‘Smart’ Microcarriers as Functional Component of Bioengineered Matrix With hMSC: A Case Study on hBMP2 Controlled Delivery For Bone Engineering
By fabrication an ordinate deposition of cells and biopolymer micro/nano carriers for the controlled bio-molecule delivery within a cross-linked hydrogels, a specific pattern can be designed obtaining an ordinate cell aggregate in a specific matrix that is able to stimulate the cells to differentiate into specific tissue structures during their cultivation in vitro. The advantage of this approach is the high potential level of control in cell and synthetic extracellular placement and alignment to create bioengineered microenvironment with a wide array of properties and geometries.
An example of this approach is described in this paper in the case of human-Mesechymal Stem Cells (hMSC) cultivated in to a 3D Ca-Alginate hydrogel (2% w/w) with Poly-Lactic Acid (PLA) microspheres (5 mg/cm3) for the controlled release of human-Bone Morphogenic Protein 2 (hBMP-2) at 20 ng/cm3/day in to a dynamic perfusion system. Osteogenic markers such as Alkaline Phosphatase (ALP) and osteocalcin (OC) have been observed after 7 and 21 days, respectively of cultivation together with an increase of the biomaterial stiffness due to calcium phosphate deposition within the matrix. The described hydrogel may be used as an injectable formulation during orthopedic surgery procedure bringing us closer to the ultimate goal of creating clinically relevant engineered tissues for human implantation and disease treatment..
Index Terms: Microcarriers, controlled delivery, stem cells, hydrogel, 3D scaffold, microenvironment, bone tissue engineering.