Abstract
Bone fractures represent a significant medical morbidity among aged population with osteoporosis. Bone morphogenetic proteins (BMPs) are suggested to have therapeutic potential to enhance fracture healing in such patients. Though BMP-mediated fracture healing has been well-documented in preclinical models, there has been no clinical study that demonstrated unequivocally that indeed a BMP when presented with an appropriate scaffold could provide basis for robust outcome for delayed or non-union diaphyseal bone fractures. This review presents a comprehensive insight towards the existing knowledge on the role of BMP signaling in bone formation and maintenance. Also therapeutic options based on BMP biology are discussed.A novel osteoinductive autologous bone graft substitute (ABGS) aimed to accelerate bone regeneration was developed and is currently being tested in the clinical setting. It comprises of a biologically compatible autologous carrier made from the patient’s peripheral blood (autologous blood coagulum, ABC) and of rhBMP6 as an active ingredient. Such formulation circumvents the use of animal-derived materials, significantly limits inflammatory processes common in commercial bone devices and renders the carrier flexible, malleable, and injectable ensuring the ease of use. The ongoing clinical trials result will provide more detailed insights into the safety, tolerability, pharmacokinetics, and bone healing effects in humans and potentially provide novel and safe therapeutic options for bone repair.
Highlights
Bone fracture repairBone is one of the few tissues in the adult human body with the ability to repair, regenerate, and restore function spontaneously upon fracture
Bone healing process is a prototype for tissue engineering since it involves signal, cells and substratum, and is traditionally divided into three stages: an early inflammatory and cell recruitment stage, intermittent cell differentiation and formation of new bone and late bone remodeling and formation of defined cortices
In cases where normal bone fracture healing is not achieved, it is advisable to apply Bone morphogenetic proteins (BMPs) containing substratum to induce the formation of new bone locally and assure the bridging [3]
Summary
Bone is one of the few tissues in the adult human body with the ability to repair, regenerate, and restore function spontaneously upon fracture. Bone healing process is a prototype for tissue engineering since it involves signal, cells and substratum, and is traditionally divided into three stages: an early inflammatory and cell recruitment stage (callus formation), intermittent cell differentiation and formation of new bone (fracture repair) and late bone remodeling and formation of defined cortices (restoration). Most of the fractures heal in time without any consequences, when fractures are compounded or open it can result in indirect or secondary healing due to incomplete mechanical stability of broken fragments in mixed intramembranous and endochondral ossification subsequent to callus formation. In cases where normal bone fracture healing is not achieved, it is advisable to apply BMP containing substratum to induce the formation of new bone locally and assure the bridging [3]. Plasma BMP values were determined in a single time-point, disabling the insight into potential difference between healing phases
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