Osteostimulation scaffolds of stem cells: BMP‐7‐derived peptide‐decorated alginate porous scaffolds promote the aggregation and osteo‐differentiation of human mesenchymal stem cells

Abstract

The scaffolds for stem cell-based bone tissue engineering should hold the ability to guide stem cells osteo-differentiating. Otherwise, stem cells will differentiate into unwanted cell types or will form tumors in vivo. Alginate, a natural polysaccharide with great biocompatibility, was widely used in biomedical applications. However, the limited bioactivity and poor osteogenesis capability of pristine alginate hampered its further application in tissue engineering. In this work, a bone forming peptide-1 (BFP-1), derived from bone morphogenetic protein-7, was grafted to alginate polymer chains to prepare peptide-decorated alginate porous scaffolds (pep-APS) for promoting osteo-differentiation of human mesenchymal stem cells (hMSCs). SEM images of pep-APS exhibited porous structure with about 90% porosity (pore size 100-300 μm), which was appropriate for hMSCs ingrowth. The adhesion, proliferation and aggregation of hMSCs grown on pep-APS were enhanced in vitro. Moreover, pep-APS promoted the alkaline phosphatase (ALP) activity of hMSCs, and the osteo-related genes expression was obviously up-regulated. The immunochemical staining and western blot analysis results showed high expression level of OCN and Col1a1 in the hMSCs grown on pep-APS. This work provided a facile and valid strategy to endow the alginate polymers themselves with specific bioactivity and prepare osteopromoting scaffold with enhanced osteogenesis ability, possessing potential applications in stem cell therapy and regenerative medicine.

Modulating Alginate Hydrogels for Improved Biological Performance as Cellular 3D Microenvironments

“…Similarly, RGD/BMP-2 KE alginate hydrogels were able to promote osteogenesis in MSC, as observed by the upregulation of Smad signaling pathway, osteopontin overexpression and increased mineral deposition, whereas the same response was not observed for RGD/DWIVA hydrogels (Madl et al, 2014 ). Likewise, Yang et al ( 2018 ) covalently incorporated BMP-7 derived peptide BFP-1 by carbodiimide chemistry into alginate to develop a lyophilized, porous scaffold capable of inducing MSC osteo-differentiation. The authors observed a significant increase in ALP activity and expression of bone-related genes [osteocalcin, collagen 1, runt-related transcription factor 2 (Runx2) and ALP] and proteins (osteocalcin and collagen 1) in MSC seeded onto BFP-1 modified alginate as opposed to pristine alginate scaffolds (Yang et al, 2018 ).…”

“…Likewise, Yang et al ( 2018 ) covalently incorporated BMP-7 derived peptide BFP-1 by carbodiimide chemistry into alginate to develop a lyophilized, porous scaffold capable of inducing MSC osteo-differentiation. The authors observed a significant increase in ALP activity and expression of bone-related genes [osteocalcin, collagen 1, runt-related transcription factor 2 (Runx2) and ALP] and proteins (osteocalcin and collagen 1) in MSC seeded onto BFP-1 modified alginate as opposed to pristine alginate scaffolds (Yang et al, 2018 ).…”

RETRACTED ARTICLE: Degradable poly-L-lysine-modified PLGA cell microcarriers with excellent antibacterial and osteogenic activity

“…Bone morphogenetic protein 7 (BMP-7) is a growth factor that has strong osteoinductivity and plays an important role in promoting bone tissue repair. Recent studies have indicated that BMP-7 can stimulate mesenchymal stem cells to differentiate into osteoblasts, and BMP-7 has been used in the treatment of facial bone defects, large bone defects, and spinal fusion [19][20][21]. However, as a cytokine, BMP-7 shows the disadvantage that cytokines generally exhibit, i.e.…”

Technological Advances of 3D Scaffold-Based Stem Cell/Exosome Therapy in Tissues and Organs

“…Natural materials include collagen ( Chang et al, 2011 ), gelatin ( Chang et al, 2020 ), fibrin ( Rabbani et al, 2017 ), silk fibroin ( Qing et al, 2018 ), alginate ( Yang et al, 2018 ), gellan gum, hyaluronic acid (HA) ( Yazdani et al, 2019 ), chitosan ( Kim et al, 2016 ), Matrigel ( Wang et al, 2020b ); while synthetic polymer materials include poly caprolactone (PCL) ( Zhang et al, 2017 ), polydimethylsiloxane (PDMS) ( McKee et al, 2017 ), polyethylene oxide (PEO) ( Evrova et al, 2016 ), polylactic acid (PLA) ( Gandolfi et al, 2020 ), poly lactic acid-glycolic acid (PLGA) ( Swanson et al, 2020 ), polyvinyl alcohol (PVA) ( Kalachaveedu et al, 2020 ), polyethylene glycol (PEG), tribasic calcium phosphate (TCP) ( Ying et al, 2020 ). Biomaterials used for 3D bioprinting are called “bio-inks.”…”

“… Yang et al (2018) reported that peptide-modified porous alginate scaffolds enhanced the adhesion, proliferation, and aggregation of MSCs in vitro . The alginate polymers also exhibited complex bioactivity and functioned as an osteogenesis-promoting scaffold.…”