Recommendations and considerations for the use of biologics in orthopedic surgery

Abstract

Reconstruction of extensive bone defects remains technically challenging and has considerable medical and financial impact on our society. Surgical procedures often require a bone/substitute graft to enhance and accelerate bone repair. Bone autografts are associated with morbidity related to bone harvesting and are limited in quantity. Alternatively, bone allografts expose the patient to the risk of transmission of infectious disease. Synthetic bone graft substitutes, such as calcium sulfates, hydroxyapatite, tricalcium phosphate, and combinations, circumvent some of the disadvantages of auto- and allografts, but have limited indications. Biomedical research has made possible the stimulation of the body's own healing mechanisms, either by delivering exogenous growth factors locally, or by stimulating their local production by gene transfer. Among all known factors having osteoinductive properties, only two bone morphogenetic proteins (for specific indications) and demineralized bone matrix have been approved for clinical use. In addition, ongoing research is exploring the efficacy of cell therapy and tissue engineering. The present report examines the composition, biological properties, indications, clinical experience and regulations of several of the biotherapeutics employed for bone reconstruction.

Fig. 1

Biologics in orthopedic surgery. The field of orthopedic surgery is currently using and investigating many different biologics with an aim of improving cell and tissue regeneration. The current gold standard is the bone autograft. Additional agents presented here are osteoconductive scaffolds, growth factors, cells, combination products, hormone therapy, and gene therapy. The current status of each product, whether it is used in basic science investigations, undergoing clinical trials, or US FDA approved for clinical usage, is denoted by red, blue, and green, respectively. BMP = bone morphogenetic protein; CPCs = calcium phosphate ceramics; DBM = demineralized bone matrix; MSCs = mesenchymal stromal cells; PRP = platelet-rich plasma.