title: Decellularized cartilage-derived matrix as substrate for endochondral bone regeneration.
abstract: Following an endochondral approach to bone regeneration, multipotent stromal cells (MSCs) can be cultured on a scaffold to create a cartilaginous callus that is subsequently remodeled into bone. An attractive scaffold material for cartilage regeneration that has recently regained attention is decellularized cartilage-derived matrix (CDM). Since this material has shown potential for cartilage regeneration, we hypothesized that CDM could be a potent material for endochondral bone regeneration. In addition, since decellularized matrices are known to harbor bioactive cues for tissue formation, we evaluated the need for seeded MSCs in CDM scaffolds. In this study, ectopic bone formation in rats was evaluated for CDM scaffolds seeded with human MSCs and compared with unseeded controls. The MSC-seeded samples were preconditioned in chondrogenic medium for 37 days. After 8 weeks of subcutaneous implantation, the extent of mineralization was significantly higher in the MSC-seeded constructs versus unseeded controls. The mineralized areas corresponded to bone formation with bone marrow cavities. In addition, rat-specific bone formation was confirmed by collagen type I immunohistochemistry. Finally, fluorochrome incorporation at 3 and 6 weeks revealed that the bone formation had an inwardly directed progression. Taken together, our results show that decellularized CDM is a promising biomaterial for endochondral bone regeneration when combined with MSCs at ectopic locations. Modification of current decellularization protocols may lead to enhanced functionality of CDM scaffolds, potentially offering the prospect of generation of cell-free off-the-shelf bone regenerative substitutes.
authors.affiliation: 1 Department of Orthopedics, University Medical Center Utrecht , Utrecht, The Netherlands .
authors.forename: Debby
authors.initials: D
authors.lastname: Gawlitta
authors.forename: Kim E M
authors.initials: KE
authors.lastname: Benders
authors.forename: Jetze
authors.initials: J
authors.lastname: Visser
authors.forename: Anja S
authors.initials: AS
authors.lastname: van der Sar
authors.forename: Diederik H R
authors.initials: DH
authors.lastname: Kempen
authors.forename: Lars F H
authors.initials: LF
authors.lastname: Theyse
authors.forename: Jos
authors.initials: J
authors.lastname: Malda
authors.forename: Wouter J A
authors.initials: WJ
authors.lastname: Dhert
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis; D001861:Bone Regeneration / Q000502:physiology*; D018786:Bone Substitutes / Q000138:chemical synthesis / Q000737:chemistry; D002358:Cartilage, Articular / Q000737:chemistry*; D002474:Cell-Free System; D002478:Cells, Cultured; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005109:Extracellular Matrix / Q000737:chemistry*; D006801:Humans; D008297:Male; D008422:Materials Testing; D045164:Mesenchymal Stem Cell Transplantation / Q000295:instrumentation*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D051381:Rats; D011923:Rats, Nude; D023822:Tissue Engineering / Q000295:instrumentation; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D018786:Bone Substitutes