title: Tissue reactions to particles of bone-substitute materials in intraosseous and heterotopic sites in rats: discrimination of osteoinduction, osteocompatibility, and inflammation.
abstract: Two rat models were used to characterize tissue-specific reactions to particles of bone-substitute materials: one for osteocompatibility in a healing tibial wound and the other in a heterotopic, subcutaneous site. Small, unicortical tibial wounds in rats healed spontaneously, beginning with the rapid proliferation of intramedullary woven bone. That temporary bone was resorbed by osteoclasts and finally, the cortical wound was healed with lamellar bone and the medullary space was repopulated with marrow. When various particulate materials were implanted into fresh wounds, three types of reactions were observed. (1) Demineralized bone powder (DBP) and non-resorbable calcium phosphate (nrCP) were incorporated into the reactive medullary and cortical bone. (2) Polymethylmetlhacrylate (PMMA) particles were surrounded with a fibrous layer, but did not impair bone healing. (3) Polyethylene (PE) shards and resorbable calcium phosphates (rCPs) were inflammatory and inhibited osseous repair. Subcutaneous sites showed osteoinductive, fibrotic, or inflammatory responses to these materials. Only DBP induced endochondral osteogenesis subcutaneously. The nrCP evoked a fibrous reaction. In contrast, rCPs, PMMA, and PE shards generated inflammatory reactions with each particle being surrounded by fibrous tissue and large multinucleated giant cells. In conclusion, only DBP showed osteoinductive as well as osteocompatible properties. The nrCP was osteocompatible. The rCPs stimulated various degrees of inflammatory responses. PMMA was osteocompatible and did not interfere with the bone healing process. PE was not osteocompatible and generated foreign body reactions in both sites. Use of the two sites distinguishes osteoinductive, osteocompatible, and inflammatory properties of particles of bone-substitute materials.
authors.affiliation: Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: K
authors.initials: K
authors.lastname: Eid
authors.forename: S
authors.initials: S
authors.lastname: Zelicof
authors.forename: B P
authors.initials: BP
authors.lastname: Perona
authors.forename: C B
authors.initials: CB
authors.lastname: Sledge
authors.forename: J
authors.initials: J
authors.lastname: Glowacki
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D001843:Bone Cements / Q000494:pharmacology; D018775:Bone Demineralization Technique; D018786:Bone Substitutes / Q000494:pharmacology*; D002130:Calcium Phosphates / Q000276:immunology / Q000494:pharmacology; D008297:Male; D008422:Materials Testing; D016348:Osseointegration / Q000276:immunology*; D009999:Ossification, Heterotopic / Q000139:chemically induced* / Q000276:immunology; D010000:Osteitis / Q000276:immunology*; D020959:Polyethylene / Q000276:immunology / Q000494:pharmacology; D019904:Polymethyl Methacrylate / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013977:Tibia / Q000293:injuries / Q000601:surgery; D014945:Wound Healing / Q000187:drug effects* / Q000276:immunology
chemical_list: D001843:Bone Cements; D018786:Bone Substitutes; D002130:Calcium Phosphates; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; C485838:calcium phosphate, monobasic, anhydrous; D020959:Polyethylene; D019904:Polymethyl Methacrylate; C020243:calcium phosphate; C485829:calcium phosphate, dibasic, anhydrous