Abstract
Difficulties in treating pseudarthrosis and critical bone defects are still evident in physicians’ clinical routines. Bone morphogenetic protein 2 (BMP-2) has shown promising osteoinductive results but also considerable side effects, not unexpected given that it is a morphogen. Thus, the bone regenerative potential of the novel selective, non-morphogenic EP4 prostaglandin receptor agonist KMN-159 was investigated in this study. Therefore, mineralized collagen type-1 matrices were loaded with different amounts of BMP-2 or KMN-159 and implanted into a 5 mm critical-sized femoral defect in rats. After 12 weeks of observation, micro-computed tomography scans were performed to analyze the newly formed bone volume (BV) and bone mineral density (BMD). Histological analysis was performed to evaluate the degree of defect healing and the number of vessels, osteoclasts, and osteoblasts. Data were evaluated using Kruskal-Wallis followed by Dunn’s post hoc test. As expected, animals treated with BMP-2, the positive control for this model, showed a high amount of newly formed BV as well as bone healing. For KMN-159, a dose-dependent effect on bone regeneration could be observed up to a dose optimum, demonstrating that this non-morphogenic mechanism of action can stimulate bone formation in this model system.
Highlights
The difficulty in treating disturbed or delayed fracture healing is still evident in the daily routine of physicians
In this study mineralized collagen matrix (MCM) scaffolds were loaded with different concentrations of rhBMP-2 or the EP4 prostaglandin receptor agonist KMN-159
Wistar rats, stabilized with an osteosynthesis plate, and augmented by an MCM scaffold functionalized with rhBMP-2 or increasing amounts of KMN-159
Summary
The difficulty in treating disturbed or delayed fracture healing is still evident in the daily routine of physicians. Pseudarthrosis, infection, and tumor excision can lead to critical bone defects that require bone replacement. Autologous bone transplantation is the gold standard in treating critical bone defects today [1]. Since autologous bone transplantation is not feasible to an unlimited extent, and because it involves a number of risks and disadvantages, new possibilities for bone replacement and osteopromotive or osteoinductive materials are being sought in various directions. Growth factors for improved bone regeneration are being investigated and used clinically [2]. The most important are the bone morphogenetic proteins (BMPs). With the exception of BMP-1, a metalloproteinase, they represent a subgroup of the transforming growth factor-β (TGF-β) family and contribute to the differentiation of mesenchymal stromal cells (MSCs) that are important for bone healing and other development-relevant processes in Biomedicines 2021, 9, 1712.
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