The Secretome of Hypoxia Conditioned hMSC Loaded in a Central Depot Induces Chemotaxis and Angiogenesis in a Biomimetic Mineralized Collagen Bone Replacement Material

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Abstract

The development of biomaterials with intrinsic potential to stimulate endogenous tissue regeneration at the site of injury is a main demand on future implants in regenerative medicine. For critical-sized bone defects, an in situ tissue engineering concept is devised based on biomimetic mineralized collagen scaffolds. These scaffolds are functionalized with a central depot loaded with a signaling factor cocktail, obtained from secretome of hypoxia-conditioned human mesenchymal stem cells (MSC). Therefore, hypoxia-conditioned medium (HCM)-production is standardized and adapted to achieve high signaling factor-yields; a concentration protocol based on dialysis and freeze-drying is established to enable the integration of sufficient and defined amounts into the depot. In humid milieu-as after implantation-signaling factors are released by forming a chemotactic gradient, inducing a directed migration of human bone marrow stroma cells (hBMSC) into the scaffold. Angiogenic potential, determined by coculturing human umbilical vein endothelial cells (HUVEC) with osteogenically induced hBMSC shows prevascular structures, which sprout throughout the interconnected pores in a HCM-concentration-dependent manner. Retarded release by alginate-based (1 vol%) depots, significantly improves sprouting-depth and morphology of tubular structures. With the intrinsic potential to supply attracted cells with oxygen and nutrients, this bioactive material system has great potential for clinical translation.

Details

OriginalspracheEnglisch
Seiten (von - bis)e1901426
FachzeitschriftAdvanced healthcare materials
Jahrgang9
Ausgabenummer2
PublikationsstatusVeröffentlicht - Jan. 2020
Peer-Review-StatusJa

Externe IDs

Scopus 85078181262
ORCID /0000-0001-9075-5121/work/142237808

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

  • Adult, Angiogenesis Inducing Agents/chemistry, Biomimetic Materials, Bone Regeneration/physiology, Bone Substitutes/chemistry, Calcification, Physiologic/drug effects, Cell Hypoxia, Cell Movement, Cells, Cultured, Collagen/chemistry, Culture Media, Conditioned/chemistry, Freeze Drying, Human Umbilical Vein Endothelial Cells, Humans, Male, Mesenchymal Stem Cells/cytology, Tissue Scaffolds/chemistry