Mimicking Molecular Pathways in the Design of Smart Hydrogels for the Design of Vascularized Engineered Tissues

Biomaterials are pivotal in supporting and guiding vascularization for therapeutic applications. To design effective, bioactive biomaterials, understanding the cellular and molecular processes involved in angiogenesis and vasculogenesis is crucial. Biomaterial platforms can replicate the interactions between cells, the ECM, and the signaling molecules that trigger blood vessel formation. Hydrogels, with their soft and hydrated properties resembling natural tissues, are widely utilized; particularly synthetic hydrogels, known for their bio-inertness and precise control over cell-material interactions, are utilized. Naturally derived and synthetic hydrogel bases are tailored with specific mechanical properties, controlled for biodegradation, and enhanced for cell adhesion, appropriate biochemical signaling, and architectural features that facilitate the assembly and tubulogenesis of vascular cells. This comprehensive review showcases the latest advancements in hydrogel materials and innovative design modifications aimed at effectively guiding and supporting vascularization processes. Furthermore, by leveraging this knowledge, researchers can advance biomaterial design, which will enable precise support and guidance of vascularization processes and ultimately enhance tissue functionality and therapeutic outcomes

3d collagen hydrogel promotes in vitro langerhans islets vascularization through ad-mvfs angiogenic activity

Adipose derived microvascular fragments (ad-MVFs) consist of effective vascularization units able to reassemble into efficient microvascular networks. Because of their content in stem cells and related angiogenic activity, ad-MVFs represent an interesting tool for applications in regenerative medicine. Here we show that gentle dissociation of rat adipose tissue provides a mixture of ad-MVFs with a length distribution ranging from 33–955 µm that are able to maintain their original morphology. The isolated units of ad-MVFs that resulted were able to activate transcriptional switching toward angiogenesis, forming tubes, branches, and entire capillary networks when cultured in 3D collagen type-I hydrogel. The proper involvement of metalloproteases (MMP2/MMP9) and serine proteases in basal lamina and extracellular matrix ECM degradation during the angiogenesis were concurrently assessed by the evaluation of alpha-smooth muscle actin (αSMA) expression. These results suggest that collagen type-I hydrogel provides an adequate 3D environment supporting the activation of the vascularization process. As a proof of concept, we exploited 3D collagen hydrogel for the setting of ad-MVF–islet of Langerhans coculture to improve the islets vascularization. Our results suggest potential employment of the proposed in vitro system for regenerative medicine applications, such as the improving of the islet of Langerhans engraftment before transplantation

Validation of an electrogoniometry system as a measure of knee kinematics during activities of daily living

Purpose: The increasing use of electrogoniometry (ELG) in clinical research requires the validation of different instrumentation. The purpose of this investigation was to examine the concurrent validity of an ELG system during activities of daily living. Methods: Ten asymptomatic participants gave informed consent to participate. A Biometrics SG150 electrogoniometer was directly compared to a 12 camera three dimensional motion analysis system during walking, stair ascent, stair descent, sit to stand, and stand to sit activities for the measurement of the right knee angle. Analysis of validity was undertaken by linear regression. Standard error of estimate (SEE), standardised SEE (SSEE), and Pearson’s correlation coefficient r were computed for paired trials between systems for each functional activity. Results: The 95% confidence interval of SEE was reasonable between systems across walking (LCI = 2.43 °; UCI = 2.91 °), stair ascent (LCI = 2.09 °; UCI = 2.42 °), stair descent (LCI = 1.79 °; UCI = 2.10 °), sit to stand (LCI = 1.22 °; UCI = 1.41 °), and stand to sit (LCI = 1.17 °; UCI = 1.34 °). Pearson’s correlation coefficient r across walking (LCI = 0.983; UCI = 0.990), stair ascent (LCI = 0.995; UCI = 0.997), stair descent (LCI = 0.995; UCI = 0.997), sit to stand (LCI = 0.998; UCI = 0.999), and stand to sit (LCI = 0.996; UCI = 0.997) was indicative of a strong linear relationship between systems. Conclusion: ELG is a valid method of measuring the knee angle during activities representative of daily living. The range is within that suggested to be acceptable for the clinical evaluation of patients with musculoskeletal conditions

Neural Crest-Derived Chondrocytes Isolation for Tissue Engineering in Regenerative Medicine

