Current insights on the regenerative potential of the periosteum: molecular, cellular, and endogenous engineering approaches

Abstract

While century old clinical reports document the periosteum's remarkable regenerative capacity, only in the past decade have scientists undertaken mechanistic investigations of its regenerative potential. At a Workshop at the 2012 Annual Meeting of Orthopaedic Research Society, we reviewed the molecular, cellular, and tissue scale approaches to elucidate the mechanisms underlying the periosteum's regenerative potential as well as translational therapies engineering solutions inspired by its remarkable regenerative capacity. The entire population of osteoblasts within periosteum, and at endosteal and trabecular bone surfaces within the bone marrow, derives from the embryonic perichondrium. Periosteal cells contribute more to cartilage and bone formation within the callus during fracture healing than do cells of the bone marrow or endosteum, which do not migrate out of the marrow compartment. Furthermore, a current healing paradigm regards the activation, expansion, and differentiation of periosteal stem/progenitor cells as an essential step in building a template for subsequent neovascularization, bone formation, and remodeling. The periosteum comprises a complex, composite structure, providing a niche for pluripotent cells and a repository for molecular factors that modulate cell behavior. The periosteum's advanced, "smart" material properties change depending on the mechanical, chemical, and biological state of the tissue. Understanding periosteum development, progenitor cell-driven initiation of periosteum's endogenous tissue building capacity, and the complex structure-function relationships of periosteum as an advanced material are important for harnessing and engineering ersatz materials to mimic the periosteum's remarkable regenerative capacity.

Figure 1. Development of the periosteum and its contribution to bone repair

Stages of long bone development including formation of the initial mesenchymal condensations, followed by the segregation of cartilage (pink) and perichondrium (blue), vascular invasion and replacement of hypertrophic cartilage by bone and bone marrow. Osteoblasts within periosteum (green), bone marrow and endosteum (brown) are derived from the embryonic perichondrium. In the adult, after bone injury, cells that form cartilage and bone in the fracture callus are recruited locally from periosteum, bone marrow, blood vessels (pericytes) and potentially other adjacent tissues such as muscle and fat. Cellular contribution from systemic sources is minimal (red dots).

Figure 2. One stage bone transport model to elucidate and to harness the regenerative capacity of the periosteum

Proximal to the defect zone, the periosteum is peeled back gently and the denuded bone underneath is osteotomized, transported and docked distally, filling the original defect zone and creating a new, more proximal defect. The periosteum which was peeled back is then sutured in place, in situ, forming a sleeve around the new, haematoma filled defect. The entire construct is stabilized by an interlocked intramedullary nail. Figure after [86].