A Perspective: Engineering Periosteum for Structural Bone Graft Healing

Abstract

Autograft is superior to both allograft and synthetic bone graft in repair of large structural bone defect largely due to the presence of multipotent mesenchymal stem cells in periosteum. Recent studies have provided further evidence that activation, expansion and differentiation of the donor periosteal progenitor cells are essential for the initiation of osteogenesis and angiogenesis of donor bone graft healing. The formation of donor cell-derived periosteal callus enables efficient host-dependent graft repair and remodeling at the later stage of healing. Removal of periosteum from bone autograft markedly impairs healing whereas engraftment of multipotent mesenchymal stem cells on bone allograft improves healing and graft incorporation. These studies provide rationale for fabrication of a biomimetic periosteum substitute that could fit bone of any size and shape for enhanced allograft healing and repair. The success of such an approach will depend on further understanding of the molecular signals that control inflammation, cellular recruitment as well as mesenchymal stem cell differentiation and expansion during the early phase of the repair process. It will also depend on multidisciplinary collaborations between biologists, material scientists and bioengineers to address issues of material selection and modification, biological and biomechanical parameters for functional evaluation of bone allograft healing.

Treatment of intrabony defects with modified perforated membranes in aggressive periodontitis: a 12-month randomized controlled trial

“…Periosteal cell populations modify their potential with age, with a significant increase in IL-6 mRNA expression and receptor activator of nuclear factor kappa-B ligand/osteoprotegerin ratio [6]. In vivo studies indicated that PDPCs are indispensable for bone graft healing and remodeling [7].…”

Mineralization and bone regeneration using a bioactive elastin-like recombinamer membrane

“…In an attempt to further enhance bone regeneration therapies, and taking advantage of the benefits of the periosteum, the use of periosteal grafts has emerged as an attractive strategy [7]. An ideal periosteal graft would not only provide a physical structure that facilitates osteoconduction, but also osteoinductive signals that stimulate osteogenesis and ultimately promote biomineralization [8].…”

Emerging Ideas: Engineering the Periosteum: Revitalizing Allografts by Mimicking Autograft Healing

“…Loss of osteocytes during allograft devitalization may contribute to an overall decrease in graft resorption and remodeling as compared with autograft controls [45]. Osteocytes, however, have no contribution to early osteogenesis of bone grafts [47], so we believe our approach will still enhance allograft integration and healing, even in the absence of these cells. Furthermore, by altering PEG degradation kinetics or hydrogel MSC densities we believe we can exercise temporal control over the initiation of remodeling and thereby increase early matrix production and ossification [45,48].…”

“…Allografts remain the gold standard for treating critical-sized bone defects but have slow bone formation and minimal engraftment, resulting in fibrotic nonunions and brittle fractures [44,45,47,48]. In contrast, autografts completely heal, mediated by the periosteum.…”

“…These suboptimal qualities limit cell survival and graft localization [8,10,34,45,48]. Growth factor delivery also is challenging owing to diffusion and degradation, requiring delivery of supraphysiologic concentrations [12], resulting in costly clinical applications [9,13,39,47].…”