An Alginate-Based Hydrogel with a High Angiogenic Capacity and a High Osteogenic Potential

Abstract

In bone tissue engineering, autologous cells are combined with osteoconductive scaffolds and implanted into bone defects. The major challenge is the lack of post-implantation vascular growth into biomaterial. The objective of the present study was to develop a new alginate-based hydrogel that enhances the regeneration of bone defects after surgery. The viability of human bone marrow-derived mesenchymal stem cells (BM-MSCs) or human endothelial cells (ECs) cultured alone or together on the hydrogel was analyzed for 24 and 96 h. After seeding, the cells self-assembled and aggregated to form clusters. For functional validation, empty or cellularized hydrogel matrices were implanted ectopically at subcutaneous sites in nude mice. After 2 months, the matrices were explanted. Transplanted human cells were present, and we observed vessels expressing human von Willebrand factor (resulting from the incorporation of transplanted ECs into neovessels and/or the differentiation of BM-MSCs into ECs). The addition of BM-MSCs improved host vascularization and neovessel formation from human cells, relative to ECs alone. Although we did not observe bone formation, the transplanted BM-MSCs were able to differentiate into osteoblasts. This new biomaterial provided an appropriate three-dimensional environment for transplanted cells and has a high angiogenic capacity and an osteogenic potential.

Indirect co-culture of osteoblasts and endothelial cells in vitro based on a biomimetic 3D composite hydrogel scaffold to promote the proliferation and differentiation of osteoblasts

“…These microspheres exhibited favorable characteristics for the sustained release of VEGF. Previous studies have suggested that spherical aggregate networks with diameters between 100–400 μm are optimal for oxygen diffusion and species exchange [ 20 ]. Therefore, by optimizing the preparation conditions, we selected 350 μm calcium alginate microspheres with high uniformity for cell encapsulation in this experiment.…”

“…Among the various materials used for microsphere preparation, natural polysaccharide sodium alginate has gained significant attention owing to its high porosity, permeability, minimal mass transfer limitation, and high water content, particularly in loading and targeting drug delivery [ 18 , 19 ]. Alginate-based microcapsules have been extensively utilized for cell encapsulation, culture, and expansion of various cell types such as neural cells, osteoblasts, chondrocytes, and myoblasts [ 20 , 21 ]. This can be attributed to the rich biocompatibility and facile cross-linking process of alginates.…”

Strategies to Overcome the Barrier of Ischemic Microenvironment in Cell Therapy of Cardiovascular Disease

“…Interestingly, encapsulation techniques enable application, especially in chronic cardiovascular disease due to the delayed release of reparative and pro-angiogenic cells. Despite auspicious results, encapsulation as a strategy for cell therapy has mostly remained a preclinical concept thus far [ 40 , 41 , 42 , 43 , 44 ].…”

Identification and Characterization of a New Cold-Adapted and Alkaline Alginate Lyase TsAly7A from Thalassomonas sp. LD5 Produces Alginate Oligosaccharides with High Degree of Polymerization

“…These characteristics lead to the difference of their high-order structures, so polyM, polyG and their derivatives display different activities [ 3 ]. In medical fields, alginates with different arrangement and degree of polymerization (DP) have wide application prospects, including drug delivery and tissue engineering [ 4 , 5 , 6 ]. Alginate oligosaccharides (AOS) and their derivatives with different DPs are becoming popular due to their favorable biological activity and water solubility [ 1 ].…”