Elucidating multiscale periosteal mechanobiology: a key to unlocking the smart properties and regenerative capacity of the periosteum?

Abstract

The periosteum, a thin, fibrous tissue layer covering most bones, resides in a dynamic, mechanically loaded environment. The periosteum also provides a niche for mesenchymal stem cells. The mechanics of periosteum vary greatly between species and anatomical locations, indicating the specialized role of periosteum as bone's bounding membrane. Furthermore, periosteum exhibits stress-state-dependent mechanical and material properties, hallmarks of a smart material. This review discusses what is known about the multiscale mechanical and material properties of the periosteum as well as their potential effect on the mechanosensitive progenitor cells within the tissue. Furthermore, this review addresses open questions and barriers to understanding periosteum's multiscale structure-function relationships. Knowledge of the smart material properties of the periosteum will maximize the translation of periosteum and substitute periosteum to regenerative medicine, facilitate the development of biomimetic tissue-engineered periosteum for use in instances where the native periosteum is lacking or damaged, and provide inspiration for a new class of smart, advanced materials.

FIG. 1.

Histological images of periosteum from skeletally mature bone (A) of an aged human and middle aged sheep (B). (A) In a cross section of the mid-diaphysis of the human tibia (patient age at death: 69 years). Image used with permission. (B) In a cross section of the mid-diaphysis of the ovine femur (∼4 years of age). Image adapted and used with permission. CL, cambium layer; FL, fibrous layer. Color images available online at www.liebertpub.com/teb

FIG. 2.

Postnatal bone healing recapitulates processes of bone formation in utero. Mesenchymal condensation is a seminal event marking the initiation of skeletogenesis (blue dotted square in schematic). By tracking relative gene expression, one can assess the relative stage and/or path of lineage commitment for uncommitted pluripotent cell-like periosteum-derived cells. Red font depicts gene markers for pre-, peri-, and postmesenchymal condensation. Magenta font indicates gene markers for the formation of cell–cell and cell–matrix adhesions, key for self-aggregation of cells and emergent tissue architecture. Mesenchymal stem cells can commit to chondrogenic (orange), osteogenic (blue), and adipogenic (green) path lineages. Figure adapted and used with permission. Color images available online at www.liebertpub.com/teb

FIG. 3.

Characterization of periosteum's mechanical properties. (A) Periosteal shrinkage as measured previously. The left and top edges are shown in blue and the right and bottom edges are shown in green. Image correlation was used to determine change in axial length (difference between top and bottom edges) and change in circumferential length (difference between left and right edges). (B, C) The elastic modulus of ovine femoral periosteum was determined using mechanical testing and high-resolution strain mapping. (D) Periosteal strain is calculated as the change in length of periosteum samples from when they are attached to bone to their length initially upon removal from the bone. Prestress is calculated by multiplying the change in strain by the elastic modulus of the tissue. Portions of this figure used with permission. Color images available online at www.liebertpub.com/teb

FIG. 4.

Stress–strain properties of ovine femoral periosteum removed from the (A) axial and (B) circumferential orientations of the bone. Axial periosteum exhibits a high stiffness (E=25.67 MPa) in the linear region of the stress–strain curve. Used with permission from Ref. Color images available online at www.liebertpub.com/teb