Corrigendum: Development and Characterization of a New Endoscopic Drug-Eluting Platform With Proven Efficacy in Acute and Chronic Experimental Colitis.

[This corrects the article DOI: 10.3389/fmed.2020.00415.].

Development and Characterization of a New Endoscopic Drug-Eluting Platform With Proven Efficacy in Acute and Chronic Experimental Colitis.

Background and Aims: Mucosal lesions refractory to biological treatments represent unmet needs in patients with inflammatory bowel disease (IBD) that require new treatment modalities. We developed and characterized a new endoscopic drug-eluting hydrogel (CoverGel) with proven efficacy in acute and chronic experimental colitis (EC) in rats. Methods: CoverGel was developed based on appropriate rheological, drug release, gelation, structural, and degradation property capacities to allow endoscopic application. Experimental colitis (EC) was induced by TNBS application in rats. In acute EC 40, rats were randomized in five groups (eight each): Sham, Control, CoverGel, CoverGel + Infliximab (IFX) and CoverGel + Vedolizumab (VDZ). In chronic EC, 12 rats were randomized in two groups (six each): IFX s.c. and CoverGel + IFX. Endoscopic, histological, and blood test were performed during follow-up to evaluate clinical success. Antibodies to IFX (ATIs) were evaluated in chronic EC animal study. Results: CoverGel is a biocompatible and bioadhesive reverse thermosensitive gelation hydrogel with a macroporous structure and drug release capacity. In acute EC animals treated with CoverGel + IFX or CoverGel + VDZ showed significantly clinical success (weight recovery, mucosal restoration, and bacterial translocation) as compared with controls and animals without a bioactive drug. In a chronic EC animal study, clinical efficacy was comparable in both groups. Levels of ATIs were significantly lower in animals treated with CoverGel + IFX vs. IFX s.c. (0.90 ± 0.06 µg/mL-c vs. 1.97 ± 0.66 µg/mL-c, p = 0.0025). Conclusions: CoverGel is an endoscopic vehicle to locally deliver biological drugs with proven efficacy in acute and chronic EC in rats and induce less immunogenicity reaction.

Comparative study of electrical and rheological properties of different solutions used in endoscopic mucosal resection.

BACKGROUND AND AIM: The study of electrical and rheological properties of solutions to carry out endoscopic resection procedures could determinate the best candidate. An ex vivo study with porcine stomachs was conducted to analyze electrical resistivity (R) and rheological properties (temperature, viscosity, height and lasting of the cushion) of different substances used in these techniques. METHODS: Tested solutions were: 0.9% saline (S), platelet-rich plasma (PRP), Gliceol (GC), hyaluronic acid 2% (HA), Pluronic-F127 20% (PL), saline with 10% glucose (GS), Gelaspan (GP), Covergel-BiBio (TB) and PRP with TB (PRP+TB). Measurements of electrical and rheological properties were done at 0, 15, 30, 45 and 60 min after submucosal injection. RESULTS: Solutions showed a wide variability of transepithelial R after submucosal injection. Substances able to maintain the highest R 60 min postinjection were TB (7 × 104 Ω), HA (7 × 104 Ω) and PL (7 × 104 Ω). Protective solutions against deep thermal injury (Tª lower than 60°C) were PL (47.6°C), TB (55°C) and HA (56.63°C). Shortest time to carry out resections were observed with GC (17.66″), PRP (20.3″) and GS (23.45″). Solutions with less cushion decrease (<25%) after 60 min were TB (11.74%), PL (18.63%) and PRP (22.12%). CONCLUSIONS: Covergel-BiBio, PL and HA were the best solutions with long-term protective effects (transepithelial R, lower thermal injury and less cushion decrease). Solutions with quicker resection time were GC, PRP and GS.

Submucosal injection of platelet-rich plasma in endoscopic resection of large sessile lesions.

AIM: To prospectively evaluate the efficacy of submucosal injection of platelet-rich plasma (PRP) on endoscopic resection of large sessile lesions. METHODS: Eleven patients were submitted to endoscopic mucosal resection (EMR) with prior injection of PRP, obtained at the time of endoscopy. Patients were followed during 1 mo. The incidence of adverse events (delayed bleeding or perforation) and the percentage of mucosal healing (MHR) after 4 wk were registered. RESULTS: EMR was performed in 11 lesions (46.4 mm ± 4 mm, range 40-70 mm). Delayed bleeding or perforation was not observed in any patient. Mean ulcerated area at baseline was 22.7 cm2 ± 11.7 cm2 whereas at week 4 were 2.9 cm2 ± 1.5 cm2. Patients treated with PRP showed a very high MHR after 4 wk (87.5%). CONCLUSION: PRP is an easy-to-obtain solution with proven and favourable biological activities that could be used in advanced endoscopic resection.

