期刊
JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
卷 16, 期 11, 页码 961-976出版社
WILEY
DOI: 10.1002/term.3349
关键词
biomaterials; bone regeneration; canonical Wnt; drug delivery; therapeutics
类别
资金
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01 AR077761]
- Orthoregeneration Network [20-166]
- National Institutes of Health
This article reviews methods to enhance bone formation and improve bone repair, focusing on the challenges and solutions for activating the Wnt pathway through antibody-based therapeutics, synthetic Wnt surrogates, and scaffold doping. Additionally, emerging technologies such as mRNA therapy and CRISPR technology for clinical translation are discussed.
Activation of the canonical Wingless-related integration site (Wnt) pathway has been shown to increase bone formation and therefore has therapeutic potential for use in orthopedic conditions. However, attempts at developing an effective strategy to achieve Wnt activation has been met with several challenges. The inherent hydrophobicity of Wnt ligands makes isolating and purifying the protein difficult. To circumvent these challenges, many have sought to target extracellular inhibitors of the Wnt pathway, such as Wnt signaling pathway inhibitors Sclerostin and Dickkopf-1, or to use small molecules, ions and proteins to increase target Wnt genes. Here, we review systemic and localized bioactive approaches to enhance bone formation or improve bone repair through antibody-based therapeutics, synthetic Wnt surrogates and scaffold doping to target canonical Wnt. We conclude with a brief review of emerging technologies, such as mRNA therapy and Clustered Regularly Interspaced Short Palindromic Repeats technology, which serve as promising approaches for future clinical translation.
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