examined. Overall, female participation in all roles increased from 2003 to 2022. There were statistically positive trends of female participation in leadership roles as moderator (p = 0.003) and speaker (p = 0.01), with moderator role demonstrating the largest proportional female increase over time - with a 7-fold increase from 7.1% in 2003 to 50.0% in 2022. There was also a significant increasing trend in female participation as research presenters (p < 0.01) from 25.4% to 46.4%. CONCLUSION: Gender representation in pediatric surgery conferences has improved over the last two decades. Women now represent approximately half of all participatory roles, and efforts to continue providing equal opportunities for women at pediatric surgery academic conferences should continue. LEVEL OF EVIDENCE: N/A. TYPE OF STUDY: Retrospective Descriptive.


Subject(s)
Physicians, Women , Specialties, Surgical , Child , Humans , Female , Retrospective Studies , Societies, Medical
12.
J Am Coll Surg ; 236(3): 476-483, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36729765

ABSTRACT

BACKGROUND: In 2015, the American College of Surgeons (ACS) created a new hospital improvement program to enhance the performance of pediatric care in US hospitals. The Children's Surgery Verification (CSV) Quality Improvement Program is predicated on the idea that pediatric surgical patients have improved outcomes when treated at children's hospitals with optimal resources. Achieving ACS level I CSV designation at pediatric trauma centers may lead to greater benefits for pediatric trauma patients; however, the specific benefits have yet to be identified. We hypothesize that achieving the additional designation of ACS level I CSV is associated with decreased narcotic use perioperatively and improved efficiency when managing pediatric patients with femur fractures. STUDY DESIGN: This study is a retrospective analysis of traumatic pediatric orthopaedic femur fractures treated at a verified level I pediatric trauma center before and after CSV designation (2010 to 2014 vs 2015 to 2019). Efficiency parameters, defined as time from admission to surgery, duration of surgery, and duration of hospital stay, and narcotic administration in oral morphine equivalents (OMEs) were compared. RESULTS: Of 185 traumatic femur fractures analyzed, 80 occurred before meeting ACS level I CSV criteria, and 105 occurred after. Post-CSV, there was a significant decrease in mean wait time from admission to surgery (16.64 hours pre-CSV, 12.52 hours post-CSV [p < 0.01]) and duration of hospital stay (103.49 hours pre-CSV, 71.61 hours post-CSV [p < 0.01]). Narcotic usage was significantly decreased in both the preoperative period (40.61 OMEs pre-CSV, 23.77 OMEs post-CSV [p < 0.01]) and postoperative period (126.67 OMEs pre-CSV, 45.72 OMEs post-CSV [p < 0.01]). CONCLUSIONS: Achieving ACS level I CSV designation is associated with increased efficiency and decreased preoperative and postoperative narcotic use when treating pediatric trauma patients.


Subject(s)
Fractures, Bone , Surgeons , Child , Humans , United States , Retrospective Studies , Narcotics , Trauma Centers , Hospitals, Pediatric , Femur
13.
J Pediatr Surg ; 58(5): 964-970, 2023 May.
Article in English | MEDLINE | ID: mdl-36797111

