Biology subjects

Rodriguez, E. D.

Publications and source records attributed to Rodriguez, E. D..

4 recordsLinked to original sources

bioRxiv2025

Preservation Strategies for Vascularized Composite Allotransplantation: An Updated Systematic Review of a Rapidly Expanding Field

BackgroundVascularized composite allotransplantation has become a viable reconstructive option for selected patients, but preservation remains a major barrier to broader clinical application. Static cold storage is the current gold standard, yet ischemia reperfusion injury and limited preservation times restrict its effectiveness. Recent advances in machine perfusion and subzero non-freezing storage (or supercooling) have prompted renewed interest in optimizing graft viability. MethodsFollowing PRISMA guidelines, we systematically searched PubMed, EMBASE, and Cochrane, covering studies published from June 2022 through August 2025 for studies on ex vivo preservation of vascularized composite allotransplantations. Eligible articles included original studies in English evaluating postharvest, pretransplant preservation strategies. Data extracted were study design, preservation methods, perfusates, and primary outcomes. Risk of bias was assessed using SYRCLE for animal studies and JBI for human/cadaver studies. ResultsSeventeen studies met inclusion criteria: one on static cold storage, thirteen on machine perfusion, and three on supercooling. Static cold storage research has declined, with the only recent study investigating sub-normothermic machine perfusion as a recovery adjunct. Machine perfusion studies focused on optimization of perfusion parameters, perfusate composition, and circuit design. Red blood cell-based perfusates remained common, but alternative oxygen carriers such as polymerized hemoglobin-based oxygen carrier-201 and dextran oxygen microcarriers showed promise despite edema-related challenges. Supercooling studies demonstrated feasibility of multi-day preservation in rodent and porcine models. Overall, risk of bias was high or unclear across animal studies, mainly due to selection and performance bias, whereas the single human ex vivo study showed low risk of bias. ConclusionsThe field of vascularized composite allograft preservation is expanding rapidly, with machine perfusion and supercooling emerging as the most promising strategies to extend graft viability beyond the limits of static cold storage. However, translation to clinical setting remains limited by small preclinical studies, methodological heterogeneity, and the paucity of functional and immunologic endpoints. Standardized protocols, robust large-animal models, and eventual human feasibility trials are needed to establish clinically applicable preservation strategies. Level of evidence: IV

bioengineering↗

bioRxiv2024

Pre-treatments of Ex vivo Vascularized Composite Allografts: A Scoping Review

PURPOSEThe various physiological profiles comprising vascularized composite allografts (VCAs) pose unique challenges to preservation. Minimizing ischemia, reperfusion injury, and rejection remains a primary focus of graft pre-treatments (PTs). Currently, the gold standard PT consists of flushing the graft and placing it in static cold storage in the University of Wisconsin solution. With this method, graft viability is limited to four to six hours. Prolonging this time limit will increase donor allocation radius, access to care, and positive patient outcomes. We aimed to evaluate novel PTs that could potentially enhance and lengthen VCA viability. METHODSFollowing PRISMA guidelines, we conducted a comprehensive literature search of Embase, Cochrane, and PubMed. Studies had to be published prior to June 15, 2022. PTs had to target cell physiology, rather than immunogenicity. We extracted data including study design, PT details, evaluation metrics, and outcomes. RESULTSWe identified thirteen studies, categorized into three groups: solution-based alterations to the gold standard, ex vivo perfusion, and other novel techniques. The incorporation of hydrogen sulfide and Perfadex as solutions in the gold standard protocol demonstrated a six-day delay in rejection and limited reperfusion injury markers, respectively. In one ex vivo perfusion study, after 24 hours of PT and 12 hours post-transplant, VCA muscle contractility remained close to normal. The gold standard PT did not demonstrate the same success. However, graft weight gain, up to 50% of baseline among the articles reviewed, is a prominent side effect of perfusion. Another technique, cryopreservation, displayed 90% graft failure by venous thrombosis, despite high free graft viability following two weeks of storage. CONCLUSIONSThis study of pre-treatment modalities found a variety of encouraging preservation techniques for grafts with high levels of tissue diversity. Ex vivo perfusion dominated PT innovation with promising results in preserving the viability and functionality of muscle, which is central to the restoration of movement. Future studies are necessary to evaluate long-term graft outcomes and to optimize PT protocols for extended preservation times to ensure clinical relevance.

systems biology↗

bioRxiv2022

Evolution of a Plastic Surgery Summer Research Program

BackgroundEarly surgical exposure and research fellowships have been independently shown to influence medical students specialty choice, increase academic productivity, and impact residency match. However, to our knowledge there is no published guidance on the implementation of formal plastic surgery summer research programs for first year medical students. We present our institutional experience developing a plastic surgery summer research program over seven years (2013-2020) in an effort to inform program development at other institutions. We hypothesized that this early, formal exposure could spark interest in pursuing research activities throughout medical school and residency. MethodsFrom 2013 to 2016, a sole basic science research arm existed. In 2017, a clinical research arm was introduced, with several supplemental activities including structured surgical skills sessions. A formalized selection process was instituted in 2014. Participant feedback was analyzed on a yearly basis. Long-term outcomes included continued research commitment, productivity, and residency match. ResultsThe applicant pool has reached 96 applicants in 2019, with 85% from outside institutions. Acceptance rate reached 7% in 2020. With adherence to a scoring rubric for applicant evaluation, good to excellent interrater reliability was achieved (ICC = 0.75). Long-term outcomes showed that on average per year, 28% of participants continued departmental research activities and 29% returned for dedicated research. Upon finishing medical school, participants had a mean of 6.9{+/-}4.0 peer-reviewed publications. 62% of participants matched into a surgical residency program, with 54% in integrated plastic surgery. ConclusionsA research program designed for first year medical students interested in plastic surgery can achieve academic goals. Students are provided with mentorship, networking opportunities, and tools for self-guided learning and career development.

scientific communication and education↗

bioRxiv2022

Inhibition of the IL-17A axis Protects against Immune-related Adverse Events while Supporting Checkpoint Inhibitor Anti-tumor Efficacy

Checkpoint inhibitor (ICI) immunotherapy leverages the bodys own immune system to attack cancer cells but leads to unwanted autoimmune side effects in up to 60% of patients. Such immune related adverse events (IrAE) may lead to treatment interruption, permanent organ dysfunction, hospitalization and premature death. Thyroiditis is one of the most common IrAE, but the cause of thyroid IrAE remains unknown. Here we present a novel mouse model in which checkpoint inhibitor therapy leads to multi-organ autoimmune infiltrates and show that activation and infiltration of Type 3 immune cells including IL17A+ ROR{gamma}t+ CD4+ (T helper 17 or Th17) and gamma delta 17 ({gamma}{delta}T17) T cells promote thyroid IrAE development. IL-17A+ T cells were similarly found in thyroid specimens from cancer patients treated with ICI who developed thyroid IrAE. Furthermore, antibody-based inhibition of IL-17A, a clinically available therapy, significantly reduced thyroid IrAE development in ICI-treated mice. Finally, combination of IL-17A neutralization with ICI treatment in multiple tumor models did not reduce ICI anti-tumor efficacy. These studies suggest that targeting Th17 and {gamma}{delta}17 function may reduce IrAE without impairing ICI anti-tumor efficacy and may be a generalizable strategy to address IL17-mediated IrAE.

immunology↗