Papers by Anthony Sandler
Frontiers in Immunology
IntroductionThe combination of Myc-suppressed whole tumor cells with checkpoint inhibitors target... more IntroductionThe combination of Myc-suppressed whole tumor cells with checkpoint inhibitors targeting CTLA-4 and PD-L1 generates a potent therapeutic cancer vaccine in a mouse neuroblastoma model. As immunotherapies translate from pre-clinical to clinical trials, the potential immune-related adverse events (irAEs) associated with induction of potent immunity must be addressed. The CD24-Siglec 10/G interaction is an innate checkpoint that abrogates inflammatory responses to molecules released by damaged cells, but its role in cancer immunology is not well defined. We investigate irAEs of an effective whole cell neuroblastoma vaccine and subsequently the effect of CD24-Fc, a CD24 and Fc fusion protein, on both the vaccine efficacy and induced irAEs in a mouse neuroblastoma model.MethodsTo test whether the whole tumor cell vaccination leads to autoimmune responses in other organ systems we harvested lung, heart, kidney and colon from naïve mice (n=3), unvaccinated tumor only mice (n=3),...
Journal of Burn Care & Research
Introduction Autologous skin cell suspensions (ASCS) are useful for treating burn wounds, includi... more Introduction Autologous skin cell suspensions (ASCS) are useful for treating burn wounds, including in adjunct with split thickness skin grafts (STSG) for full thickness injuries. Careful wound care is crucial after ASCS application to prevent leakage out of the wound bed. Solution blow spinning (SBS) can be used to spray polymer fiber mats with varied flexibility, adhesion, and absorption. Wounds treated with ASCS and SBS dressings demonstrate equivalent re-epithelialization as those treated conventionally. SBS polymers are currently applied using commercial airbrushes with limited control of sterility, pressure, and deposition rate, and have only been evaluated when applied after ASCS. This work investigates a novel SBS prototype designed to address these limitations and simultaneously spray cells and dressings. Methods A SBS prototype was engineered combining a 3D printed, biocompatible, disposable dual-chambered nozzle, a reusable handheld module with programmable motorized actu...
Figure S4. Effect of HIFU alone at 24, 48 and 72 hrs on circulating cytokines.
Figure S6. Effect of αCTLA-4 + αPD-L1 only at 24 and 48 hrs after last checkpoint inhibitor dos... more Figure S6. Effect of αCTLA-4 + αPD-L1 only at 24 and 48 hrs after last checkpoint inhibitor dose on IFN-Æ".
Figure S7. Immune memory effects in mice treated with HIFU+ αCTLA-4 + αPD-L1
This file includes supplementary methods and results.
Figure S5. Tumor growth curves of left and right limbs of mice with bilateral tumors.
Figure S1. Time-lapse of tumor growth in untreated mice and mice treated with HIFU+ αCTLA-4 + α... more Figure S1. Time-lapse of tumor growth in untreated mice and mice treated with HIFU+ αCTLA-4 + αPD-L1, HIFU alone, and αCTLA-4 + αPD-L1.
Figure S3. Circulating cellular profile in contralateral lymph nodes after treating mice with HIF... more Figure S3. Circulating cellular profile in contralateral lymph nodes after treating mice with HIFU only.
Figure S2. Immune cell infiltration within neuroblastoma tumors pre- and at 24, 48, & 72-hrs post... more Figure S2. Immune cell infiltration within neuroblastoma tumors pre- and at 24, 48, & 72-hrs post-HIFU alone.
ACS Applied Materials & Interfaces
Pediatrics
Introduction Although parents have been the main target for child abuse prevention, other caregiv... more Introduction Although parents have been the main target for child abuse prevention, other caregivers are known to also be important contributors. The purpose of this study was to evaluate factors contributing to severe injury in non-accidental trauma and identify caregiver groups for child abuse injury education and prevention. Methods Records of children admitted to a children’s hospital between 2013 and 2015 for …
Bioengineering & Translational Medicine
Adhesions are dense, fibrous bridges that adjoin tissue surfaces due to uncontrolled inflammation... more Adhesions are dense, fibrous bridges that adjoin tissue surfaces due to uncontrolled inflammation following postoperative mesothelial injury. A widely used adhesion barrier material in Seprafilm often fails to prevent transverse scar tissue deposition because of its poor mechanical properties, rapid degradation profile, and difficulty in precise application. Solution blow spinning (SBS), a polymer fiber deposition technique, allows for the placement of in situ tissue‐conforming and tissue‐adherent scaffolds with exceptional mechanical properties. While biodegradable polymers such as poly(lactic‐co‐glycolic acid) (PLGA) have desirable strength, they exhibit bulk biodegradation rates and inflammatory profiles that limit their use as adhesion barriers and result in poor tissue adhesion. Here, viscoelastic poly(lactide‐co‐caprolactone) (PLCL) is used for its pertinent biodegradation mechanism. Because it degrades via surface erosion, spray deposited PLCL fibers can dissolve new connecti...
