Injectable Hybrid Hydrogels, with Cell-Responsive Degradation, for Tumor Resection

Biocompatible soft materials have recently found applications in interventional endoscopy to facilitate resection of mucosal tumors. When neoplastic lesions are in organs that can be easily damaged by perforation, such as stomach, intestine, and esophagus, the formation of a submucosal fluid cushion (SFC) is needed to lift the tumor from the underlying muscle during the resection of neoplasias. Such procedure is called endoscopic submucosal dissection (ESD). We describe an injectable, biodegradable, hybrid hydrogel able to form a SFC and to facilitate ESD. The hydrogel, based on polyamidoamines, contains breakable silica nanocapsules covalently bound to its network and able to release biomolecules. To promote degradation, the hydrogel is composed of cleavable disulfide moieties that are reduced by the cells through secretion of glutathione. The same stimulus triggers the breaking of the silica nanocapsules; therefore, the entire hybrid material can be completely degraded and its decomposition depends entirely on the presence of cells. Interestingly, the hydrogel precursor solution showed rapid gelation when injected in vivo and afforded a long-lasting high mucosal elevation, keeping the cushion volume constant during the dissection. This novel material can provide a solution to ESD limitations and promote healing of tissues after surgery

Effects of laparoscopic sleeve gastrectomy on gastric structure and function documented by Magnetic Resonance Imaging are strongly associated with post-operative weight loss and quality of life: a prospective study

BACKGROUND: This prospective study applied magnetic resonance imaging (MRI) to assess the effect of laparoscopic sleeve gastrectomy (LSG) on gastric structure and function. The impact of these changes on patient outcomes was analyzed. METHOD: Obese patients without gastrointestinal symptoms referred for bariatric surgery were recruited prospectively. Pre-operative assessment included (i) high-resolution manometry and pH-impedance monitoring and (ii) magnetic resonance imaging (MRI) measurement of gastric capacity, accommodation, and emptying with the 400 ml liquid Nottingham test meal (NTM). Studies were repeated 6-7 months after LSG. Weight loss and changes in the Gastrointestinal Quality of Life Index (GIQLI) assessed patient outcomes. RESULTS: From 35 patients screened, 23 (66%) completed the study (17 females, age 36 ± 10 years, BMI 42 ± 5 kg/m2). Mean excess weight loss was 59 ± 18% at follow-up. Total gastric volume (capacity) after the meal was 467 mL (455-585 ml) before and 139 mL (121-185 ml) after LSG (normal reference 534 (419-675) mL), representing a mean 70% reduction (p < 0.0001). Similar findings were present for gastric content volume indicating rapid early-phase gastric emptying (GE) post-LSG. Conversely, late-phase GE was slower post-LSG (2.5 ± 1.0 vs. 1.4 ± 0.6 mL/min; p < 0.0001; (reference 1.5(1.4-4.9) mL/min)). Patients with ≥ 80% reduction in gastric capacity had greater weight loss (p = 0.008), but worse gastrointestinal outcomes (p = 0.023). CONCLUSIONS: MRI studies quantified the marked reduction in gastric capacity after LSG. The reduction in capacity was associated with rapid early- but slow late-phase GE after surgery. These changes were associated with weight loss; however, reductions in gastric capacity ≥ 80% were linked to increased acid reflux and impacted on gastrointestinal quality of life

The causes of gastroesophageal reflux after laparoscopic sleeve gastrectomy: quantitative assessment of the structure and function of the esophagogastric junction by magnetic resonance imaging and high-resolution manometry

BACKGROUND: The incidence of de novo gastroesophageal reflux disease (GERD) after LSG is substantial. However, an objective correlation with the structural gastric and EGJ changes has not been demonstrated yet. We aimed to prospectively evaluate the effects of laparoscopic sleeve gastrectomy (LSG) on the structure and function of the esophagogastric junction (EGJ) and stomach. METHODS: Investigations were performed before and after > 50% reduction in excess body weight (6-12 months after LSG). Subjects with GERD at baseline were excluded. Magnetic Resonance Imaging (MRI), high-resolution manometry (HRM), and ambulatory pH-impedance measurements were used to assess the structure and function of the EGJ and stomach before and after LSG. RESULTS: From 35 patients screened, 23 (66%) completed the study (age 36 ± 10 years, BMI 42 ± 5 kg/m$^{2}$). Mean excess weight loss was 59 ± 18% after 7.1 ± 1.7-month follow-up. Esophageal acid exposure (2.4 (1.5-3.2) to 5.1 (2.8-7.3); p = 0.040 (normal  80% reduction in gastric capacity (TGV) had the highest prevalence of symptomatic GERD. CONCLUSION: LSG has multiple effects on the EGJ and stomach that facilitate reflux. In particular, EGJ disruption as indicated by increased (more obtuse) esophagogastric insertion angle and small gastric capacity were associated with the risk of GERD after LSG. clinicaltrials.gov: NCT01980420

