Enhanced bone regeneration at a segmental bone defect by controlled release of bone morphogenetic protein-2 from a biodegradable hydrogel.

The objective of this study is to investigate the feasibility of a biodegradable hydrogel of gelatin as the controlled release carrier of bone morphogenetic protein-2 (BMP-2) suitable for enhancement of bone regeneration at a segmental bone defect. Hydrogels with three different water contents were prepared through glutaraldehyde crosslinking of gelatin with an isoelectric point of 9.0 under varied reaction conditions. Segmental critical-sized defects (20 mm) were created at the ulnar bone of skeletally mature New Zealand white rabbits, and gelatin hydrogels incorporating BMP-2 (17 microg/hydrogel) were implanted into the defects. When bone regeneration was evaluated by soft x-ray observation and bone mineral density (BMD) measurement, the gelatin hydrogels incorporating BMP- 2 exhibited significantly high osteoinduction activity compared with that of free BMP-2, although the activity depended on the water content of the hydrogels. Significantly higher BMD enhancement was observed in the gelatin hydrogel with a water content of 97.8 wt% than that with the lower or higher water content. We concluded that the biodegradable gelatin hydrogel is a promising controlled release carrier of BMP-2 for bone regeneration at the segmental bone defect.

[1]  E. Jabbari,et al.  Gelation and degradation characteristics of in situ photo-crosslinked poly(l-lactide-co-ethylene oxide-co-fumarate) hydrogels , 2007 .

[2]  K. Kraus,et al.  Use of bone morphogenetic proteins for augmentation of bone regeneration. , 2007, Journal of the American Veterinary Medical Association.

[3]  Y. Tabata,et al.  Cationized catalase-loaded hydrogel for growth inhibition of peritoneally disseminated tumor cells. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[4]  A. Hokugo A Novel Functional Scaffold Combined With Bone Marrow Cells to Enhance Bone Regeneration After Radiation Therapy: An Experimental Study in Rabbits , 2007 .

[5]  S. Yuk,et al.  Polymeric protein delivery systems , 2007 .

[6]  Y. Tabata,et al.  Controlled release of platelet growth factors enhances bone regeneration at rabbit calvaria. , 2007, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[7]  Heungsoo Shin,et al.  Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage tissue engineering. , 2007, Advanced drug delivery reviews.

[8]  Matthew Pilarz,et al.  Controlling hydrogelation kinetics by peptide design for three-dimensional encapsulation and injectable delivery of cells , 2007, Proceedings of the National Academy of Sciences.

[9]  Y. Tabata,et al.  Skull bone regeneration in nonhuman primates by controlled release of bone morphogenetic protein-2 from a biodegradable hydrogel. , 2007, Tissue engineering.

[10]  T. Einhorn,et al.  Use of bone morphogenetic proteins for musculoskeletal applications. An overview. , 2004, The Journal of bone and joint surgery. American volume.

[11]  D. Ring,et al.  Operative Release of Ankylosis of the Elbow Due to Heterotopic Ossification , 2004 .

[12]  W. Friess,et al.  Collagen sponges for bone regeneration with rhBMP-2. , 2003, Advanced drug delivery reviews.

[13]  Y. Tabata,et al.  Controlled release by biodegradable hydrogels enhances the ectopic bone formation of bone morphogenetic protein. , 2003, Biomaterials.

[14]  Jay R Lieberman,et al.  The role of growth factors in the repair of bone. Biology and clinical applications. , 2002, The Journal of bone and joint surgery. American volume.

[15]  Kazutoshi Nozaki,et al.  A biodegradable polymer as a cytokine delivery system for inducing bone formation , 2001, Nature Biotechnology.

[16]  Y. Tabata,et al.  Controlled Release of Hepatocyte Growth Factor from Gelatin Hydrogels Based on Hydrogel Degradation , 2001, Journal of drug targeting.

[17]  H. Uludaǧ,et al.  Growth Factor Delivery for Bone Tissue Engineering , 2001, Journal of drug targeting.

[18]  Y. Ikada,et al.  Bone regeneration by transforming growth factor beta1 released from a biodegradable hydrogel. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[19]  J. Wozney,et al.  Recombinant human bone morphogenetic protein-2 and collagen for bone regeneration. , 1998, Journal of biomedical materials research.

[20]  D. Chamberland,et al.  Radiomorphometry and biomechanical assessment of recombinant human bone morphogenetic protein 2 and polymer in rabbit radius ostectomy model. , 1998, Journal of biomedical materials research.

[21]  Hollinger,et al.  Sustained release emphasizing recombinant human bone morphogenetic protein-2. , 1998, Advanced drug delivery reviews.

[22]  J. Wozney,et al.  Bone Formation with Use of rhBMP-2 (Recombinant Human Bone Morphogenetic Protein-2)* , 1997, The Journal of bone and joint surgery. American volume.

[23]  Y. Ikada,et al.  Enhanced vascularization and tissue granulation by basic fibroblast growth factor impregnated in gelatin hydrogels , 1994 .

[24]  E. Dawson,et al.  Beta-tricalcium phosphate delivery system for bone morphogenetic protein. , 1984, Clinical orthopaedics and related research.

[25]  V. Rosen,et al.  Bone morphogenetic protein and bone morphogenetic protein gene family in bone formation and repair. , 1998, Clinical orthopaedics and related research.

[26]  D. Zekorn Intravascular retention, dispersal, excretion and break-down of gelatin plasma substitutes. , 1969, Bibliotheca haematologica.