Abstract
Bone tissue has an exceptional quality to regenerate to native tissue in response to injury. However, the fracture repair process requires mechanical stability or a viable biological microenvironment or both to ensure successful healing to native tissue. An improved understanding of the molecular and cellular events that occur during bone repair and remodeling has led to the development of biologic agents that can augment the biological microenvironment and enhance bone repair. Orthobiologics, including stem cells, osteoinductive growth factors, osteoconductive matrices, and anabolic agents, are available clinically for accelerating fracture repair and treatment of compromised bone repair situations like delayed unions and nonunions. Preclinical and clinical studies using biologic agents like recombinant bone morphogenetic proteins have demonstrated an efficacy similar or better than that of autologous bone graft in acute fracture healing. A lack of standardized outcome measures for comparison of biologic agents in clinical fracture repair trials, frequent off-label use, and a limited understanding of the biological activity of these agents at the bone repair site have limited their efficacy in clinical applications.
Highlights
Fracture healing involves a well-orchestrated cascade of molecular and cellular events that recapitulate the process of embryonic endochondral bone formation and results in formation of new bone across the fracture site
Successful regeneration of bone involves the interplay of four critical elements: osteoinductive growth factors, stem cells that respond to osteoinductive signals, an intact vascular supply, and, lastly, a scaffold that supports cellular attachment, proliferation, and ingrowth [3,4]
In a preclinical study in our laboratory, we found that the stem cell concentration in healthy bone marrow donors ranged between 64 and 2,993 colony-forming units (CFU)-F/mL and that an average seven-fold increase in the CFU/mL can be obtained following concentration of bone marrow by using a commercial centrifuge [26]
Summary
Fracture healing involves a well-orchestrated cascade of molecular and cellular events that recapitulate the process of embryonic endochondral bone formation and results in formation of new bone across the fracture site. There is a need to Successful regeneration of bone involves the interplay of four critical elements: osteoinductive growth factors (induce differentiation of stem cells to osteoblasts), stem cells that respond to osteoinductive signals (osteogenic), an intact vascular supply, and, lastly, a scaffold that supports cellular attachment, proliferation, and ingrowth (osteoconductive matrix) [3,4]. An improved understanding of the molecular and cellular events that occur during bone repair and remodeling has led to the development of biologic therapies that enhance bone repair in fractures and nonunions. The purpose of this article is to provide a comprehensive review of the biologic agents that can enhance bone repair and either are clinically available or are being assessed in clinical trials
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