ABSTRACT

INTRODUCTION: Congenital diaphragmatic hernia (CDH) repair is an area of active research. Large defects requiring patches have a hernia recurrence rate of up to 50%. We designed a biodegradable polyurethane (PU)-based elastic patch that matches the mechanical properties of native diaphragm muscle. We compared the PU patch to a non-biodegradable Gore-Tex™ (polytetrafluoroethylene) patch. METHODS: The biodegradable polyurethane was synthesized from polycaprolactone, hexadiisocyanate and putrescine, and then processed into fibrous PU patches by electrospinning. Rats underwent 4 mm diaphragmatic hernia (DH) creation via laparotomy followed by immediate repair with Gore-Tex™ (n = 6) or PU (n = 6) patches. Six rats underwent sham laparotomy without DH creation/repair. Diaphragm function was evaluated by fluoroscopy at 1 and 4 weeks. At 4 weeks, animals underwent gross inspection for recurrence and histologic evaluation for inflammatory reaction to the patch materials. RESULTS: There were no hernia recurrences in either cohort. Gore-Tex™ had limited diaphragm rise compared to sham at 4 weeks (1.3 mm vs 2.9 mm, p = 0.003), but no difference was found between PU and sham (1.7 mm vs 2.9 mm, p = 0.09). There were no differences between PU and Gore-Tex™ at any time point. Both patches formed an inflammatory capsule, with similar thicknesses between cohorts on the abdominal (Gore-Tex™ 0.07 mm vs. PU 0.13 mm, p = 0.39) and thoracic (Gore-Tex™ 0.3 mm vs. PU 0.6 mm, p = 0.09) sides. CONCLUSION: The biodegradable PU patch allowed for similar diaphragmatic excursion compared to control animals. There were similar inflammatory responses to both patches. Further work is needed to evaluate long-term functional outcomes and further optimize the properties of the novel PU patch in vitro and in vivo. LEVEL OF EVIDENCE: Level II, Prospective Comparative Study.


Subject(s)
Hernias, Diaphragmatic, Congenital , Rats , Animals , Hernias, Diaphragmatic, Congenital/surgery , Pilot Projects , Polyurethanes , Prospective Studies , Diaphragm/surgery , Retrospective Studies
14.
Bioact Mater ; 25: 387-398, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36844366

ABSTRACT

Nanoparticle-based drug delivery systems have the potential to revolutionize medicine, but their low vascular permeability and rapid clearance by phagocytic cells have limited their medical impact. Nanoparticles delivered at the in utero stage can overcome these key limitations due to the high rate of angiogenesis and cell division in fetal tissue and the under-developed immune system. However, very little is known about nanoparticle drug delivery at the fetal stage of development. In this report, using Ai9 CRE reporter mice, we demonstrate that lipid nanoparticle (LNP) mRNA complexes can deliver mRNA in utero, and can access and transfect major organs, such as the heart, the liver, kidneys, lungs and the gastrointestinal tract with remarkable efficiency and low toxicity. In addition, at 4 weeks after birth, we demonstrate that 50.99 ± 5.05%, 36.62 ± 3.42% and 23.7 ± 3.21% of myofiber in the diaphragm, heart and skeletal muscle, respectively, were transfected. Finally, we show here that Cas9 mRNA and sgRNA complexed to LNPs were able to edit the fetal organs in utero. These experiments demonstrate the possibility of non-viral delivery of mRNA to organs outside of the liver in utero, which provides a promising strategy for treating a wide variety of devastating diseases before birth.

15.
Bioact Mater ; 20: 179-193, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35663336

ABSTRACT

Significant progress has been made in designing bone materials capable of directing endogenous cells to promote vascularized bone regeneration. However, current strategies lack regulation of the specific endogenous cell populations for vascularized bone regeneration, thus leading to adverse tissue formation and decreased regenerative efficiency. Here, we engineered a biomaterial to regulate endogenous cell adhesion and promote vascularized bone regeneration. The biomaterial works by presenting two synthetic ligands, LLP2A and LXW7, explicitly targeting integrins α4ß1 and αvß3, respectively, expressed on the surfaces of the cells related to bone formation and vascularization, such as mesenchymal stem cells (MSCs), osteoblasts, endothelial progenitor cells (EPCs), and endothelial cells (ECs). In vitro, the LLP2A/LXW7 modified biomaterial improved the adhesion of MSCs, osteoblasts, EPCs, and ECs via integrin α4ß1 and αvß3, respectively. In an adult rat calvarial bone defect model, the LLP2A/LXW7 modified biomaterial enhanced bone formation and vascularization by synergistically regulating endogenous cells with osteogenic and angiogenic potentials, such as DLX5+ cells, osteocalcin+ cells, CD34+/CD45- cells and CD31+ cells. In a fetal sheep spinal bone defect model, the LLP2A/LXW7 modified biomaterial augmented bone formation and vascularization without any adverse effects. This innovative biomaterial offers an off-the-shelf, easy-to-use, and biologically safe product suitable for vascularized bone regeneration in both fetal and adult disease environments.

