Effect of scaffold architecture and BMP-2/BMP-7 delivery on in vitro bone regeneration

Abstract

The aim of this study was to develop 3-D tissue engineered constructs that mimic the in vivo conditions through a self-contained growth factor delivery system. A set of nanoparticles providing the release of BMP-2 initially followed by the release of BMP-7 were incorporated in poly(ε-caprolactone) scaffolds with different 3-D architectures produced by 3-D plotting and wet spinning. The release patterns were: each growth factor alone, simultaneous, and sequential. The orientation of the fibers did not have a significant effect on the kinetics of release of the model protein BSA; but affected proliferation of bone marrow mesenchymal stem cells. Cell proliferation on random scaffolds was significantly higher compared to the oriented ones. Delivery of BMP-2 alone suppressed MSC proliferation and increased the ALP activity to a higher level than that with BMP-7 delivery. Proliferation rate was suppressed the most by the sequential delivery of the two growth factors from the random scaffold on which the ALP activity was the highest. Results indicated the distinct effect of scaffold architecture and the mode of growth factor delivery on the proliferation and osteogenic differentiation of MSCs, enabling us to design multifunctional scaffolds capable of controlling bone healing.

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

“…Several controlled release systems promoting the delivery of GFs are combined in strategies with cells, with the goal of acting in a synergistic manner and promoting the enhancement of new tissue formation. Co-encapsulation of GFs and cells in hydrogels [2][3][4][5][6][7][8][9][10] and seeding of stem cells in microparticles or scaffolds loaded with bioactive agents [11][12][13][14][15][16][17][18] are among the most common TE strategies described in literature. Typically, GFs have been included in TE strategies through three main approaches: (1) incorporation within micro-and nano-particles, which can act as supplements for in vitro cell cultures or can be injected into the defect sites, stimulating in situ tissue healing.…”

Biomaterials Applicable for Alveolar Sockets Preservation: In Vivo and In Vitro Studies

“…Additional polymers used as BMP delivery systems include polyanhydrides, polypropylene fumurate, polyethylene glycol-PLA as well as polyphosphate (Lucas et al 1990;Miyamoto et al 1992;Renier and Kohn 1997;Behravesh et al 1999). Incorpoartion of BMP-2 and BMP-7 in polycaprolactone suppressed bone marrow mesenchymal stem cell proliferation and increased the alkaline phosphatase activity (osteogenic differentiation) (Yilgor et al 2010). An in vivo study determined the effects on osseointegration when polycaprolactone with BMP-2 coating was applied to bone screws.…”

Engineering Musculoskeletal Tissue Interfaces

“…Tissue engineering aims to mimic the structure, function and composition of the native tissues in the best possible way. In order to achieve this goal, several approaches have been employed including scaffold-based and scaffold-free strategies for engineering of tissues including; bone, cartilage, tendon, ligaments, nervous tissue, and orthopedic interfaces (Freed et al, 1998;Moffat et al, 2009;Yilgor et al, 2010;Erisken et al, 2011;Chen et al, 2015). In these, either cells are directly injected to the damage site, or biomaterials are implanted without cellular content, or cells and biomaterials are combined for in vitro or in vivo applications.…”