Telopeptide‐depleted bovine skin collagen as a carrier for bone morphogenetic protein

Abstract

The telopeptide of type I collagen is thought to be responsible for causing immunogenic response when introduced into xenogenic hosts. To eliminate this problem, solubilized bovine skin collagen was filtered through a millipore membrane, digested repeatedly with pepsin to remove telopeptides, and used as a carrier for a water-soluble, partially-purified fraction of bone morphogenetic protein (BMP) in mice. Composite implants of this telopeptide-depleted collagen and the partially-purified BMP fraction consistently elicited ectopic bone formation in mice 3 weeks postimplantation. When implanted alone, collagen or BMP failed to show this response. Collagens, prepared by use of conventional methods (acid-solubilized collagen, or collagen-digested once with pepsin) were also assessed as carriers for BMP, but were found to be inferior in terms of consistency of bone formation and amount of induced bone mass. The results suggest that telopeptide-depleted collagen permitted a gradual release of purified BMP for induction of bone, with minimal immunogenic interference. Consequently, this collagen carrier represents an important development for future clinical application of BMP.

Synthetic biodegradable polymers as drug delivery systems for bone morphogenetic proteins

“…Osteoconductive delivery systems have included collagenous materials, such as type I collagen (as sponges, gels, or fibrils) [19,[26][27][28][29][30], and type IV collagen [31,32]; inorganic ceramic materials, such as hydroxyapatite (HA) (as a powder, granules, or blocks) [33,34], tricalcium phosphate (TCP) [35], glass ceramic, and other inorganic materials; cartilage-or bone-derived materials, such as coral, chitin, and bone mineral,; and composites of different types of these materials [20]. BMP have also been used in combination with titanium and other metal alloys [36].…”

Stimulation of Ectopic Bone Formation in Response to BMP-2 by Rho Kinase Inhibitor: A Pilot Study

“…To explore the mechanism for BMP-induced bone formation, we developed an in vivo experimental model system for the local delivery of recombinant human BMP-2 (rhBMP-2) impregnated in pepsin-digested Type I collagen [29]. With this model we can reproducibly induce ectopic bone and assess bone formation quantitatively in any wildtype or transgenic mice [17,34].…”

Long-Term Observation of Ectopic Bone Formation Using In Vivo Microcomputed Tomography

“…Bone morphogenetic protein1-3), which is a bioactive factor, has been traditionally used to induce bone reconstruction in conjunction with various biomaterials [4][5][6][7] .…”