IADR Abstract Archives
An Injectable Self-Setting Calcium Phosphate-Alginate-iPS-MSCs Paste for Bone Tissue Engineering
Objectives: Induced pluripotent stem cell-derived mesenchymal stem cells (iPS-MSCs) are a promising source of readily accessible stem cells for obtaining large populations of stem cells for regenerative medicine. Cell delivery vehicle is the principal determinant for the success of cell-mediated tissue regeneration. Objectives: (1) develop a novel cell delivery system based on cell encapsulation in alginate microbeads and investigate iPS-MSC viability, proliferation and osteogenic differentiation in alginate microbeads; and (2) develop a novel tissue engineered construct by dispersing iPS-MSC loaded microbeads in calcium phosphate cement (CPC) paste and investigate in vivo bone regeneration efficiency.
Methods: IPS-MSCs (1×106/ml) were encapsulated in fast-degradable oxidized-alginate-fibrin microbeads (diameters of 100-500µm) via a microbead generator. Cell-loaded or cell-free microbeads were incorporated into CPC at 50% by volume of the construct. Degradable suture fibers were cut into 3mm filaments and added into CPC at 10% by volume for mechanical reinforcement. The mixed CPC paste was then filled into double cranial bone defects in nude rats.
Results: Cells maintained good viability inside microbeads after encapsulation and after injection from a syringe with a tip opening of 2.7mm. IPS-MSCs were able to be released from the degradable microbeads and demonstrated excellent proliferative potential (over 10-fold increase in live cell density from 1day to 14days), and up-regulations of osteogenic markers alkaline phosphatase (7.4-fold), collagen-I (4.3-fold), osteocalcin (1.8-fold), and Runx2 (2.1-fold) during 14-day osteogenic induction. More new bone grew into the defects in cell-loaded group than the cell-free control group at 3 months in vivo. The average new bone area fraction in cell-encapsulated group was (38.9±18.4)%, more than 2-fold the (15.6±11.2)% of control group (p<0.05).
Conclusions: The encapsulated iPS-MSCs can be released from the fast-degradable microbeads inside CPC and enhance bone regeneration. Fast-degradable microbeads in combination with CPC paste is a promising injectable material for cell delivery and bone regeneration.
Methods: IPS-MSCs (1×106/ml) were encapsulated in fast-degradable oxidized-alginate-fibrin microbeads (diameters of 100-500µm) via a microbead generator. Cell-loaded or cell-free microbeads were incorporated into CPC at 50% by volume of the construct. Degradable suture fibers were cut into 3mm filaments and added into CPC at 10% by volume for mechanical reinforcement. The mixed CPC paste was then filled into double cranial bone defects in nude rats.
Results: Cells maintained good viability inside microbeads after encapsulation and after injection from a syringe with a tip opening of 2.7mm. IPS-MSCs were able to be released from the degradable microbeads and demonstrated excellent proliferative potential (over 10-fold increase in live cell density from 1day to 14days), and up-regulations of osteogenic markers alkaline phosphatase (7.4-fold), collagen-I (4.3-fold), osteocalcin (1.8-fold), and Runx2 (2.1-fold) during 14-day osteogenic induction. More new bone grew into the defects in cell-loaded group than the cell-free control group at 3 months in vivo. The average new bone area fraction in cell-encapsulated group was (38.9±18.4)%, more than 2-fold the (15.6±11.2)% of control group (p<0.05).
Conclusions: The encapsulated iPS-MSCs can be released from the fast-degradable microbeads inside CPC and enhance bone regeneration. Fast-degradable microbeads in combination with CPC paste is a promising injectable material for cell delivery and bone regeneration.