Endoscopic shielding technique, a new method in therapeutic endoscopy.

Prevention of late complications after large endoscopic resection is inefficient with current methods. Endoscopic shielding, as a simple and safe technique, has been proposed to improve the incidence of these events. Different methods, sheets or hydrogels, have showed proven efficacy in the prevention of late bleeding and perforation, as well as the improvement of tissue repair, in experimental models and in clinical practice.

Endoscopic shielding technique with a newly developed hydrogel to prevent thermal injury in two experimental models.

BACKGROUND AND AIM: A newly developed hydrogel, applied through the endoscope as an endoscopic shielding technique (EndoSTech), is aimed to prevent deep thermal injury and to accelerate the healing process of colonic induced ulcers after therapeutic endoscopy. METHODS: Lesions were performed in rats (n = 24) and pigs (n = 8). Rats were randomized to receive EndoSTech (eight rats each) with: saline (control), hyaluronic acid and product. In pigs, three ulcer sites were produced in each pig: endoscopic mucosal resection (EMR)-ulcer with prior saline injection (A; EMR-saline), EMR-saline plus EndoSTech with product (B; EMR-saline-P), and EMR with prior injection of product plus EndoSTech-P (C; EMR-P-P). At the end of the 14-day study, the same lesions were performed again in healthy mucosa to assess acute injury. Animals were sacrificed after 7 (rats) and 14 (pigs) days. Ulcers were macroscopically and histopathologically evaluated. Thermal injury (necrosis) was assessed with a 1-4 scale. RESULTS: In rats, treatment with product improved mucosal healing comparing with saline and hyaluronic acid (70% vs 30.3% and 47.2%; P = 0.003), avoiding mortality (0% vs 50% and 25%; P = 0.038), and perforation (0% vs 100% and 33.3%; P = 0.02); respectively. In pigs, submucosal injection of product induced a marked trend towards a less deep thermal injury (C = 2.25-0.46 vs A and B = 2.75-0.46; P = 0.127). Mucosal healing rate was higher with product (B = 90.2-3.9%, C = 91.3-5.5% vs A = 73.1-12.6%; P = 0.002). CONCLUSIONS: This new hydrogel demonstrates strong healing properties in preclinical models. In addition, submucosal injection of this product is able to avoid high thermal load of the gastrointestinal wall.

Efficacy of platelet-rich plasma as a shielding technique after endoscopic mucosal resection in rat and porcine models.

BACKGROUND AND STUDY AIMS: The aims were to assess the efficacy of endoscopic application of Platelet-rich plasma (PRP) to prevent delayed perforation and to induce mucosal healing after endoscopic resections. PATIENTS AND METHODS: Colonic induced lesions were performed in rats (n = 16) and pigs (n = 4). Animals were randomized to receive onto the lesions saline (control) or PRP. Animals underwent endoscopic follow-up. Thermal injury was assessed with a 1 - 4 scale: (1) mucosal necrosis; (2) submucosal necrosis; (3) muscularis propria necrosis; and (4) serosal necrosis RESULTS: Saline treatment showed 50 % of mortality in rats (P = 0.02). Mean ulcerated area after 48 hours and 7 days was significantly smaller with PRP than with saline (0.27 ±â€Š0.02 cm(2) and 0.08 ±â€Š0.01 cm(2) vs. 0.56 ±â€Š0.1 cm(2) and 0.40 ±â€Š0.06 cm(2); P < 0.001). The incidence of thermal injury was significantly lower with PRP (1.25 ±â€Š0.46) than in controls (2.25 ±â€Š0.50); P = 0.006. The porcine model showed a trend toward higher mucosal restoration in animals treated with PRP than with saline at weeks 1 and 2 (Median area in cm(2): 0.55 and 0.40 vs. 1.32 and 0.79) CONCLUSIONS: Application of PRP to colonic mucosal lesions showed strong healing properties in rat and porcine models.