The role of stem cells in fracture healing and nonunion

Abstract

Nonunion and large bone defects present a therapeutic challenge to the surgeon and are often associated with significant morbidity. These defects are expensive to both the health care system and society. However, several surgical procedures have been developed to maximise patient satisfaction and minimise health-care-associated and socioeconomic costs. Integrating recent evidence into the diamond concept leads to one simple conclusion that not only provides us with answers to the "open questions" but also simplifies our entire understanding of bone healing. It has been shown that a combination of neo-osteogenesis and neovascularisation will restore tissue deficits, and that the optimal approach includes a biomaterial scaffold, cell biology techniques, a growth factor and optimisation of the mechanical environment. Further prospective, controlled, randomised clinical studies will determine the effectiveness and economic benefits of treatment with mesenchymal stem cells, not in comparison to other conventional surgical approaches but in direct conjunction with them.

The rational use of animal models in the evaluation of novel bone regenerative therapies

“…Although bone possesses endogenous self-repair mechanisms [4][5][6][7][8], in conditions such as impaired blood supply, excessive damage to the periosteum, inadequate immobilization, infection at the affected area, mineral and vitamin deficiencies, underlying diseases and side effects of certain medications and radiation, the enhancement of the regenerative processes is necessary to ensure the rapid and adequate restoration of skeletal functions [9][10][11]. The standard therapy to treat bone fractures/defects includes mechanical support either via cast and/or mechanical devices (e.g.…”

“…Under appropriate conditions MPCs could be differentiated into a variety of mesenchymal tissues such as bone, cartilage, tendon, ligament, marrow stroma, muscle, fat and dermis [4,[49][50][51][52][53]. To induce fracture healing, MPCs are expanded ex vivo prior to their autologous grafting to the fracture site and differentiated into osteogenic lineages to promote bone regeneration [9,54]. Such cell-based strategy approaches have been used to demonstrate that autologous bone marrow-derived MPC transplantation was superior compared to unloaded scaffold [5,7].…”

Autologous Bone Marrow Stem Cells combined with Allograft Cancellous Bone in Treatment of Nonunion

“…Therefore, investigations are needed to provide a safe and effective alternative. Tissue engineering has appeared to be a very promising technique in several regenerative applications in different anatomic regions (Fayaz et al, 2011;Hernigou et al, 2006;Jäger et al, 2011;Pacini, 2014). Indeed, the combination of cells and scaffolds could represent the optimal solution for the manage-…”

“…As is widely accepted, the "diamond concept" of bone fracture healing is applied to treating nonunion (Fayaz et al, 2011;Giannoudis et al, 2007;Gómez-Barrena et al, 2015). A triangular-shaped complex of interactions between the potent osteogenic cell populations, the osteoinductive stimulus and the osteoconductive matrix scaffolds are extensively studied and applied in search for the optimal grafting material (Giannoudis et al, 2007;Khan et al, 2011;Virk and Lieberman, 2012).…”

“…A triangular-shaped complex of interactions between the potent osteogenic cell populations, the osteoinductive stimulus and the osteoconductive matrix scaffolds are extensively studied and applied in search for the optimal grafting material (Giannoudis et al, 2007;Khan et al, 2011;Virk and Lieberman, 2012). Mechanical stability is added to the diamond model as a crucial factor for bone healing, and essential for the formation of a callus that bridges the fracture site allowing loads to be transmitted across the fracture line (Fayaz et al, 2011;Hernigou et al, 2005b).…”