3D Collagen Hydrogel Promotes In Vitro Langerhans Islets Vascularization through ad-MVFs Angiogenic Activity

Abstract

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.

Engineering Functional Vascularized Beige Adipose Tissue from Microvascular Fragments of Models of Healthy and Type II Diabetes Conditions

“…In the context of diabetes, impaired angiogenesis is a common feature and contributor to diabetes-related morbidities. 51 Investigations in diabetes research, utilizing MVF, have explored using MVF to encourage vascularization of pancreatic islets for type I diabetic (T1D) applications, 52 –54 and demonstrated a delayed and reduced angiogenic growth of T1D MVF. 55,56 Though it is reasonable to speculate that the vascularization capacity of type II diabetic MVF might also be altered, as it is in obesity, 36 T1D, 55,56 or aging, 57 that along with work looking into how utilizing a model of type II diabetes as the source of MVF might alter its capacity for tissue engineering applications, had not been previously investigated.…”

Recovery of Bioactive Compounds from Marine Organisms: Focus on the Future Perspectives for Pharmacological, Biomedical and Regenerative Medicine Applications of Marine Collagen

“…This pattern leads to the formation of three parallel polypeptide α-chains, forming a triple-helix structure, and giving rise to 28 types of collagens [ 39 , 40 ]. In addition to being the main structural element of the extracellular matrix of human tissues, type I collagen also has numerous intrinsic properties, such as biocompatibility for many biological applications, bioactivity, biodegradability, and the ability, in its native form, to generate hydrogels, by a simple pH change [ 41 , 42 , 43 , 44 , 45 , 46 ]. Due to these important characteristics, it receives great attention in the biomedical field, both as a functional ingredient in different formulations and as a component of several products, such as medical devices and pharmaceutical systems [ 46 , 47 , 48 , 49 ].…”

“…In addition to being the main structural element of the extracellular matrix of human tissues, type I collagen also has numerous intrinsic properties, such as biocompatibility for many biological applications, bioactivity, biodegradability, and the ability, in its native form, to generate hydrogels, by a simple pH change [ 41 , 42 , 43 , 44 , 45 , 46 ]. Due to these important characteristics, it receives great attention in the biomedical field, both as a functional ingredient in different formulations and as a component of several products, such as medical devices and pharmaceutical systems [ 46 , 47 , 48 , 49 ]. Although collagen appeared in the first phase of evolution in primitive animals such as jellyfish, corals and sea anemones, the mammalian (especially bovine and porcine) form is the main source used in the industrial and biomedical fields [ 50 , 51 , 52 ].…”

Recombinant collagen hydrogels induced by disulfide bonds

“…These materials have also been used as scaffold material, 4,5 cell culture matrix, 6 drug delivery carrier, 7,8 biosensors, and H 2 O 2 stimulus‐response 9,10 . In recent years, multilayer porous collagen and functional hydrogel composite scaffolds have been designed as drug vehicles for cancer therapy 11–16 …”

“…11 Moreover, collagen hydrogels have been explored in regenerating damaged corneal stroma in vivo and improving vascularization in islets. 15,16 However, natural collagen also has limitations, such as inconsistent purity and quality. It is an easy contamination source for various pathogens carried by animals.…”