Session V - Fracture Healing

Friday, October 13, 2000 Session V, Paper #33, 9:28 am

Bioactive Implants with Incorporated IGF-I and TGF-beta 1 Accelerate Fracture Healing

Gerhard Schmidmaier, MD; Britt Wildemann, PhD; Martin Lucke, MD; Herman Bail, MD; Michael Raschke, MD, Humboldt University of Berlin, Berlin, Germany

Purpose: Bioactive implants could accelerate bone metabolism and reduce local and systemic problems in fracture treatment and joint replacement. Former studies investigated the properties of a new Poly (D,L-lactide) (PDLLA) coating on metallic implants for the local application of drugs. The coating demonstrated a high mechanical stability during intramedullary insertion. The incorporated growth factors showed a continuous release of 80% within 6 weeks after an initial peak. In histomorphometric and biomechanical studies in rats, we found a significant acceleration of fracture healing by locally released rh-IGF-I and rh-TGF-ß1. The purpose of this study was the evaluation of this bioactive coating of implants in a large animal model.

Methods: Titanium tibia nails were coated with a biodegradable thin layer (10 µm) of PDLLA with incorporated rh-IGF-I (5% of total coating mass) and rh-TGF-ß1 (1%). A standardized osteotomy (1-mm gap) of the right tibia in 30 Yucatan micro-pigs (mean body weight 35 kg) was performed. The tibiae were intramedullary stabilized with coated versus uncoated titanium nails (diameter 0.5 cm) and statically interlocked. The following groups were examined:

Group I implants uncoated (n=10)

Group II implants with PDLLA coating (n=10)

Group III implants coated with PDLLA + rh-IGF-I (5%) and

rh-TGF-ß1 (1%) (n=10)

After osteotomy and intramedullary stabilization, radiographic examinations (posteroanterior and lateral) were performed, and serum samples, including IGF-I and TGF-ß1, were taken. Body weight and temperature were determined at 0 days, 4 days, 7 days, 14 days, 21 days and 28 days. The animals were sacrificed after 4 weeks. Both tibiae were dissected for biomechanical torsional testing. The diameter of the calluses was determined (posteroanterior and lateral) with a Vernier caliper and the callus volume measured using the Archimedic principle.

Results: After 4 weeks the radiographic examinations of the control group showed incomplete consolidation of the osteotomy. In all animals of group I, the osteotomy gap could still be recognized after 4 weeks. In group II (PDLLA coating), we found good callus formation in comparison to the uncoatd group I. The animals of group III (PDLLA + rh-IGF-I + rh-TGF-ß1) demonstrated progressed callus formation as observed by radiography and significantly (P <0.05) larger callus diameter and higher volume versus group II and group I. Compared to the non-osteotomized tibiae we found significantly higher torsional stiffness and maximum load of the PDLLA + rh-IGF-I + rh-TGF-ß1 coated group III versus the PDLLA coated group II and the uncoated group I.

The uncoated group I demonstrated less torsional stability than the PDLLA coated group I (not significant). We did not found any systemic change of electrolytes, thyroid hormone levels or systemic IGF-I and TGF-ß1 between all groups. No change in body weight or body temperature was observed.

Discussion & Conclusion: The results demonstrate that biologically active implants, coated with PDLLA and incorporated growth factors, (rh-IGF-I and rh-TGF-ß1) significantly accelerate bone healing. The PDLLA coating alone is already characterized by a high mechanical stability on metallic implants and a positive effect on bone healing, without any additional drugs. Therefore PDLLA seems to be an ideal carrier for the local application of growth factors from coated biomaterials.

The combined application of IGF-I and TFG-ß1 from a biodegradable PDLLA coating of implants accelerated bone healing in Yucatan micro-pigs without systemic side effects.