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Mouse Digit Tip Regeneration Is Mechanical Load Dependent
Author(s) -
Dolan Connor P,
Imholt Felisha,
Yang TaeJung,
Bokhari Rihana,
Gregory Joshua,
Yan Mingquan,
Qureshi Osama,
Zimmel Katherine,
Sherman Kirby M,
Falck Alyssa,
Yu Ling,
Leininger Eric,
Brunauer Regina,
Suva Larry J,
Gaddy Dana,
Dawson Lindsay A,
Muneoka Ken
Publication year - 2022
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.4470
Subject(s) - regeneration (biology) , blastema , numerical digit , wound healing , bone healing , anatomy , biomedical engineering , microbiology and biotechnology , biology , medicine , surgery , arithmetic , mathematics
Amputation of the mouse digit tip results in blastema‐mediated regeneration. In this model, new bone regenerates de novo to lengthen the amputated stump bone, resulting in a functional replacement of the terminal phalangeal element along with associated non‐skeletal tissues. Physiological examples of bone repair, such as distraction osteogenesis and fracture repair, are well known to require mechanical loading. However, the role of mechanical loading during mammalian digit tip regeneration is unknown. In this study, we demonstrate that reducing mechanical loading inhibits blastema formation by attenuating bone resorption and wound closure, resulting in the complete inhibition of digit regeneration. Mechanical unloading effects on wound healing and regeneration are completely reversible when mechanical loading is restored. Mechanical unloading after blastema formation results in a reduced rate of de novo bone formation, demonstrating mechanical load dependence of the bone regenerative response. Moreover, enhancing the wound‐healing response of mechanically unloaded digits with the cyanoacrylate tissue adhesive Dermabond improves wound closure and partially rescues digit tip regeneration. Taken together, these results demonstrate that mammalian digit tip regeneration is mechanical load‐dependent. Given that human fingertip regeneration shares many characteristics with the mouse digit tip, these results identify mechanical load as a previously unappreciated requirement for de novo bone regeneration in humans. © 2021 American Society for Bone and Mineral Research (ASBMR).