Biomimetic calcium phosphate coatings as bone morphogenetic protein delivery systems in spinal fusion.
BACKGROUND
Use of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to enhance spinal fusion rates. Case reports of soft-tissue swelling, ectopic bone formation, and osteolysis have recently surfaced. It is hypothesized that incorporation of rhBMP-2 within a calcium phosphate (CaP) coating may help to localize delivery and mitigate these complications.


OBJECTIVE
To compare the characteristics of posterolateral fusion between rabbits receiving rhBMP-2 delivered via physical adsorption to a collagen sponge or rhBMP-2 incorporated within the physical structure of a CaP coating on a collagen sponge.


METHODS
New Zealand white rabbit model of posterolateral lumbar fusion at L5-L6.


METHODS
Eighteen (18) New Zealand white rabbits underwent posterolateral spinal fusion at L5-L6. Rabbits received bilateral collagen sponges that were either coated with CaP (n=3), coated with CaP and dipped in rhBMP-2 (n=3), coated with a hybrid CaP-rhBMP-2 film (n=6), or coated with a hybrid CaP-rhBMP-2 film and dipped in rhBMP-2 (n=6). Animals were followed weekly with radiographs and were sacrificed at 6 weeks. Fusion masses were further characterized by manual palpation, computed tomography, and histology.


RESULTS
Radiographic evaluation showed that animals in Group 3 (incorporated BMP) fused at 4 weeks, whereas animals in Group 2 (adsorbed BMP) and Group 4 (incorporated and adsorbed BMP) fused by 6 weeks. Animals that received rhBMP-2 physically adsorbed to the collagen sponge showed extension of the fusion mass beyond the L5-L6 level in 56% of cases and bone resorption in 78%. Histology of fusion masses showed mature bone formation in animals belonging to Groups 2, 3, and 4 and extensive osteoclast recruitment in animals belonging to Groups 2 and 4.


CONCLUSIONS
Delivery of rhBMP-2 via incorporation within CaP coatings results in increased rates of radiographic fusion. The burst release profile of rhBMP-2 adsorbed to surfaces, although effective in achieving fusion, may result in increased osteoclast recruitment.
Majid
Kamran
K
Department of Orthopaedic Surgery, William Beaumont Hospital, Royal Oak, MI 48073, USA.
Tseng
Michael D
MD
Baker
Kevin C
KC
Reyes-Trocchia
Alma
A
Herkowitz
Harry N
HN
D000818:Animals; D040761:Biomimetic Materials / Q000627:therapeutic use*; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D002130:Calcium Phosphates / Q000008:administration & dosage*; D020099:Coated Materials, Biocompatible / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage; D013123:Spinal Fusion / Q000379:methods*; D015503:Surgical Sponges; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*
D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D020099:Coated Materials, Biocompatible; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; C020243:calcium phosphate