Functional bone engineering using ex vivo gene therapy and topology-optimized, biodegradable polymer composite scaffolds.
Bone tissue engineering could provide an alternative to conventional treatments for fracture nonunion, spinal fusion, joint replacement, and pathological loss of bone. However, this approach will require a biocompatible matrix to allow progenitor cell delivery and support tissue invasion. The construct must also support physiological loads as it degrades to allow the regenerated tissue to bear an increasing load. To meet these complex requirements, we have employed topology-optimized design and solid free-form fabrication to manufacture biodegradable poly(propylene fumarate)/beta-tricalcium phosphate composites. These scaffolds were seeded with primary human fibroblasts transduced with an adenovirus expressing bone morphogenetic protein-7 and implanted subcutaneously in mice. Specimens were evaluated by microcomputed tomography, compressive testing, and histological staining. New bone was localized on the scaffold surface and closely followed its designed contours. Furthermore, the total stiffness of the constructs was retained for up to 12 weeks after implantation, as scaffold degradation and tissue invasion took place.
Lin
Chia-Ying
CY
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA.
Schek
Rachel M
RM
Mistry
Amit S
AS
Shi
Xinfeng
X
Mikos
Antonios G
AG
Krebsbach
Paul H
PH
Hollister
Scott J
SJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry; D001673:Biodegradation, Environmental; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D001861:Bone Regeneration; D001842:Bone and Bones / Q000166:cytology / Q000502:physiology*; D002130:Calcium Phosphates / Q000737:chemistry; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D019245:Compressive Strength; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000000981:diagnostic imaging / Q000378:metabolism / Q000502:physiology* / Q000637:transplantation; D005650:Fumarates / Q000737:chemistry; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D005881:Gingiva / Q000166:cytology; D006651:Histocytochemistry; D006652:Histological Techniques; D006801:Humans; D007279:Injections, Subcutaneous; D008422:Materials Testing; D051379:Mice; D011108:Polymers / Q000737:chemistry*; D011126:Polypropylenes / Q000138:chemical synthesis / Q000737:chemistry; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D014057:Tomography, X-Ray Computed; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous
C525819:BMP7 protein, human; D001672:Biocompatible Materials; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D002130:Calcium Phosphates; D005650:Fumarates; D011108:Polymers; D011126:Polypropylenes; D016212:Transforming Growth Factor beta; C485817:beta-tricalcium phosphate; C032005:fumaric acid