Biodegradable, Tissue Adhesive Polyester Blends for Safe, Complete Wound Healing.

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.

Evaluating disparities in delivery of neoadjuvant guideline-based chemoradiation for rectal cancer: A multicenter, propensity score-weighted cohort study.

BACKGROUND: Despite guideline recommendations, some patients still receive care inappropriate for their clinical stage of disease. Identification of factors that contribute to variation in guideline base care may help eradicate disparities in the treatment of early and locally advanced rectal cancer. METHODS: The American College of Surgeons National Cancer Database from 2010 to 2015 was analyzed with propensity score weighting to identify factors associated with delivery and omission of neoadjuvant guideline-based chemoradiation (GBC) for those with early and locally advanced rectal cancer. RESULTS: Only 74% of patients with rectal cancer received stage-appropriate neoadjuvant chemoradiation; 4544 (88%) of those with early stage disease and 8675 (68%) in locally advanced disease. Chemotherapy and radiotherapy were not planned in 27% and 34% respectively, of those who did not receive GBC. Factors associated with receipt of non-guideline-based neoadjuvant chemoradiation were age >65 years, Medicare insurance, treatment at a community facility, West-South-Central geography, having locally advanced disease, and Charlson-Deyo score >3. Receipt of ideal guideline-based neoadjuvant chemoradiation conferred a survival benefit at 5 years. CONCLUSION: Patient and non-patient factors contribute to disparities in guideline-based delivery of neoadjuvant chemoradiation in the treatment of rectal cancer. Identification of these risk factors are important to help standardize care and improve survival outcomes.

Preclinical evaluation of ultrasound-augmented needle navigation for laparoscopic liver ablation.

PURPOSE: For laparoscopic ablation to be successful, accurate placement of the needle to the tumor is essential. Laparoscopic ultrasound is an essential tool to guide needle placement, but the ultrasound image is generally presented separately from the laparoscopic image. We aim to evaluate an augmented reality (AR) system which combines laparoscopic ultrasound image, laparoscope video, and the needle trajectory in a unified view. METHODS: We created a tissue phantom made of gelatin. Artificial tumors represented by plastic spheres were secured in the gelatin at various depths. The top point of the sphere surface was our target, and its 3D coordinates were known. The participants were invited to perform needle placement with and without AR guidance. Once the participant reported that the needle tip had reached the target, the needle tip location was recorded and compared to the ground truth location of the target, and the difference was the target localization error (TLE). The time of the needle placement was also recorded. We further tested the technical feasibility of the AR system in vivo on a 40-kg swine. RESULTS: The AR guidance system was evaluated by two experienced surgeons and two surgical fellows. The users performed needle placement on a total of 26 targets, 13 with AR and 13 without (i.e., the conventional approach). The average TLE for the conventional and the AR approaches was 14.9 mm and 11.1 mm, respectively. The average needle placement time needed for the conventional and AR approaches was 59.4 s and 22.9 s, respectively. For the animal study, ultrasound image and needle trajectory were successfully fused with the laparoscopic video in real time and presented on a single screen for the surgeons. CONCLUSION: By providing projected needle trajectory, we believe our AR system can assist the surgeon with more efficient and precise needle placement.

Are Current Technical Exclusion Criteria for Clinical Trials of Magnetic Resonance-Guided High-Intensity Focused Ultrasound Too Restrictive?: Early Experiences at a Pediatric Hospital.

Certain technical criteria must be met to ensure the treatment safety of magnetic resonance-guided high-intensity focused ultrasound. We retrospectively reviewed how our enrollment criteria were applied from 2014 to 2017 in a clinical trial of magnetic resonance-guided high-intensity focused ultrasound ablation of recurrent malignant and locally aggressive benign solid tumors. Among the 36 screened patients between 2014 and 2017, more than one-third were excluded for technical exclusion criteria such as the anatomic location and proximity to prosthetics. Overall, patients were difficult to accrue for this trial, given the incidence of these tumors. To increase potential accrual, screening exclusion criteria could be more generalized and centered on the ability to achieve an acceptable treatment safety margin, rather than specifically excluding on the basis of general anatomic areas.

Pressure-Sensitive Tissue Adhesion and Biodegradation of Viscoelastic Polymer Blends.

Viscoelastic blends of biodegradable polyesters with low and high molecular weight distributions have remarkably strong adhesion (significantly greater than 1 N/cm2) to soft, wet tissue. Those that transition from viscous flow to elastic, solidlike behavior at approximately 1 Hz demonstrate pressure-sensitivity yet also have sufficient elasticity for durable bonding to soft, wet tissue. The pressure-sensitive tissue adhesive (PSTA) blends produce increasingly stronger pull-apart adhesion in response to compressive pressure application, from 10 to 300 s. By incorporating a stiffer high molecular weight component, the PSTA exhibits dramatically improved burst pressure (greater than 100 kPa) when used as a tissue sealant. The PSTA's biodegradation mechanism can be switched from erosion (occurring primarily over the first 10 days) to bulk chemical degradation (and minimal erosion) depending on the chemistry of the high molecular weight component. Interestingly, fibrosis toward the PSTA is reduced when fast-occurring erosion is the dominant biodegradation mechanism.

Sprayable and biodegradable, intrinsically adhesive wound dressing with antimicrobial properties.

