Abstract
Bone morphogenetic proteins (BMPs) possess a unique ability to induce new bone formation. Numerous preclinical studies have been conducted to develop novel, BMP-based osteoinductive devices for the management of segmental bone defects and posterolateral spinal fusion (PLF). In these studies, BMPs were combined with a broad range of carriers (natural and synthetic polymers, inorganic materials, and their combinations) and tested in various models in mice, rats, rabbits, dogs, sheep, and non-human primates. In this review, we summarized bone regeneration strategies and animal models used for the initial, intermediate, and advanced evaluation of promising therapeutical solutions for new bone formation and repair. Moreover, in this review, we discuss basic aspects to be considered when planning animal experiments, including anatomical characteristics of the species used, appropriate BMP dosing, duration of the observation period, and sample size.
Highlights
Bone tissue possesses unique regenerative properties, and bone fractures regularly heal under physiological conditions
We demonstrated that BMP6 appears to be superior to BMP2 and BMP7 in promoting osteoblast differentiation in vitro and inducing bone formation in vivo [23,24]
Biocompatible and biodegradable synthetic polymers, such as polylactic acid (PLA), polyglycolic acid (PGA), poly(D, L-lactide-co-glycolide) (PLGA), polyethylene glycol (PEG), poly-E-caprolactone (PCL), and polypropylene fumarate (PPF), as well as their block polymers have been evaluated as potential Bone morphogenetic proteins (BMPs) carriers to overcome the disadvantages of natural polymers, including immunogenicity and disease transmission risk [39,40,41,42]
Summary
Bone tissue possesses unique regenerative properties, and bone fractures regularly heal under physiological conditions. The standard of care for the healing of large bone defects requires the use of an autologous bone graft (ABG), which is usually harvested from the iliac crest. Osteoinductive devices are under investigation for clinical use in PLF and healing of large segmental long bone defects. In the last few decades, numerous preclinical studies using animal models have been conducted to test novel bone bridging or fusion strategies [8,9]. The principles of the rational use of animal models in the evaluation of novel bone regenerative therapies have been previously described [8]. We further investigated the use of animal models in the development of osteoinductive therapies of large segmental bone defects and PLF procedures, in particular the selection of a proper anatomical model, treatment dose, observation period, and sample size. We analyzed published in vivo studies looking into the development of bone morphogenetic protein (BMP)-based bone inducing implants
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