PerspectiveBone voyage: An expedition into the molecular and cellular parameters affecting bone graft fate
Introduction
When the skeleton sustains damage, the basic challenge that faces the host is to perceive the injury and then repair the defect as quickly as possible. This is accomplished by recruiting skeletal progenitor cells to the injury site and by stimulating their proliferation. Once a sufficient population has been generated, the next task is to decelerate proliferation and induce differentiation of progenitor cells into osteoblasts. In most cases, this series of events proceeds unimpeded. There are, however, situations where bone repair is delayed or altogether arrested, cases where disease has left behind a cavity that weakens a skeletal element, or scenarios where degenerative processes compromise the stability of a joint. Orthopaedic and trauma surgeons can attest to the fact that these situations are not as infrequent as one would hope [1], [2], and they must oftentimes resort to additional treatments to augment or accelerate bone regeneration. For these cases, the most frequently employed course of action is bone grafting. For example, 8% of all fractures, 7% of spinal disorders, and an astounding 70% of benign tumors require some sort of bone grafting procedure [3], [4], [5].
Most bone grafts performed today are autologous; that is, they are derived from a patient's own skeletal tissues. While there are certain advantages to this source of bone graft material (the most obvious being the lack of any immunogenic response), there are also obvious disadvantages. For example, if the patient has an underlying disease state that compromises their skeleton, clinicians are oftentimes reluctant to use autologous sources. There are other potential complications as well: donor site morbidity, risk of infection, and inadequate bone stock are frequently cited reasons for turning to other sources of bone graft material. Allogeneic grafts (a.k.a. allografts) are derived from cadaveric sources and can be obtained in any amount or shape [6], [7] but their obvious shortcomings include the lack of skeletal progenitor cells in the graft material, and the potential for an immune reaction [8]. For these reasons, clinicians typically turn to autologous sources. But bone grafts are not always as successful as they should be, or that we hope they will be, and it is this pertinent issue which will be the focus of our perspective. We begin with a seemingly simple inquiry: just where does the graft go, when the bone grafting is done?
Section snippets
What is in a graft?
The fate of the graft depends in large part on which component of the transplant you are interested in. Mineralized matrix is always incorporated in a bone graft but to varying amounts depending on the origin of the graft. For example, when the graft is taken from the bone marrow cavity then small trabeculae are incorporated into the transplanted tissue. When mechanical stability is required then the matrix is comprised of whole cortical bone [5]. Experimental data seem to indicate that
Exogenous factors: can they enhance graft osseointegration?
A number of strategies have been employed to improve the osteogenic capacity of bone grafts. For example, bone marrow aspirates or platelet-rich plasmas are oftentimes added to the graft material in hopes of increasing the number of skeletal stem or progenitor cells [15], [16]. When bone marrow or platelet-rich plasma augmentation is contraindicated (usually because of an underlying disease state) surgeons may resort to the addition of growth factors. Two classes of growth factors that are
Graft sources: all bones are not created equal
Whether it is the coccyx or the crista galli, visual inspection of the skeleton will lead an astute observer to conclude that all osseous tissues look remarkably similar (Fig. 1). This summation will be bolstered by histological analyses, which show equivalent staining of mineralized tissues in the head, the limbs, and the spine (Fig. 1). Even molecular analyses indicate that, once cells commit to a chondrogenic or osteogenic lineage they differentiate using the same molecular machinery [28].
Heterotopic versus homotopic grafts: same or different?
Depending upon the recipient site, autologous bone grafts may be homotopic (e.g., the embryonic origin of the graft is the same as the embryonic origin of the recipient site) or they may be heterotopic (the graft's embryonic origin differs from that of the recipient site). For example, bone harvested from the iliac crest may be used in a spinal fusion; this constitutes a homotopic graft because the grafted cells and matrix originates from the mesoderm-derived pelvis, and is placed into a
No graft is an island: the contribution of the wound environment to bone repair
Whether in the cranial skeleton or elsewhere in the body, bone grafts do not exhibit biological activity in isolation. Graft survival is intimately dependent upon the host site providing a supportive milieu that allows graft survival, proliferation and ultimately, differentiation. For example, the host site must support the development of a neovasculature that provides oxygen and nutrients essential for graft survival [56]. Injured cells at the recipient site also release cytokines that support
What is the fate of the graft?
Do skeletal progenitor cells in a graft remain at the recipient site, where they differentiate into bone to heal a defect? If this is the case then the more progenitor cells contained within a graft, the better the chances are that the graft will heal the injury. Or do the grafted cells and transplanted bone matrix stimulate host cells to proliferate and then differentiate into osteoblasts to regenerate the bone? If this is the case then the osteogenic potential of a graft could be improved
Conclusions
What happens to grafted cells seems to depend on their embryonic origin, the inclusion of skeletal progenitor cells, and the integrity of the recipient site but which factors are most important remains to be determined (Fig. 3). And this is where future research would have the greatest impact on improving the outcome of bone grafts. In particular, studies should be focused on the understanding of the fate of transplanted osteoprogenitor cells, and how they contribute to the osseointegration.
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2019, Journal of Cranio-Maxillofacial SurgeryCitation Excerpt :Laird (Laird et al., 2003) also suggested that most of a bone graft is reduced and replaced by newly formed bone. Helms (Helms et al., 2007) carried out a literature review on the bone graft integration process after implantation. He reported several studies describing grafted cells becoming osteoblastic cells, or secreting factors that induced new osteogenesis.
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2014, BoneCitation Excerpt :By genetic cell lineage labeling studies [24], we established that adult skeletal stem cells arise from the cranial neural crest and the mesoderm [23]. Although both stem cell populations give rise to cartilage and bone, they do not appear to be functionally equivalent: Neural crest-derived skeletal progenitor cells, which occupy the first branchial arch (Figs. 1A,B) and give rise to the bones and cartilages of the upper and lower jaws (Figs. 1C–F) exhibit robust plasticity compared to mesoderm-derived progenitor cells, most notably in bone grafting assays [25]. Our initial hypothesis was that implant osseointegration in the tibia would be equivalent to implant osseointegration in the maxilla.
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