17.
J Am Coll Surg ; 2022 Dec 06.
Article in English | MEDLINE | ID: mdl-36472390

ABSTRACT

BACKGROUND: This study assessed the national impact of the COVID-19 pandemic on the education of medical students assigned to surgery clerkship rotations, as reported by surgery clerkship directors(CDs). STUDY DESIGN: In the spring of 2020 and 2021, the authors surveyed 164 CDs from 144 LCME-accredited US medical schools regarding their views of the pandemic's impact on the surgery clerkship curriculum, students' experiences, outcomes, and institutional responses. RESULTS: Overall survey response rates, calculated as no. respondents/no. surveyed were 44.5%(73/164) and 50.6%(83/164) for the spring 2020 and 2021 surveys, respectively. Nearly all CDs(>95%) pivoted to virtual platforms and solutions. Most returned to some form of in-person learning by winter 2020, and pre-pandemic status by spring 2021(46%, 38/83). Students' progression to the next year was delayed by 12%(9/73), and preparation was negatively impacted by 45%(37/83). Despite these data, CDs perceived students' interest in surgical careers was not significantly affected(89% vs. 77.0%, p=0.09). Over the one-year study, the proportion of CDs reporting a severe negative impact on the curriculum dropped significantly(p<0.0001) for most parameters assessed except summative evaluations(40.3% vs. 45.7%,p=0.53). CDs(n=83) also noted the pandemic's positive impact with respect to virtual patient encounters(21.7%), didactics(16.9%), student test performance(16.9%), continuous personal learning(14.5%), engagement in the clerkship(9.6%) and student interest in surgery as a career(7.2%). CONCLUSION: During the pandemic, the severe negative impact on student educational programs lessened and novel virtual curricular solutions emerged. Student interest in surgery as a career was sustained. Measures of student competency and effectiveness of new curriculum, including telehealth, remain areas for future investigation.

18.
ACS Appl Mater Interfaces ; 14(49): 54458-54477, 2022 Dec 14.
Article in English | MEDLINE | ID: mdl-36448709

ABSTRACT

Lipid rafts are highly ordered regions of the plasma membrane enriched in signaling proteins and lipids. Their biological potential is realized in exosomes, a subclass of extracellular vesicles (EVs) that originate from the lipid raft domains. Previous studies have shown that EVs derived from human placental mesenchymal stromal cells (PMSCs) possess strong neuroprotective and angiogenic properties. However, clinical translation of EVs is challenged by very low, impure, and heterogeneous yields. Therefore, in this study, lipid rafts are validated as a functional biomaterial that can recapitulate the exosomal membrane and then be synthesized into biomimetic nanovesicles. Lipidomic and proteomic analyses show that lipid raft isolates retain functional lipids and proteins comparable to PMSC-EV membranes. PMSC-derived lipid raft nanovesicles (LRNVs) are then synthesized at high yields using a facile, extrusion-based methodology. Evaluation of biological properties reveals that LRNVs can promote neurogenesis and angiogenesis through modulation of lipid raft-dependent signaling pathways. A proof-of-concept methodology further shows that LRNVs could be loaded with proteins or other bioactive cargo for greater disease-specific functionalities, thus presenting a novel type of biomimetic nanovesicles that can be leveraged as targeted therapeutics for regenerative medicine.


