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Healing of a critical size defect remains still a challenge, because without intervention it ends in a delayed healing or nonunion (Mathon et al., 1998). Treatment with an autologous cancellous bone transplant, the gold standard, often works well, but also possesses many disadvantages (Jäger et al., 2005a; Rompe et al., 2004).
Thus many new bone substitutes, used as scaffolds, are being developed. These scaffolds shall “guide” and thereby promote the bone healing process. The mechanical properties of the scaffold, such as the microstiffness are very important for osteoregeneration and have to be tailored in an optimal manner to address the needs of the healing bone (Chatterjee et al., 2010; Engler et al., 2006; Huebsch et al. 2010).
This study examined, for the first time, the influence of the microstiffness of the scaffold material on the healing outcome in vivo. The microstiffness affects the resistance a cell feels when it binds to the extracellular matrix.
Therefore, two gelatin scaffolds were developed at the Helmholtz Centrum Geesthacht.
The mechanical properties of these scaffolds only differ in their microstiffness.
Gelatin scaffold 1 had a microstiffness of 100 kPa and Gelatin scaffold 2 had a microstiffness of 1200 kPa. In 24 rats, which were randomized and divided into three groups, a five millimeter defect at the os femoris was created.
This defect was stabilized with a unilateral external fixator and was filled in the first group with the softer scaffold (gelatin scaffold group 1), while the second group received the stiffer scaffold (gelatin scaffold group 2), and the third group received a xenograft of cancellous bone (positive control group). Biweekly radiographs and in vivo micro-computer tomography scans were prepared. After six weeks the animals were euthanized, the bones were obtained and evaluated histologically. Radiologic and histological analysis revealed that no animals from the two gelatin scaffold groups showed a bony bridging after six weeks. However, one animal from the gelatin scaffold group 2 shows a cartilaginous bridging and another animal from this group had almost achieved bony consolidation.
The remaining animals from both gelatin scaffold groups indicated some signs of delayed healing, such as decreased vascularisation, rounded ends of the callus or prolapsed muscle into the osteotomy gap. Even in the cancellous bone graft group, no animal had a bony bridging of the gap after six week. The cancellous bone graft was clearly visible in the gap and partly already consolidated into the newly formed bony callus.
Signs of delayed healing were hardly observed in this group. The quantitative radiologic and histological measurements showed that the gelatin scaffold group 2 had significantly higher bone and cartilage formations in the new formed callus than the gelatin scaffold group 1. Also, the cancellous bone graft group had significantly higher new bone and cartilage callus tissue formation than the gelatin scaffold group 1. However, there were no quantitative differences in the amount of bone or cartilage tissue formation between the gelatin scaffold group 2 and the cancellous bone graft group.
That implies that the scaffold with the higher microstiffness not only better supported the bone healing than the scaffold with the lower microstiffness, it even supported a similar degree of healing to that of the cancellous bone graft.