Tissue-engineered rabbit cranial suture from autologous fibroblasts and BMP2

Abstract

Craniosynostosis is a congenital disorder of premature ossification of cranial sutures, occurring in one of approximately every 2500 live human births. This work addressed a hypothesis that a cranial suture can be tissue-engineered from autologous cells. Dermal fibroblasts were isolated subcutaneously from growing rabbits, culture-expanded, and seeded in a gelatin scaffold. We fabricated a composite tissue construct by sandwiching the fibroblast-seeded gelatin scaffold between two collagen sponges loaded with recombinant human BMP2. Surgically created, full-thickness parietal defects were filled with the composite tissue construct in the same rabbits from which dermal fibroblasts had been obtained. After four-week in vivo implantation, there was de novo formation of tissue-engineered cranial suture, microscopically reminiscent of the adjacent natural cranial suture. The tissue-engineered cranial suture showed radiolucency on radiographic images, in contrast to radio-opacity of microscopically ossified calvarial defects filled with fibroblast-free, BMP2-loaded constructs. This approach may be refined for tissue engineering of cranial sutures for craniosynostosis patients.