Chondrocyte transplantation has been successfully tested and proposed as a clinical procedure aiming to repair articular cartilage defects. However, the isolation of chondrocytes and the optimization of the enzymatic digestion process, as well as their successful in vitro expansion, remain the main challenges in cartilage tissue engineering. In order to address these issues, we investigated the performance of recombinant collagenases in tissue dissociation assays with the aim of isolating chondrocytes from bovine nasal cartilage in order to establish the optimal enzyme blend to ensure the best outcomes of the overall procedure. We show, for the first time, that collagenase H activity alone is required for effective cartilage digestion, resulting in an improvement in the yield of viable cells. The extracted chondrocytes proved able to grow and activate differentiation/dedifferentiation programs, as assessed by morphological and gene expression analyses

Prognostic indicators of successful endoscopic sclerotherapy for prevention of rebleeding from oesophageal varices in cirrhosis: a long-term cohort study.

BACKGROUND: Although band ligation is now recommended for prevention of rebleeding from oesophageal varices in cirrhosis, sclerotherapy is still widely used. Patients submitted to chronic sclerotherapy undergo several endoscopies and experience a large number of serious complications. However, long-term outcome is poorly defined. AIMS: To assess the clinical course and prognostic indicators of patients undergoing chronic sclerotherapy for prevention of variceal rebleeding as a basis for future evaluation of long-term band ligation outcome. METHODS: Prospective cohort study; prognostic analysis by the Cox proportional hazards model. RESULTS: A total of 218 consecutive cirrhotic patients (37 Child class A, 154 B, 27 C) were enrolled in the study Varices were obliterated in 139 (64%) patients in a mean of 5 (+/-2.6) sessions and recurred in 58/139 (41.7%) within one year. A total of 132 (60%) patients experienced 283 rebleeding episodes and 73 (33%) died. Bleeding from oesophageal ulcers was the most serious complication causing 14% of all rebleeding episodes. Significant prognostic indicators of sclerotherapy outcome were: Child-Pugh class for variceal obliteration; gastric varices and platelet count for recurrence of varices; failure to obliterate varices, variceal size and gastric varices for rebleeding; blood urea nitrogen and failure to obliterate varices for death. Presence of gastric varices was the only prognostic indicator for death in the 79 patients not achieving variceal obliteration. A mean of 10 endoscopies and of 6 hospital admissions were needed per each patient with an estimated cost of US dollars 7154 per patient during the first two years of therapy. CONCLUSIONS: Sclerotherapy is a very demanding and costly treatment, and is associated with frequent and serious side-effects. The probability of treatment failure is significantly higher in Child C patients with gastric varices. Alternative treatments should be considered for these patients

Radiological evaluation of a case of chronic intestinal pseudo-obstruction (CIPO)

Chronic intestinal pseudo-obstruction (CIPO) is a severe form of gastrointestinal dysmotility (often due to derangement of the innervation and/or smooth muscle and/or interstitial cells of Cajal) with recurrent episodes of intestinal sub-occlusion. We describe a clinical setting and radiological features of CIPO in an 11-year-old girl with periodic relapses. Our attention was focused firstly on surgical causes, leading to a delay in the diagnosis; thus, is important detecting equivocal symptoms and considering the possible correlation to the CIPO for an early diagnosis and related prevention of acute episodes improving prognosis and quality of life of pediatric patients

The non-surgical management for hemorrhoidal disease. A systematic review

The non-surgical treatments for hemorrhoids are cost and time-saving techniques usually performed in patients suffering early hemorrhoidal disease. The most used are rubber band ligation (RBL), injection sclerotherapy (IS), and infrared coagulation (IRC). We performed a systematic review in order to evaluate: do these procedures really help to avoid further more aggressive treatments? What are the common harms? What are the rare harms? How many recurrences there are? A total of 21 RCTs were included in this review: 12 on RBL, 4 on IRC and 5 on IS. In RBL bleeding stops in up to 90% and III degree hemorrhoids improves in 78%-83.8%. IV degree prolapse should have a more invasive treatment. The commonest complications are bleeding and pain (8-80%). IRC related improvement is 78%, 51% and 22% for I, II and III degree. Post-operative pain occurs in 15- 100% and post-operative bleeding ranges from 15% to 44%. Recurrence rate is 13% at a three months follow-up. IS brings to the resolution of prolapse in 90%-100% of II degree and allows good results for III degree even if reported only by case series. The post-procedural pain is 36%-49%. Bleeding is a very rare harm. Even if not definitive, these treatments could be an alternative for mild symptomatic patients after a clear explanation of recurrence rates and possible complications