title: Local induction of inflammation affects bone formation.
abstract: To explore the influence of inflammatory processes on bone formation, we applied a new in vivo screening model. Confined biological pockets were first created in rabbits as a response to implanted bone cement discs. These biomembrane pockets were subsequently used to study the effects of inflammatory stimuli on ectopic bone formation within biphasic calcium phosphate (BCP) constructs loaded with TNF-α, lipopolysaccharide (LPS) or lipoteichoic acid (LTA), all with or without bone morphogenetic protein (BMP)-2. Analysis of bone formation after 12 weeks demonstrated that the inflammatory mediators were not bone-inductive in combination with the BCP alone, but inhibited or enhanced BMP-induced bone formation. LPS was associated with a strong inhibition of bone formation by BMP-2, while LTA and TNF-α showed a positive interaction with BMP-2. Since the biomembrane pockets did not interfere with bone formation and prevented the leakage of pro-inflammatory compounds to the surrounding tissue, the biomembrane model can be used for in vivo approaches to study local inflammation in conjunction with new bone formation. Using this model, it was shown that the modulation of the inflammatory response could be beneficial or detrimental to the subsequent bone formation process. The co-delivery of inflammatory factors and bone-related growth factors should be further explored as a strategy to enhance the bone-forming efficacy of bone substitutes.
authors.forename: M
authors.initials: M
authors.lastname: Croes
authors.forename: M C
authors.initials: MC
authors.lastname: Kruyt
authors.forename: L
authors.initials: L
authors.lastname: Loozen
authors.forename: A H
authors.initials: AH
authors.lastname: Kragten
authors.forename: H
authors.initials: H
authors.lastname: Yuan
authors.forename: W J
authors.initials: WJ
authors.lastname: Dhert
authors.forename: F C
authors.initials: FC
authors.lastname: Öner
authors.affiliation: Department of Orthopaedics, University Medical Centre Utrecht, Rm G05.228, P.O. Box 85500, Utrecht 3508 GA, The Netherlands.j.alblas@umcutrecht.nl.
authors.forename: J
authors.initials: J
authors.lastname: Alblas
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D002130:Calcium Phosphates / Q000494:pharmacology; D002449:Cell Aggregation / Q000187:drug effects; D005456:Fluorescent Dyes / Q000378:metabolism; D020007:Implants, Experimental; D007249:Inflammation / Q000473:pathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010012:Osteogenesis / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D040521:Subcutaneous Tissue / Q000187:drug effects / Q000473:pathology
chemical_list: D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D005456:Fluorescent Dyes; D008070:Lipopolysaccharides; C020243:calcium phosphate