title: Complete subchondral bone defect regeneration with a tricalcium phosphate collagen implant and osteoinductive growth factors: a randomized controlled study in Göttingen minipigs.
abstract: The restoration and reconstruction of osseous defects close to the joint, constitutes a challenging field for reconstructive surgery. A dual-layer implant of β-tricalcium phosphate (TCP) and a collagens I/III scaffold was evaluated in a prospective, randomized comparison in a larger animal model. For this purpose, a standardized osteochondral defect was created in the medial facet of the patellar groove in both stifle joints of Göttingen minipigs. Critical-size osseous defects were either left empty (spontaneous healing; group 1; n = 12) or treated with the two-layer TCP collagen implant (group 2; n = 12). In group 3 (n = 12), additional growth factor mixture (GFM) was supplemented (bone morphogenetic proteins 2, 3, 4, 6, 7, and TGF-β1, 2, 3). Osseous defect regeneration was assessed at 6, 12, and 52 weeks postoperatively (n = 4). Qualitative and quantitative histomorphometric assessment of defect regeneration and bone substitute resorption was conducted by means of light microscopy, fluorescence microscopy, and microradiography. Critical-size defects did not heal spontaneously throughout follow-up (group 1: max. 21.84 ± 2.81% defect area at 52 weeks). The TCP layer of the implant significantly increased the amount of new bone formation with 29.8 ± 9.68% at 6 weeks and 40.09 ± 4.76% at 12 weeks when compared with controls. After 52 weeks, the TCP was almost fully degraded (4.35 ± 3.70%) and the defect was restored with lamellar trabecular bone (31.28 ± 5.02%). Growth factor supplementation resulted in earlier resorption of the TCP implant and faster defect regeneration. The dual-layer TCP collagen implant is suitable to restore subchondral osseous defects. Additional use of GFM increased the resorption of the TCP layer, but did not foster new bone formation.
authors.affiliation: Clinic of Orthopaedic and Trauma Surgery, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Gotterbarm
authors.forename: Steffen J
authors.initials: SJ
authors.lastname: Breusch
authors.forename: Martin
authors.initials: M
authors.lastname: Jung
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Streich
authors.forename: Jörg
authors.initials: J
authors.lastname: Wiltfang
authors.forename: Simona
authors.initials: S
authors.lastname: Berardi Vilei
authors.forename: Wiltrud
authors.initials: W
authors.lastname: Richter
authors.forename: Tobias
authors.initials: T
authors.lastname: Nitsche
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000737:chemistry / Q000494:pharmacology; D001861:Bone Regeneration / Q000187:drug effects*; D018786:Bone Substitutes / Q000737:chemistry / Q000494:pharmacology; D001842:Bone and Bones / Q000293:injuries* / Q000473:pathology; D002130:Calcium Phosphates / Q000737:chemistry / Q000494:pharmacology; D003094:Collagen / Q000737:chemistry / Q000494:pharmacology; D013552:Swine; D013556:Swine, Miniature; D054457:Tissue Scaffolds
chemical_list: D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D002130:Calcium Phosphates; D003094:Collagen; C018392:tricalcium phosphate
keywords: bilayered construct; growth factors; osteochondral defect; subchondral bone repair; β-TCP