Frozen Microemulsions for MAPLE Immobilization of Lipase

Candida rugosa lipase (CRL) was deposited by matrix assisted pulsed laser evaporation (MAPLE) in order to immobilize the enzyme with a preserved native conformation, which ensures its catalytic functionality. For this purpose, the composition of the MAPLE target was optimized by adding the oil phase pentane to a water solution of the amino acid 3-(3,4-dihydroxyphenyl)-2-methyl-l-alanine (m-DOPA), giving a target formed by a frozen water-lipase-pentane microemulsion. Fourier transform infrared (FTIR) spectroscopy and atomic force microscopy (AFM) were used to investigate the structure of MAPLE deposited lipase films. FTIR deconvolution of amide I band indicated a reduction of unfolding and aggregation, i.e., a better preserved lipase secondary structure in the sample deposited from the frozen microemulsion target. AFM images highlighted the absence of big aggregates on the surface of the sample. The functionality of the immobilized enzyme to promote transesterification was determined by thin layer chromatography, resulting in a modified specificity

Patient-specific stomach biomechanics before and after laparoscopic sleeve gastrectomy

Background: Obesity has become a global epidemic. Bariatric surgery is considered the most effective therapeutic weapon in terms of weight loss and improvement of quality of life and comorbidities. Laparoscopic sleeve gastrectomy (LSG) is one of the most performed procedures worldwide, although patients carry a nonnegligible risk of developing post-operative GERD and BE. Objectives: The aim of this work is the development of computational patient-specific models to analyze the changes induced by bariatric surgery, i.e., the volumetric gastric reduction, the mechanical response of the stomach during an inflation process, and the related elongation strain (ES) distribution at different intragastric pressures. Methods: Patient-specific pre- and post-surgical models were extracted from Magnetic Resonance Imaging (MRI) scans of patients with morbid obesity submitted to LSG. Twenty-three patients were analyzed, resulting in forty-six 3D-geometries and related computational analyses. Results: A significant difference between the mechanical behavior of pre- and post-surgical stomach subjected to the same internal gastric pressure was observed, that can be correlated to a change in the global stomach stiffness and a minor gastric wall tension, resulting in unusual activations of mechanoreceptors following food intake and satiety variation after LSG. Conclusions: Computational patient-specific models may contribute to improve the current knowledge about anatomical and physiological changes induced by LSG, aiming at reducing post-operative complications and improving quality of life in the long run

A biomechanical assessment of laparoscopic sleeve gastrectomy with a patient-specific approach

Obesity has become a global epidemic and bariatric surgery (BS) is one of the most commonly performed gastrointestinal operations thanks to the loss of a large amount of weight and an improvement of patients’ clinical situation. Among different BSs, laparoscopic sleeve gastrectomy (LSG) is currently the most performed procedure worldwide [1], but some limitations still remain and late complications may arise (e.g., GERD). For these reasons, the development of computational patient-specific models represents a valuable solution to overcome these limits and controversies [2]. Indeed, within this work, patient-specific pre- and post-surgical models were extracted from MRI scans of twenty-three patients who underwent LSG [3]. Forty-six computational analyses were realized, focusing on the volumetric gastric reduction after LSG, the mechanical response of the stomach during an inflation process and the elongation strain (LE) distribution at different intragastric pressures. Results were significant in assessing a different mechanical behaviour of pre- and post-surgical stomachs subjected to the same internal gastric pressure. This response can be correlated to unusual activations of mechanoreceptors and thus variation of satiety after LSG. All these insights aim at improving the current knowledge about BS, enhancing postsurgical success and quality of life in the long run. REFERENCES [1] H. Buchwald, D.M. Oien, Metabolic/bariatric surgery worldwide 2011, Obes. Surg. 23 427–436, 2013 https://doi.org/10.1007/s11695-012-0864-0. [2] I. Toniolo, C. Salmaso, G. Bruno, A. De Stefani, C. Stefanini, A.L.T. Gracco, E.L. Carniel, Anisotropic computational modelling of bony structures from CT data: An almost automatic procedure, Comput. Methods Programs Biomed. 189 1–11, 2020 https://doi.org/10.1016/j.cmpb.2020.105319. [3] G. Quero, C. Fiorillo, B. Dallemagne, P. Mascagni, J. Curcic, M. Fox, S. Perretta, The Causes of Gastroesophageal Reflux after Laparoscopic Sleeve Gastrectomy: Quantitative Assessment of the Structure and Function of the Esophagogastric Junction by Magnetic Resonance Imaging and High-Resolution Manometry, Obes. Surg. 30 2108–2117, 2020 https://doi.org/10.1007/s11695-020-04438-y

dabPna: Design, Synthesis, And Dna Binding Studies

In continuing our research efforts for developing new oligodeoxynucleotide (ODN)-like drugs and diagnostics, we designed diaminobutyric peptide nucleic acids (dabPNAs), nucleopeptides characterized by a diaminobutyric-based building block that is an isomer of the aminoethylglycyl PNA (aegPNA) unit and the acyclic modification of the aminoprolyl PNA (ampPNA) monomer. In this work we present the solid phase synthesis of a dabPNA oligomer and of two aegPNAs containing a single dabPNA unit. A study relative to their binding ability towards DNA is also reported even in comparison with the well known aegPNAs