The successful treatment of large bony defects and infections of the bone is still a challenge in orthopedic and trauma surgery. The research and development of materials for bone grafting and local drug release increased in the last decades, the developed materials, however, are often very complex, making translation into the clinic difficult. Demineralized bone matrix (DBM) made out of allogeneic bone is a clinically well-established grafting material. An easy perioperative procedure for loading DBM with osteoinductive and antimicrobial substances can optimize the material for the treatment of challenging indications.
DBM (DIZG, Germany) was loaded with the growth factor bone morphogenetic protein-2 (BMP-2) or antibiotics by using a special mixing syringe. Release kinetics and the activity of the incorporated drugs were investigated in vitro. Using a drill hole model in sheep, osteoinductivity of the BMP-2 enriched DBM and the biocompatibility of gentamicin enriched DBM was analyzed by µCT and histology after 3 and 9 weeks (6 - 8 drill holes per group and time point).
Loading of DBM with BMP-2 revealed a burst release within the first 7 days, but also depot storage of the active growth factor over 56 days. In contrast, the antibiotics were completely release within 7 days. Elutes showed an antimicrobial activity against S. aureus over at least three days with no negative effect on osteoblast-like cells. Drill holes filled with BMP-2 enriched DBM induced a regeneration of the defects over 3 and 9 weeks with a reconstitution of the native bone structure. Enrichment with gentamicin resulted in an impaired regeneration as demonstrated by µCT and histology.
Using this mixing procedure, loading of DBM was fast, reliable and possible during surgical setting. In vitro experiments revealed differences between the incorporated growth factor -depot storage- and the antibiotics -complete burst release. BMP-2 enrichment promoted successfully bone regeneration. Although the gentamicin/DBM concentration was in the range of clinically used antibiotic-loaded-cement for prophylaxis and treatment in joint replacement (Jiranek et al. 2006) a negative effect on bone formation was seen. The delayed healing seen in vivo was unexpected due to the good biocompatibility found in vitro. Due to the fast and complete release of the antibiotic from the DBM compared to antibiotic loaded cement, the amount of antibiotic should be much lower in the DBM compared to cement.