Silk fibroin-based complex particles with bioactive encrustation for bone morphogenetic protein 2 delivery.
Application of bone morphogenetic protein 2 (BMP-2) currently faces its challenges, and its efficacy of delivery has to be improved. The proper dosage of the powerful bioactive molecule is still under discussion and needs to be investigated further. In this work, pure silk fibroin particles and particles with calcium carbonate encrustation (complex particles) are designed, developed, and functionalized by BMP-2. These are used to deliver the bioactive molecule to mesenchymal stem cells (MSCs) to induce osteogenic differentiation. Results are compared with those of control groups of BMP-2 carriers under the same condition. Silk fibroin-based particles with size and component variations are prepared by self-assembly, desolvation, and soft template formation to improve BMP-2 loading efficiency. Results show that the particles significantly enhance osteogenic differentiation of MSCs, which is evident in the high ALP enzyme activity as well as the increased level of expression of osteogenic genes. Specifically, the combination of calcium compound and BMP-2 in the silk fibroin-calcium carbonate complex particles synergistically enhances osteogenesis. Release tests and mathematical modeling are applied to describe BMP-2 dissolution profiles, and the release mechanism is based on diffusion and polymer chain relaxation. In summary, the particles show high efficacies of BMP-2 delivery, and introduction of the complex particle can progressively enhance osteogenesis.
Department of Biomedical Engineering, National University of Singapore , Singapore 117575.
Pujiang
P
Shi
Sunny A
SA
Abbah
Kushagra
K
Saran
Yong
Y
Zhang
Jun
J
Li
Hee-Kit
HK
Wong
James C H
JC
Goh
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D012831:Bombyx; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry* / Q000494:pharmacology; D001861:Bone Regeneration; D002119:Calcium Carbonate / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005349:Fibroins / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology; D046529:Microscopy, Electron, Transmission; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011817:Rabbits; D017550:Spectroscopy, Fourier Transform Infrared
D055396:Bone Morphogenetic Protein 2; D053769:Nanocapsules; D005349:Fibroins; D000469:Alkaline Phosphatase; D002119:Calcium Carbonate