title: Three-dimensional printing of rhBMP-2-loaded scaffolds with long-term delivery for enhanced bone regeneration in a rabbit diaphyseal defect.
abstract: In this study, recombinant human bone morphogenetic protein-2 (rhBMP-2) delivery system with slow mode was successfully developed in three-dimensional (3D) printing-based polycaprolactone (PCL)/poly(lactic-co-glycolic acid) (PLGA) scaffolds for bone formation of critical-sized rabbit segmental diaphyseal defect. To control the delivery of the rhBMP-2, collagen (for long-term delivery up to 28 days) and gelatin (for shor-term delivery within a week) solutions encapsulating rhBMP-2 were dispensed into a hollow cylinderical type of PCL/PLGA scaffold. An effective dose of 5μg/mL was determined by measuring the alkaline phosphatase and osteocalcin gene expression levels of human nasal inferior turbinate-derived mesenchymal stromal cells (hTMSCs) seeded on the PCL/PLGA/collagen scaffold in vitro. However, it was found that a burst release of rhBMP-2 from the PCL/PLGA/gelatin scaffold did not induce the osteogenic differentiation of hTMSCs in vitro at an equivalent dose. In the in vivo animal experiements, microcomputed tomography and histological analyses confirmed that PCL/PLGA/collagen/rhBMP-2 scaffolds (long-term delivery mode) showed the best bone healing quality at both weeks 4 and 8 after implantation without inflammatory response. On the other hand, a large number of macrophages indicating severe inflammation provoked by burst release of rhBMP-2 were observed in the vicinity of PCL/PLGA/gelatin/rhBMP-2 (short-term delivery mode) at week 4.
authors: 1 Department of Mechanical Engineering, Korea Polytechnic University , Siheung, South Korea .
authors: Jin-Hyung
authors: JH
authors: Shim
authors: Se Eun
authors: SE
authors: Kim
authors: Ju Young
authors: JY
authors: Park
authors: Joydip
authors: J
authors: Kundu
authors: Sung Won
authors: SW
authors: Kim
authors: Seong Soo
authors: SS
authors: Kang
authors: Dong-Woo
authors: DW
authors: Cho
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D018483:Diaphyses / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D005780:Gelatin / Q000494:pharmacology; D006801:Humans; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D011091:Polyesters / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D066330:Printing, Three-Dimensional; D011817:Rabbits; D011884:Radius / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D054457:Tissue Scaffolds / Q000737:chemistry*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D055114:X-Ray Microtomography
chemical_list: D055396:Bone Morphogenetic Protein 2; D011091:Polyesters; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C016240:polycaprolactone; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005780:Gelatin; D003094:Collagen