A matrix for phalanx regeneration in mice

Extracellular matrix particles, made from the protein scaffold of tissue, increased new bone volume after middle phalanx amputation in adult mice

On August 6, Yingqing Liu's team published a bioRxiv study describing an experiment in adult mice. After amputating the digit tip and the distal part of the middle phalanx, the researchers preserved the soft tissues around the wound and placed extracellular matrix particles inside it. After 10 to 35 days, new bone volume was greater than after the same operation without the particles. In a separate series that included the protein BMP2, the increase was larger.

Mouse digit tips have a limited capacity for regeneration. After a standard amputation of the middle phalanx, P2, new bone merely thickens the remaining segment. P2 amputation can therefore be used to test whether adult tissue begins to build new bone after injury.

The team removed the digit tip and the distal part of P2 in female mice aged 6 to 8 weeks. They preserved the skin and other soft tissues around the bone and wrapped them around the surgical site. The authors call this procedure soft tissue preserving amputation (SPA). In the control version of the procedure, no material was added, but new bone still formed.

The researchers also placed particles of extracellular matrix, a dried protein scaffold derived from porcine urinary bladder, into the wound. The preserved soft tissues held the particles in place. The authors write:

“The preserved soft tissues not only retain the solid particles but also stimulate bone regeneration.”

Micro-CT, a three-dimensional X-ray imaging method for mineralized tissue, was performed on days 10, 21, and 35. New bone volume was greater in the matrix particle group than in the SPA control group. The series included three biological replicates. By day 35, this bone had a lower mean mineral density, and the three-dimensional images showed separate loose bone fragments.

In a second series, the researchers moved the amputation site to the middle of P2 and added BMP2, a protein involved in cartilage and bone formation, to the matrix particles. After 30 to 35 days, the volume of new bone exceeded that of an intact P2, and its length increased. The series included three biological replicates.