Subject(s)
Placenta , Proteomics , Female , Humans , Pregnancy , Membrane Microdomains , Cell Membrane/metabolism , Proteins/metabolism , Lipids
19.
Theranostics ; 12(13): 6021-6037, 2022.
Article in English | MEDLINE | ID: mdl-35966577

ABSTRACT

Although stem cell-derived extracellular vesicles (EVs) have remarkable therapeutic potential for various diseases, the therapeutic efficacy of EVs is limited due to their degradation and rapid diffusion after administration, hindering their translational applications. Here, we developed a new generation of collagen-binding EVs, by chemically conjugating a collagen-binding peptide SILY to EVs (SILY-EVs), which were designed to bind to collagen in the extracellular matrix (ECM) and form an EV-ECM complex to improve EVs' in situ retention and therapeutic efficacy after transplantation. Methods: SILY was conjugated to the surface of mesenchymal stem/stromal cell (MSC)-derived EVs by using click chemistry to construct SILY-EVs. Nanoparticle tracking analysis (NTA), ExoView analysis, cryogenic electron microscopy (cryo-EM) and western-blot analysis were used to characterize the SILY-EVs. Fluorescence imaging (FLI), MTS assay, ELISA and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to evaluate the collagen binding and biological functions of SILY-EVs in vitro. In a mouse hind limb ischemia model, the in vivo imaging system (IVIS), laser doppler perfusion imaging (LDPI), micro-CT, FLI and RT-qPCR were used to determine the SILY-EV retention, inflammatory response, blood perfusion, gene expression, and tissue regeneration. Results:In vitro, the SILY conjugation significantly enhanced EV adhesion to the collagen surface and did not alter the EVs' biological functions. In the mouse hind limb ischemia model, SILY-EVs presented longer in situ retention, suppressed inflammatory responses, and significantly augmented muscle regeneration and vascularization, compared to the unmodified EVs. Conclusion: With the broad distribution of collagen in various tissues and organs, SILY-EVs hold promise to improve the therapeutic efficacy of EV-mediated treatment in a wide range of diseases and disorders. Moreover, SILY-EVs possess the potential to functionalize collagen-based biomaterials and deliver therapeutic agents for regenerative medicine applications.


Subject(s)
Extracellular Vesicles , Mesenchymal Stem Cells , Animals , Disease Models, Animal , Extracellular Vesicles/metabolism , Ischemia/metabolism , Mesenchymal Stem Cells/metabolism , Mice , Stem Cells , Wound Healing
20.
J Am Coll Surg ; 235(2): 195-209, 2022 08 01.
Article in English | MEDLINE | ID: mdl-35839394

ABSTRACT

BACKGROUND: A previous survey documented the severe disruption of the coronavirus disease 2019 pandemic on surgical education and trainee well-being during the initial surge and systemic lockdowns. Herein, we report the results of a follow-up survey inclusive of the 2020 to 2021 academic year. STUDY DESIGN: A survey was distributed to education leaders across all surgical specialties in summer 2021. We compared the proportion of participants reporting severe disruption in key areas with those of the spring 2020 survey. Aggregated differences by year were assessed using chi-square analysis. RESULTS: In 2021, severe disruption of education programs was reported by 14% compared with 32% in 2020 (p < 0.0001). Severe reductions in nonemergency surgery were reported by 38% compared with 87% of respondents in 2020. Severe disruption of expected progression of surgical trainee autonomy by rank also significantly decreased to 5% to 8% in 2021 from 15% to 23% in 2020 among respondent programs (p < 0.001). In 2021 clinical remediation was reported for postgraduate year 1 to 2 and postgraduate year 3 to 4, typically through revised rotations (19% and 26%) and additional use of simulation (20% and 19%) maintaining trainee promotion and job placement. In 2021, surgical trainees' physical safety and health were reported as less severely impacted compared with 2020; however, negative effects of isolation (77%), burnout (75%), and the severe impact on emotional well-being (17%) were prevalent. CONCLUSIONS: One year after the initial coronavirus disease 2019 outbreak, clinical training and surgical trainee health were less negatively impacted. Disruption of emotional well-being remained high. Future needs include better objective measures of clinical competence beyond case numbers and the implementation of novel programs to promote surgical trainee health and well-being.


Subject(s)
COVID-19 , COVID-19/epidemiology , COVID-19/prevention & control , Communicable Disease Control , Education, Medical, Graduate/methods , Follow-Up Studies , Humans , Pandemics/prevention & control , Surveys and Questionnaires
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