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Highly porous collagen scaffolds for building 3D vascular networks: structure and property relationships

Organ transplantation success is hampered by the availability of donor organs and the risk of rejection due to immunological mismatch. Tissue engineering could address these problems by growing injured tissues in the lab using scaffolds with patient’s own cells.

Scaffolds provide the structural and mechanical framework for lab-grown tissues, mimicking closely the native 3D microenvironment. Some scaffolds are made of very porous biological materials, providing the appropriate support for cells to attach and grow.

Studying scaffold architecture

Designing proper conditions for lab-grown tissues can open new research directions that will ultimately lead to better tissue and organ repair. With the support of the Marie Curie programme, the 3DSTAR project investigated the influence of scaffold pore architecture through systematic in vitro experimentation and structure characterisation. ″Our aim was to determine the optimal spatial conditions required to grow bone and microvasculature in a dish,″ explains the Marie Skłodowska-Curie fellow Dr Sasha Berdichevski.

The researcher employed freeze drying to produce randomly aligned (isotropic) and unidirectionally aligned (anisotropic) scaffold configurations. She characterised the pore architecture using X-ray tomography and a code, developed on-site.

Comparative experiments testing scaffolds with different pore configurations helped determine how 3D pore geometry affects the way cells attach and grow, and how they start producing the engineered tissue. The generated scaffolds were evaluated for vascular organisation and bone formation using immunohistochemistry, confocal imaging and an array of molecular and biochemical assays.

Further emphasis was given to scaffold permeability as a function of pore architecture characteristics. According to Dr Berdichevski, “permeability is central in nutrient diffusion and waste removal but has been largely understudied.″

In vitro experiments with different cell types and culture conditions helped scientists understand how scaffold structure affects endothelial cell organisation into vascular-like structures, and osteoblast differentiation and mineralisation.

Experimental data demonstrated that anisotropic scaffolds are preferable for the formation of bone and micro-vessels. In addition, when blood vessel cells are co-cultured together with supporting cells, they promote better scaffold vascularisation.

The future of tissue engineering

The 3DSTAR study provides a better understanding of the appropriate conditions for the in vitro formation of bone tissue and capillary networks, potentially helping to design the right microenvironment to grow vascularised organs and whole bone. Future plans include the investigation of empty and cell-seeded anisotropic scaffolds in bone formation in vivo. Analysis of the host immune response against vascularised or bone scaffolds in both 3D configurations should be performed before proceeding further with their in vivo use.

Overall, tissue engineering holds great promise for organ regeneration, eliminating the need for donor organs and preventing organ rejection. Apart from improving the quality of life of many people, engineered tissues enable scientific and technological advances in academic research and the pharmaceutical industry as platforms for drug testing or alternatives to current human disease models. In view of the future, Dr Berdichevski hopes for a “successful translation of the scaffold research into the clinic, contributing to saving patients’ lives.″

Reference source : Highly porous collagen scaffolds for building 3D vascular networks: structure and property relationships

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