title: Podoplanin immunopositive lymphatic vessels at the implant interface in a rat model of osteoporotic fractures.
abstract: Insertion of bone substitution materials accelerates healing of osteoporotic fractures. Biodegradable materials are preferred for application in osteoporotic patients to avoid a second surgery for implant replacement. Degraded implant fragments are often absorbed by macrophages that are removed from the fracture side via passage through veins or lymphatic vessels. We investigated if lymphatic vessels occur in osteoporotic bone defects and whether they are regulated by the use of different materials. To address this issue osteoporosis was induced in rats using the classical method of bilateral ovariectomy and additional calcium and vitamin deficient diet. In addition, wedge-shaped defects of 3, 4, or 5 mm were generated in the distal metaphyseal area of femur via osteotomy. The 4 mm defects were subsequently used for implantation studies where bone substitution materials of calcium phosphate cement, composites of collagen and silica, and iron foams with interconnecting pores were inserted. Different materials were partly additionally functionalized by strontium or bisphosphonate whose positive effects in osteoporosis treatment are well known. The lymphatic vessels were identified by immunohistochemistry using an antibody against podoplanin. Podoplanin immunopositive lymphatic vessels were detected in the granulation tissue filling the fracture gap, surrounding the implant and growing into the iron foam through its interconnected pores. Significant more lymphatic capillaries were counted at the implant interface of composite, strontium and bisphosphonate functionalized iron foam. A significant increase was also observed in the number of lymphatics situated in the pores of strontium coated iron foam. In conclusion, our results indicate the occurrence of lymphatic vessels in osteoporotic bone. Our results show that lymphatic vessels are localized at the implant interface and in the fracture gap where they might be involved in the removal of lymphocytes, macrophages, debris and the implants degradation products. Therefore the lymphatic vessels are involved in implant integration and fracture healing.
authors.affiliation: Laboratory of Experimental Trauma Surgery, Justus-Liebig University, Gießen, Germany.
authors.forename: Katrin Susanne
authors.initials: KS
authors.lastname: Lips
authors.forename: Vivien
authors.initials: V
authors.lastname: Kauschke
authors.forename: Sonja
authors.initials: S
authors.lastname: Hartmann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Thormann
authors.forename: Seemun
authors.initials: S
authors.lastname: Ray
authors.forename: Marian
authors.initials: M
authors.lastname: Kampschulte
authors.forename: Alexander
authors.initials: A
authors.lastname: Langheinrich
authors.forename: Matthias
authors.initials: M
authors.lastname: Schumacher
authors.forename: Michael
authors.initials: M
authors.lastname: Gelinsky
authors.forename: Sascha
authors.initials: S
authors.lastname: Heinemann
authors.forename: Thomas
authors.initials: T
authors.lastname: Hanke
authors.forename: Armin R
authors.initials: AR
authors.lastname: Kautz
authors.forename: Matthias
authors.initials: M
authors.lastname: Schnabelrauch
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schnettler
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.forename: Volker
authors.initials: V
authors.lastname: Alt
authors.forename: Olaf
authors.initials: O
authors.lastname: Kilian
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D018786:Bone Substitutes / Q000737:chemistry / Q000627:therapeutic use*; D003094:Collagen / Q000737:chemistry / Q000627:therapeutic use; D004164:Diphosphonates / Q000737:chemistry / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000473:pathology* / Q000601:surgery; D058085:Iron Compounds / Q000737:chemistry / Q000627:therapeutic use; D042601:Lymphatic Vessels / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000032:analysis*; D058866:Osteoporotic Fractures / Q000473:pathology* / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000737:chemistry / Q000627:therapeutic use; D013324:Strontium / Q000737:chemistry / Q000627:therapeutic use; D000098853:Podoplanin
chemical_list: D018786:Bone Substitutes; D003094:Collagen; D004164:Diphosphonates; D058085:Iron Compounds; D008562:Membrane Glycoproteins; D012822:Silicon Dioxide; D013324:Strontium; C092025:Pdpn protein, rat; D000098853:Podoplanin