Bony Engineering Using Time-Release Porous Scaffolds to Provide Sustained Growth Factor Delivery

Abstract

Microporous scaffolds designed to improve bony repair have had limited success; therefore, we sought to evaluate whether time-released porous scaffolds with or without recombinant bone morphogenetic protein 2 (rhBMP-2) could enhance stem cell osteoinduction. Custom-made 15/85 hydroxyapatite/β-tricalcium phosphate scaffolds were left empty (E) or filled with rhBMP-2 (E+), calcium sulfate (CS), or CS and rhBMP-2 (CS+). All scaffolds were placed in media and weighed daily. Conditioned supernatant was analyzed for rhBMP-2 and then used to feed human adipose-derived mesenchymal stem cells (ASCs). Adipose-derived mesenchymal stem cell ALP activity, OSTERIX expression, and bone nodule formation were determined. E scaffolds retained 97% (SD, 2%) of the initial weight, whereas CS scaffolds had a near-linear 30% (SD, 3%) decrease over 60 days. E+ scaffolds released 155 (SD, 5) ng of rhBMP-2 (77%) by day 2. In contrast, CS+ scaffolds released only 30 (SD, 2) ng (10%) by day 2, and the remaining rhBMP-2 was released over 20 days. Conditioned media from E+ scaffolds stimulated the highest ALP activity and OSTERIX expression in ACSs on day 2. However, after day 6, media from CS+ scaffolds stimulated the highest ALP activity and OSTERIX expression in ASCs. Adipose-derived mesenchymal stem cells exposed to day 8 CS+-conditioned media produced significantly more bone nodules (10.1 [SD, 1.7] nodules per high-power field) than all other scaffolds. Interestingly, day 8 conditioned media from CS scaffolds simulated significantly more bone nodules than either E or E+ scaffold (P < 0.05 for both). Time-released hydroxyapatite/β-tricalcium phosphate porosity provides sustained growth factor release, enhances ASC osteoinduction, and may result in better in vivo bone formation.

Ticagrelor regulates osteoblast and osteoclast function and promotes bone formation in vivo via an adenosine‐dependent mechanism

“…Finally, the suspension was gelled by adding ∼150 mg/30 μl of ink of polyethylenimine (Sigma‐Aldrich, St. Louis, MO, USA) in a 10% wt/wt solution. Mixing and defoaming (1 min and 30 s, respectively) after the final addition completed the ink preparation procedure (31, 32).…”

Bone regeneration in critical bone defects using three‐dimensionally printed β‐tricalcium phosphate/hydroxyapatite scaffolds is enhanced by coating scaffolds with either dipyridamole or BMP‐2

“…Thus, we have developed hydroxyapatite (HA)/beta-tri-calcium phosphate (b-TCP) printable scaffold components that provide mechanical strength, conduct bone throughout the scaffold and remodel over time. 16,[19][20][21] Moreover, coating these porous scaffolds with osteoinductive agents such as BMP-2 can further stimulate bone growth over the scaffold. 19 Because use of bone morphogenetic proteins, such as BMP-2, may cause both local complications and even distant cancers, 22,23 finding other osteoinductive agents that can be used to promote bone growth in association with printed scaffolds presents a challenge.…”

The Roles of Bone Morphogenetic Proteins and Their Signaling in the Osteogenesis of Adipose-Derived Stem Cells

“…For example, a HA/btricalcium phosphate (b-TCP) scaffold that can facilitate the sustained release of BMP-2 over a 20-day period has been shown to significantly augment the osteogenic differentiation of ASCs in vitro. 46 In addition, many other scaffolds with similar properties have shown promise in this type of application, for example, a poly (DL-lactic-coglycolic acid) (PLGA) scaffold with a fibrin/hyaluronic acid coating 47 and a gelatin/b-TCP scaffold. 48 These slow-release systems can stimulate osteogenic differentiation, extracellular matrix deposition, maturation, and mineralization of ASCs.…”