Burns, 2022
Autologous skin cell suspensions (ASCS) can treat burns of varying depths with the advantage of r... more Autologous skin cell suspensions (ASCS) can treat burns of varying depths with the advantage of reduced donor site wound burden. The current standard primary dressing for ASCS is a nonabsorbant, non-adherent, perforated film (control) which has limited conformability over heterogeneous wound beds and allows for run-off of the ASCS. To address these concerns, a novel spray-on polymer formulation was tested as a potential primary dressing in porcine deep partial thickness (DPT) and full thickness (FT) wounds. It was hypothesized that the polymer would perform as well as control dressing when evaluating wound healing and scarring. DPT or FT wounds were treated with either a spray-on poly(lactic-co-glycolic acid) (PLGA) and poly(lactide-co-caprolactone) (PLCL) formulation or control ASCS dressings. Throughout the experimental time course (to day 50), we found no significant differences between polymer and control wounds in % re-epithelialization, graft-loss, epidermal or dermal thickness, or % dermal cellularity in either model. Pigmentation, erythema, elasticity, and trans-epidermal water loss (TEWL), were not significantly altered between the treatment groups, but differences between healing wounds/scars and un-injured skin were observed. No cytotoxic effect was observed in ASCS incubated with the PLGA and PLCL polymers. These data suggest that the novel spray-on polymer is a viable option as a primary dressing, with improved ease of application and conformation to irregular wounds. Polymer formulation and application technique should be a subject of future research.
The American Journal of Surgery, 2021
INTRODUCTION Non-accidental trauma (NAT) affects 2 per 100,000 children annually in the US and ma... more INTRODUCTION Non-accidental trauma (NAT) affects 2 per 100,000 children annually in the US and may go unrecognized. The aim of this study to quantify the burden of NAT and to evaluate regional variations in mortality. METHODS The Kids Inpatient Database (2000-2012) was queried for pediatric patients presenting with a diagnosis of NAT. Data was obtained on demographic, clinical and hospital-level characteristics. Primary outcome measure was mortality. Multivariable logistic regression models for age, sex, race/ethnicity, insurance status, income quartile, hospital volume, region (Northeast, South, West and Midwest), teaching status, and injury severity scores. RESULTS NAT represented 1.92% (n = 15,999) of all trauma patients. Mortality rates were 3.98% for patients presenting with NAT. African American children had a higher likelihood of mortality compared to White children (OR[95%CI]:1.35[1.03-1.79]), however, this effect was not statistically significant for patients being treated at designated children's hospitals (OR[95%CI]:1.23(0.78-1.95) and urban facilities (OR[95%CI]:1.30[0.99-1.72]). Statistically significant regional variations in mortality, lost significance for patients treated at designated children's hospitals (p > 0.05). CONCLUSION NAT has devastating consequences and is associated with a high mortality rate. Treatment at designated children's hospitals results in the loss of variation in mortality, resulting in diminished disparities and improved outcomes. These findings align with current trends towards the "regionalization of pediatric health care" and reflects the value of regional transfer centers that are.
ACS Biomaterials Science & Engineering, 2021
Pressure-sensitive adhesives typically used for bandages are nonbiodegradable, inhibiting healing... more Pressure-sensitive adhesives typically used for bandages are nonbiodegradable, inhibiting healing, and may cause an allergic reaction. Here, we investigated the effect of biodegradable copolymers with promising thermomechanical properties on wound healing for their eventual use as biodegradable, biocompatible adhesives. Blends of low molecular weight (LMW) and high molecular weight (HMW) poly(lactide-co-caprolactone) (PLCL) are investigated as tissue adhesives in comparison to a clinical control. Wounds treated with PLCL blend adhesives heal completely with similar vascularization, scarring, and inflammation indicators, yet require fewer dressing changes due to integration of the PLCL adhesive into the wound. A blend of LMW and HMW PLCL produces an adhesive material with significantly higher adhesive strength than either neat polymer. Wound adhesion is comparable to a polyurethane bandage, utilizing conventional nonbiodegradable adhesives designed for extremely strong adhesion.
Journal of the American College of Surgeons, 2020
Journal of the American College of Surgeons, 2020
Figure. Prophylactic, low-dose heparin administration decreases pulmonary growth and function. Co... more Figure. Prophylactic, low-dose heparin administration decreases pulmonary growth and function. Compared to controls, high-dose heparin administration led to therapeutic anticoagulation levels, shown as anti-factor Xa level, while low-dose heparin did not (A). Low-dose heparin significantly decreased lung volume and inspiratory capacity (B). Similarly, low-dose heparin decreased septal surface area, alveolar volume, and capillary volume, but increased mean septal thickness (C). Representative H&E stained lung tissue from control and low-dose heparin groups (D). CONCLUSIONS: Prophylactic, low-dose heparin administration significantly impaired pulmonary growth and development. This finding is of particular concern, as only a minority of neonates will receive therapeutic levels of heparin anticoagulation, but many will receive nontherapeutic doses for a variety of reasons. Therefore, heparin administration in neonates with congenital diaphragmatic hernia-associated pulmonary hypoplasia or other hypoplastic lung disease might need to be reconsidered.
Uploads
Papers by Anthony Sandler