title: Endochondral bone formation in gelatin methacrylamide hydrogel with embedded cartilage-derived matrix particles.
abstract: The natural process of endochondral bone formation in the growing skeletal system is increasingly inspiring the field of bone tissue engineering. However, in order to create relevant-size bone grafts, a cell carrier is required that ensures a high diffusion rate and facilitates matrix formation, balanced by its degradation. Therefore, we set out to engineer endochondral bone in gelatin methacrylamide (GelMA) hydrogels with embedded multipotent stromal cells (MSCs) and cartilage-derived matrix (CDM) particles. CDM particles were found to stimulate the formation of a cartilage template by MSCs in the GelMA hydrogel in vitro. In a subcutaneous rat model, this template was subsequently remodeled into mineralized bone tissue, including bone-marrow cavities. The GelMA was almost fully degraded during this process. There was no significant difference in the degree of calcification in GelMA with or without CDM particles: 42.5 ± 2.5% vs. 39.5 ± 8.3% (mean ± standard deviation), respectively. Interestingly, in an osteochondral setting, the presence of chondrocytes in one half of the constructs fully impeded bone formation in the other half by MSCs. This work offers a new avenue for the engineering of relevant-size bone grafts, by the formation of endochondral bone within a degradable hydrogel.
authors.affiliation: Department of Orthopaedics, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands.
authors.forename: Jetze
authors.initials: J
authors.lastname: Visser
authors.affiliation: Department of Orthopaedics, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands; Department of Oral and Maxillofacial Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands.
authors.forename: Debby
authors.initials: D
authors.lastname: Gawlitta
authors.affiliation: Department of Orthopaedics, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands.
authors.forename: Kim E M
authors.initials: KE
authors.lastname: Benders
authors.affiliation: Department of Orthopaedics, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands.
authors.forename: Selynda M H
authors.initials: SM
authors.lastname: Toma
authors.affiliation: Department of Orthopaedics, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands; Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, 2628 CD Delft, The Netherlands.
authors.forename: Behdad
authors.initials: B
authors.lastname: Pouran
authors.affiliation: Department of Equine Sciences, Faculty of Veterinary Sciences, Utrecht University, Yalelaan 112, 3584 CM Utrecht, The Netherlands.
authors.forename: P René
authors.initials: PR
authors.lastname: van Weeren
authors.affiliation: Department of Orthopaedics, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands; Department of Equine Sciences, Faculty of Veterinary Sciences, Utrecht University, Yalelaan 112, 3584 CM Utrecht, The Netherlands.
authors.forename: Wouter J A
authors.initials: WJ
authors.lastname: Dhert
authors.affiliation: Department of Orthopaedics, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands; Department of Equine Sciences, Faculty of Veterinary Sciences, Utrecht University, Yalelaan 112, 3584 CM Utrecht, The Netherlands. Electronic address: j.malda@umcutrecht.nl.
authors.forename: Jos
authors.initials: J
authors.lastname: Malda
mesh_terms: D000178:Acrylamides / Q000494:pharmacology*; D000818:Animals; D002356:Cartilage / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005780:Gelatin / Q000494:pharmacology*; D006736:Horses; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D011923:Rats, Nude; D034421:Sus scrofa; D055114:X-Ray Microtomography
chemical_list: D000178:Acrylamides; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005780:Gelatin; C045985:methacrylamide
keywords: Decellularized matrix; GelMA; Rat; Regeneration; Tissue engineering