title: Surface-modified functionalized polycaprolactone scaffolds for bone repair: in vitro and in vivo experiments.
abstract: A porcine calvaria defect study was carried out to investigate the bone repair potential of three-dimensional (3D)-printed poly-ε-caprolactone (PCL) scaffolds embedded with nanoporous PCL. A microscopic grid network was created by rapid prototyping making a 3D-fused deposition model (FDM-PCL). Afterward, the FDM-PCL scaffolds were infused with a mixture of PCL, water, and 1,4-dioxane and underwent a thermal-induced phase separation (TIPS) followed by lyophilization. The TIPS process lead to a nanoporous structure shielded by the printed microstructure (NSP-PCL). Sixteen Landrace pigs were divided into two groups with 8 and 12 weeks follow-up, respectively. A total of six nonpenetrating holes were drilled in the calvaria of each animal. The size of the cylindrical defects was h 10 mm and Ø 10 mm. The defects were distributed randomly using following groups: (a) NSP-PCL scaffold, (b) FDM-PCL scaffold, (c) autograft, (d) empty defect, (a1) NSP-PCL scaffold + autologous mononuclear cells, and (a2) NSP-PCL scaffold + bone morphogenetic protein 2. Bone volume to total volume was analyzed using microcomputed tomography (µCT) and histomorphometry. The µCT and histological data showed significantly less bone formation in the NSP-PCL scaffolds in all three variations after both 8 and 12 weeks compared to all other groups. The positive autograft control had significantly higher new bone formation compared to all other groups except the FDM-PCL when analyzed using histomorphometry. The NSP-PCL scaffolds were heavily infiltrated with foreign body giant cells suggesting an inflammatory response and perhaps active resorption of the scaffold material. The unmodified FDM-PCL scaffold showed good osteoconductivity and osseointegration after both 8 and 12 weeks.
authors.affiliation: Orthopaedic Research Laboratory, Aarhus University Hospital, DK-8000, Aarhus, Denmark.
authors.forename: Jonas
authors.initials: J
authors.lastname: Jensen
authors.forename: Jan Hendrik Duedal
authors.initials: JH
authors.lastname: Rölfing
authors.forename: Dang Quang Svend
authors.initials: DQ
authors.lastname: Le
authors.forename: Asger Albaek
authors.initials: AA
authors.lastname: Kristiansen
authors.forename: Jens Vinge
authors.initials: JV
authors.lastname: Nygaard
authors.forename: Lea Bjerre
authors.initials: LB
authors.lastname: Hokland
authors.forename: Michael
authors.initials: M
authors.lastname: Bendtsen
authors.forename: Moustapha
authors.initials: M
authors.lastname: Kassem
authors.forename: Helle
authors.initials: H
authors.lastname: Lysdahl
authors.forename: Cody Eric
authors.initials: CE
authors.lastname: Bünger
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000494:pharmacology; D001861:Bone Regeneration / Q000187:drug effects*; D002460:Cell Line; D005260:Female; D006801:Humans; D010012:Osteogenesis / Q000187:drug effects; D011091:Polyesters / Q000737:chemistry*; D012886:Skull / Q000187:drug effects / Q000293:injuries / Q000502:physiology* / Q000648:ultrastructure; D013499:Surface Properties; D013552:Swine; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D055396:Bone Morphogenetic Protein 2; D011091:Polyesters; C016240:polycaprolactone
keywords: biodegradation; bone tissue engineering; foreign body giant cell; poly-ε-caprolactone; scaffold