Variation in Calvarial Bone Healing Capacity

Abstract

Bone morphogenetic protein-2 (BMP-2) together with a suitable carrier is an attractive option that may be used for craniofacial bone reconstruction. In this prospective randomized study, a hyaluronan-based hydrogel with BMP-2 was used to achieve bone healing in standardized critical-size cranial defects in humans after neurosurgery. Twelve patients were randomized into the treatment group (N = 6) or control group (N = 6). In the treatment group, holes made during craniotomy were treated with hydrogel with BMP-2, 250 µg/mL, or hydrogel without BMP-2. In the remaining hole/s in the same patient, Spongostan (Ethicon) alone or Tisseel (Baxter) mixed with autologous bone matrix were used as negative and positive controls, respectively. In the control group, the holes were treated with Spongostan or Tisseel mixed with bone autograft. Bone healing was assessed with CT scans after 3 and 6 months. Bone areas in treated defects were measured and statistical analysis was performed. Independent of location, bone healing in defects treated with Tisseel with autograft, hydrogel alone, or hydrogel with BMP-2 was significantly increased compared to negative control (P < 0.001, P = 0.002, and P = 0.005, respectively). In general, all defects healed significantly better in the frontal bone as compared to parietal-temporal location, except for defects treated with Tisseel and autograft, which healed well independently of location. No local or systemic side effects, including excessive bone overgrowth or inflammatory reaction, were seen in treated patients. Tissue engineering of bone with hyaluronan-based hydrogel shows good healing of cranial defects, comparable with bone autografts. The hydrogel itself may represent a novel alternative to autologous bone transplants in craniofacial bone repair. The study also reveals a general superior healing capacity in the frontal bone as compared to parietal/temporal bones.