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Biotherapeutics in Orthopaedic Medicine

Accelerating the Healing Process?

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Abstract

Musculoskeletal injuries have a significant human and financial impact on society. In particular, fractures that lead to delayed union or even nonunion represent a serious clinical challenge for which few treatment options are available. The multiple surgical procedures often needed are associated with patient morbidity and reduced quality of life. Biotechnological advances have made possible a host of potential treatments for enhancing and accelerating the repair of bone. By stimulating the body’s own healing mechanisms, clinical outcomes may be improved while also containing procedural costs. Biotherapeutics may take the form of proteins, genes or cells that can be used to treat the injury. Protein biotherapeutics have received the greatest attention. Using recombinant DNA techniques, growth factors that play important roles in bone development and repair are being produced. By delivering exogenous growth factors to the site of injury in an appropriate manner, bone formation can be stimulated. Although individual proteins have been the primary focus of investigation, combinations of biomolecules can have additive, and perhaps synergistic, effects. Alternatively, genes coding for osteotropic growth factors can be delivered to the site of injury. Expression of the gene effectively results in localised delivery of the growth factor. Delivery of cells having osteogenic potential can also result in bone formation. Furthermore, it may be possible to obtain additional benefits by combining biotherapeutic approaches, such as by introducing cells genetically modified to overexpress therapeutic proteins of interest. Although biotherapeutics have great potential for stimulating bone repair, only a limited number of treatments have been approved by governmental regulatory agencies for clinical use. Bone morphogenetic activity was initially described in 1965, but not until 2001 and 2002 did two protein biotherapeutics, utilising bone morphogenetic proteins 2 and 7, receive approval for commercial distribution. Gene-and cell-based therapies are in a comparatively early stage of development.

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Acknowledgments

The author gratefully acknowledges the support of the Whitaker Foundation, Kentucky Science and Engineering Foundation (KSEF-148-502-03-67), and the National Institutes of Health (AR048700). The author has no conflicts of interest that are directly relevant to the content of this review.

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  1. Wenner-Gren Lab, Center for Biomedical Engineering, University of Kentucky, Lexington, KY, 40506-0070, USA

    David A. Puleo

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Puleo, D.A. Biotherapeutics in Orthopaedic Medicine. BioDrugs 17, 301–314 (2003). https://doi.org/10.2165/00063030-200317050-00001

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