Osteogenic molecules for clinical applications: improving the BMP-collagen system

Rick Visser,Leonor Santos-Ruiz,Manuel Cifuentes,José Becerra,Pilar M Arrabal

doi:10.4067/s0716-97602013000400013

Abstract

Among the osteogenic growth factors used for bone tissue engineering, bone morphogenetic proteins (BMPs) are the most extensively studied for use in orthopaedic surgery. BMP-2 and BMP-7 have been widely investigated for developing therapeutic strategies and are the only two approved for use in several clinical applications. Due to the chemical and biological characteristics of these molecules, their authorised uses are always in combination with a carrier based on collagen type I. Although the use of these growth factors is considered safe in the short term, the very high doses needed to obtain significant osteoinduction make these treatments expensive and their long-term safety uncertain, since they are highly pleiotropic and have the capacity to induce ectopic ossification in the surrounding tissues. Therefore it is necessary to improve the currently used BMP-collagen system in terms of efficiency, biosecurity and costs. There are several strategies to increase the clinical effectiveness of these treatments. In this review we summarize the most promising results and our related work focused on this field through two different approaches: i) the development of recombinant BMPs with additional features, and ii) complementing these systems with other growth factors or molecules to enhance or accelerate osteogenesis.

Highlights

Healing of bone defects and fractures caused by trauma, tumour resection or disease constitutes a significant clinical and economic problem due to the limited effectiveness of the current treatment options.The expected time for a fracture to heal naturally is between six and twelve weeks, but there is a high rate of delayed unions, varying from 16-60% for less severe fractures to 43-100% for more severe cases
Among the osteogenic growth factors used for bone tissue engineering, bone morphogenetic proteins (BMPs) are the most extensively studied for use in orthopaedic surgery
In this review we summarize the most promising results and our related work focused on this field through two different approaches: i) the development of recombinant BMPs with additional features, and ii) complementing these systems with other growth factors or molecules to enhance or accelerate osteogenesis

Summary

Introduction

Healing of bone defects and fractures caused by trauma, tumour resection or disease constitutes a significant clinical and economic problem due to the limited effectiveness of the current treatment options.The expected time for a fracture to heal naturally is between six and twelve weeks, but there is a high rate of delayed unions, varying from 16-60% for less severe fractures to 43-100% for more severe cases. It has been demonstrated that new bone formation can be achieved by direct application of BMPs alone (Wozney et al, 1990; Einhorn et al, 2003), but these approaches require the use of very high doses of growth factors, since they have a short half-life in vivo and suffer rapid systemic dispersion after injection.

Results

Conclusion