Encapsulation of Mesenchymal Stem Cells Improves Vascularization of Alginate-Based Scaffolds

Abstract

Vascularization of bioartificial tissues can be significantly enhanced by the generation of an arteriovenous (AV) loop. Besides the surgical vascularization, the choice of the scaffold and the applied cells are indispensable cofactors. The combination of alginate dialdehyde and gelatin (ADA-GEL) and mesenchymal stem cells (MSCs) is a promising approach with regard to biocompatibility, biodegradation, as well as de novo tissue formation. In this study, we targeted the investigation of the vascularization of ADA-GEL with and in the absence of encapsulated MSCs in the AV loop model. A Teflon chamber filled with ADA-GEL microcapsules was placed in the groin of Lewis rats and an AV loop was placed into the chamber. Group A encompassed the ADA-GEL without MSCs, whereas group B contained 2 × 10 DiI-labeled MSCs/mL ADA-GEL. Four weeks postoperatively, tissue formation and vascularization were investigated by histology and microcomputed tomography. We were able to prove vascularization originating from the AV loop in both groups with statistically significant more vessels in group B containing MSCs. Moreover, encapsulated MSCs promoted biodegradation of the ADA-GEL microcapsules. In the present study, we were able to demonstrate for the first time, the successful vascularization of ADA-GEL microcapsules by means of the AV loop. Furthermore, ADA-GEL displayed a good biocompatibility and encapsulation of MSCs into ADA-GEL microcapsule-enhanced vascularization as well as biodegradation.

Encapsulation of Rat Bone Marrow Derived Mesenchymal Stem Cells in Alginate Dialdehyde/Gelatin Microbeads with and without Nanoscaled Bioactive Glass for In Vivo Bone Tissue Engineering

“…Different degrees of degradation proceeding from the muscle to deeper layers could also be the cause of higher cell survival in areas far from the muscle after 4 weeks, compared to areas adjacent to muscular tissue, possibly leading to a decrease in RGD-motifs and thus important ECM components in areas with fast gelatin degradation. In a recent study from our group, similar results were obtained in a vascularization model using a central vascular axis in a custom-made Teflon chamber [ 39 ]. In this study, encapsulated rMSCs showed higher cell survival in peripheral areas compared to areas adjacent to the vascular axis.…”

Oxygen and nutrient delivery in tissue engineering: Approaches to graft vascularization

“…Furthermore, a period of increased angiogenesis was observed, which occurred after the peak of hypoxia between 7 and 10 days post‐implantation, supporting a potential local increase of angiogenic factors (Lokmic, Stillaert, Morrison, Thompson, & Mitchell, ). This angiogenic response can additionally be enhanced by encapsulation of MSCs (Steiner et al, ). Moreover, adaptations of the AV loop technique, for example, vascularized chambers that use the encapsulation of an artery and vein instead of using a vein graft‐based AV loop, have also been developed and have been reviewed recently (Yap, Yeoh, Morrison, & Mitchell, ).…”

The Use of Alginate Hydrogels for the Culture of Mesenchymal Stem Cells (MSCs): In Vitro and In Vivo Paradigms

“…Additionally, Paul et al successfully treated critical size calvarial defects with serum-loaded oxidized alginate-gelatin-biphasic calcium phosphate hydrogels with rat BM MSCs [74]. Importantly, encapsulation of MSCs in oxidized and natural alginate hydrogels increases vascularization which is of utmost importance in bone tissue engineering and the repair of vascular lesions [75] such as hind limb ischemia [76].…”