Cell-permeable bone morphogenetic protein 2 facilitates bone regeneration by promoting osteogenesis.

Autor:	Kang M; Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul, 03929, South Korea., Lee S; Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul, 03929, South Korea., Seo JP; College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University, Jeju, 63243, South Korea., Lee EB; College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University, Jeju, 63243, South Korea., Ahn D; Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul, 03929, South Korea., Shin J; Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul, 03929, South Korea., Paik YK; Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul, 03929, South Korea., Jo D; Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul, 03929, South Korea.
Jazyk:	angličtina
Zdroj:	Materials today. Bio [Mater Today Bio] 2024 Feb 01; Vol. 25, pp. 100983. Date of Electronic Publication: 2024 Feb 01 (Print Publication: 2024).
DOI:	10.1016/j.mtbio.2024.100983
Abstrakt:	The use of the FDA-approved osteoinductive growth factor BMP2 is widespread for bone regeneration. However, its clinical application has been hindered by limitations in cell permeability and a short half-life in circulation. To address this issue, we have developed a modified version of BMP2, referred to as Cell Permeable (CP)-BMP2, which possesses improved cell permeability. CP-BMP2 incorporates an advanced macromolecular transduction domain (aMTD) to facilitate transfer across the plasma membrane, a solubilization domain, and recombinant human BMP2. Compared to traditional rhBMP2, CP-BMP2 exhibits enhanced cell permeability, solubility, and bioavailability, and activates Smad phosphorylation through binding to BMP receptor 2. The effectiveness of CP-BMP2 was evaluated in three animal studies focusing on bone regeneration. In the initial study, mice and rabbits with critical-size calvarial defects received subcutaneous (SC) injections of CP-BMP2 and rhBMP2 (7.5 mg/kg, 3 injections per week for 8 weeks).Following 8 weeks of administration, CP-BMP2 demonstrated a remarkable 65 % increase in bone formation in mice when compared to both the vehicle and rhBMP2. Moreover, rabbits exhibited faster bone formation, characterized by a filling pattern originating from the center. In a subsequent study involving injured horses, hind limb bones treated with CP-BMP2 exhibited an 85 % higher bone regeneration rate, as evidenced by Micro-CT results, in contrast to horses treated with the vehicle or rhBMP2 (administered at 150 μg/defect, subcutaneously, once a week for 8 weeks, without a scaffold). These results underscore the potential of CP-BMP2 to facilitate rapid and effective healing. No noticeable adverse effects, such as ectopic bone formation, were observed in any of the studies. Overall, our findings demonstrate that CP-BMP2 holds therapeutic potential as a novel and effective osteogenic agent. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 The Authors.)
Databáze:	MEDLINE
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