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WIREs Nanomed Nanobiotechnol
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Osteogenic growth peptide and its use as a bio‐conjugate in regenerative medicine applications

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For nearly 2000 years, biomaterials have been used as damaged tissue implants. A field that started with wood and gold tissue replacements has evolved into an advanced science which combines ideas of cellular biology, engineering, and synthetic chemistry to produce bioresorbable materials capable of directing specific cell responses. With the overwhelming number of failed bone defect repairs every year, bone tissue engineering has become an important area of study. Both naturally occurring and synthetic polymeric materials have shown promising results for bone regeneration with their wide range of mechanical and degradation properties. Despite their favorable properties, these materials are limited by their lack of the biological cues necessary for enhanced bone formation and osteogenic differentiation. For this reason, naturally occurring growth factors, such as osteogenic growth peptide (OGP), have been studied for use in bone tissue engineering constructs to elicit more efficient bone healing. OGP functionalization of bioresorbable polymers has been shown to enhance regeneration of bone and osteogenic differentiation of stem cells in defect models. Vast improvements in bone tissue engineering constructs have been made possible through the use of OGP as a functional bio‐conjugate. As this field continues to expand, the hopes of overcoming the limitations of current bone defect repair treatment methods is becoming a reality. WIREs Nanomed Nanobiotechnol 2016, 8:449–464. doi: 10.1002/wnan.1376 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Biology-Inspired Nanomaterials > Peptide-Based Structures
OGP is a naturally occurring 14‐mer peptide with an active subunit from amino acids 10 to 14. The accessory domain functions as the portion of the peptide necessary for binding to α2M binding protein for regulation of OGP serum concentration and protection against proteolytic cleavage. The active domain is cleaved after dissociation from α2M binding protein, and drives mitogenic activity and differentiation of osteoblast cell lines. (Reprinted with permission from Ref . Copyright 2002 Wiley Periodicals Inc)
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Effect of OGP functionalization on bone differentiation gene expression for hMSCs after 2 and 4 weeks in vitro as observed using qRT‐PCR. (a) GAPDH was used as the endogenous reference gene for normalization of RUNX2, BSP, and OSC expression. SyberGreen primers were used for all qRT‐PCR experiments. (b) The transcription factor, RUNX2, plays a crucial role in osteoblast differentiation for hMSCs. Expression of RUNX2 is one of the earliest signs of hMSC. Compared to the controls there is ~2.5 fold increase in RUNX2 expression for both OGP‐functionalized poly(1‐PHE‐6) scaffolds with 250–400 µm pore sizes, suggesting an early enhancement of osteogenic differentiation. (c) BSP can also be used to track differentiation speed of hMSCs. From 2w to 4w, there is a decrease in BSP expression for all experimental scaffolds, suggesting hMSCs have reached the osteoprogenitor stage and are progressing into the mature osteoblast stage by 4w. (d) OSC is a gene only expressed during the mature osteoblast phase. The data shows a 2–3 fold increase in OSC expression at 4w for OGP‐functionalized poly(1‐PHE‐6) scaffolds with 250–400 µm pores. This suggests the OGP functionalization and larger pore sizes have contributed to a faster hMSC osteogenic differentiation. All fold differences were calculated with respect to the control poly(1‐PHE‐6) 100–250 and 250–400 µm scaffolds. * indicates P value <0.05 for 2 and 4w OGP‐functionalized scaffolds and controls. ** indicates P value <0.05 for 2 and 4w crosslinked and non‐crosslinked OGP‐functionalized scaffolds of the same pore size. *** indicates P value <0.05 for 2 and 4w 100–250 µm and 250–400 µm pore sizes of OGP‐functionalized scaffolds. (Reprinted with permission from Ref . Copyright 2015 American Chemical Society)
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OGP signaling for proliferation starts with the endogenous release of OGP from the cell following bone ablation. The OGP binding protein, α2M non‐covalently binds to OGP in serum to prevent premature proteolysis and to regulate a steady state concentration. OGP dissociates from α2M and is then proteolytically cleaved to generate the active OGP[10–14] subunit. OGP[10–14] binds to the Gi protein cell receptor to promote mitogenic activity of osteoblast cell lines via the MAPK pathway. (Reprinted with permission from Ref . Copyright 2001 Wiley InterScience)
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Therapeutic Approaches and Drug Discovery > Emerging Technologies
Biology-Inspired Nanomaterials > Peptide-Based Structures
Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement

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