Conventional wound dressings are difficult to apply to large total body surface area (TBSA) wounds, as they typically are prefabricated, require a layer of adhesive coating for fixation, and need frequent replacement for entrapped exudate. Large TBSA wounds as well as orthopedic trauma and low-resource surgery also have a high risk of infection. In this report, a sprayable and intrinsically adhesive wound dressing loaded with antimicrobial silver is investigated that provides personalized fabrication with minimal patient contact. The dressing is composed of adhesive and biodegradable poly(lactic-co-glycolic acid) and poly(ethylene glycol) (PLGA/PEG) blend fibers with or without silver salt (AgNO3). in vitro studies demonstrate that the PLGA/PEG/Ag dressing has antimicrobial properties and low cytotoxicity, with antimicrobial silver controllably released over 7-14 days. In a porcine partial-thickness wound model, the wounds treated with both antimicrobial and nonantimicrobial PLGA/PEG dressings heal at rates similar to those of the clinical, thin film polyurethane wound dressing, with similar scarring. However, PLGA/PEG adds a number of features beneficial for wound healing: greater exudate absorption, integration into the wound, a 25% reduction in dressing changes, and tissue regeneration with greater vascularization. There is also modest improvement in epidermis thickness compared to the control wound dressing.

Improving the adhesion, flexibility, and hemostatic efficacy of a sprayable polymer blend surgical sealant by incorporating silica particles.

Commercially available surgical sealants for internal use either lack sufficient adhesion or produce cytotoxicity. This work describes a surgical sealant based on a polymer blend of poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) that increases wet tissue adherence by incorporation of nano-to-microscale silica particles, without significantly affecting cell viability, biodegradation rate, or local inflammation. In functional studies, PLGA/PEG/silica composite sealants produce intestinal burst pressures that are comparable to cyanoacrylate glue (160 mmHg), ∼2 times greater than the non-composite sealant (59 mmHg), and ∼3 times greater than fibrin glue (49 mmHg). The addition of silica to PLGA/PEG is compatible with a sprayable in situ deposition method called solution blow spinning and decreases coagulation time in vitro and in vivo. These improvements are biocompatible and cause minimal additional inflammation, demonstrating the potential of a simple composite design to increase adhesion to wet tissue through physical, noncovalent mechanisms and enable use in procedures requiring simultaneous occlusion and hemostasis. STATEMENT OF SIGNIFICANCE: Incorporating silica particles increases the tissue adhesion of a polymer blend surgical sealant. The particles enable interfacial physical bonding with tissue and enhance the flexibility of the bulk of the sealant, without significantly affecting cytotoxicity, inflammation, or biodegradation. These studies also demonstrate how silica particles decrease blood coagulation time. This surgical sealant improves upon conventional devices because it can be easily deposited with accuracy directly onto the surgical site as a solid polymer fiber mat. The deposition method, solution blow spinning, allows for high loading in the composite fibers, which are sprayed from a polymer blend solution containing suspended silica particles. These findings could easily be translated to other implantable or wearable devices due to the versatility of silica particles.

Laparoscopic Liver Resection with Augmented Reality: A Preclinical Experience.

INTRODUCTION: Intraoperative imaging, such as ultrasound, provides subsurface anatomical information not seen by standard laparoscopy. Currently, information from the two modalities may only be integrated in the surgeon's mind, an often distracting and inefficient task. The desire to improve intraoperative efficiency has guided the development of a novel, augmented reality (AR) laparoscopic system that integrates, in real time, laparoscopic ultrasound (LUS) images with the laparoscopic video. This study shows the initial application of this system for laparoscopic hepatic wedge resection in a porcine model. MATERIALS AND METHODS: The AR system consists of a standard laparoscopy setup, LUS scanner, electromagnetic tracking system, and a laptop computer for image fusion. Two liver lesions created in a 40-kg swine by radiofrequency ablation (RFA) were resected using the novel AR system and under standard laparoscopy. RESULTS: Anatomical details from the LUS were successfully fused with the laparoscopic video in real time and presented on a single screen for the surgeons. The RFA lesions created were 2.5 and 1 cm in diameter. The 2.5 cm lesion was resected under AR guidance, taking about 7 minutes until completion, while the 1 cm lesion required 3 minutes using standard laparoscopy and ultrasound. Resection margins of both lesions grossly showed noncoagulated liver parenchyma, indicating a negative-margin resection. CONCLUSIONS: The use of our AR system in laparoscopic hepatic wedge resection in a swine provided real-time integration of ultrasound image with standard laparoscopy. With more experience and testing, this system can be used for other laparoscopic procedures.

Retinal ganglion cell polarization using immobilized guidance cues on a tissue-engineered scaffold.

Cell transplantation therapies to treat diseases related to dysfunction of retinal ganglion cells (RGCs) are limited in part by an inability to navigate to the optic nerve head within the retina. During development, RGCs are guided by a series of neurotrophic factors and guidance cues; however, these factors and their receptors on the RGCs are developmentally regulated and often not expressed during adulthood. Netrin-1 is a guidance factor capable of guiding RGCs in culture and relevant to guiding RGC axons toward the optic nerve head in vivo. Here we immobilized Netrin-1 using UV-initiated crosslinking to form a gradient capable of guiding the axonal growth of RGCs on a radial electrospun scaffold. Netrin-gradient scaffolds promoted both the percentage of RGCs polarized with a single axon, and also the percentage of cells polarized toward the scaffold center, from 31% to 52%. Thus, an immobilized protein gradient on a radial electrospun scaffold increases RGC axon growth in a direction consistent with developmental optic nerve head guidance, and may prove beneficial for use in cell transplant therapies for the treatment of glaucoma and other optic neuropathies.