title: Calcium-phosphate ceramics and polysaccharide-based hydrogel scaffolds combined with mesenchymal stem cell differently support bone repair in rats.
abstract: Research in bone tissue engineering is focused on the development of alternatives to autologous bone grafts for bone reconstruction. Although multiple stem cell-based products and biomaterials are currently being investigated, comparative studies are rarely achieved to evaluate the most appropriate approach in this context. Here, we aimed to compare different clinically relevant bone tissue engineering methods and evaluated the kinetic repair and the bone healing efficiency supported by mesenchymal stem cells and two different biomaterials, a new hydrogel scaffold and a commercial hydroxyapatite/tricalcium phosphate ceramic, alone or in combination.Syngeneic mesenchymal stem cells (5 × 105) and macroporous biphasic calcium phosphate ceramic granules (Calciresorb C35®, Ceraver) or porous pullulan/dextran-based hydrogel scaffold were implanted alone or combined in a drilled-hole bone defect in rats. Using quantitative microtomography measurements and qualitative histological examinations, their osteogenic properties were evaluated 7, 30, and 90 days after implantation. Three months after surgery, only minimal repair was evidenced in control rats while newly mineralized bone was massively observed in animals treated with either hydrogels (bone volume/tissue volume = 20%) or ceramics (bone volume/tissue volume = 26%). Repair mechanism and resorption kinetics were strikingly different: rapidly-resorbed hydrogels induced a dense bone mineralization from the edges of the defect while ceramics triggered newly woven bone formation in close contact with the ceramic surface that remained unresorbed. Delivery of mesenchymal stem cells in combination with these biomaterials enhanced both bone healing (>20%) and neovascularization after 1 month, mainly in hydrogel.Osteogenic and angiogenic properties combined with rapid resorption make hydrogels a promising alternative to ceramics for bone repair by cell therapy.
authors.affiliation: Département Soutien Médico-Chirurgical des Forces, Institut de Recherche Biomédicale des Armées (IRBA), BP 73, 91223, Brétigny-sur-Orge cedex, France. sfrasca.irba@gmail.com.
authors.forename: Sophie
authors.identifier: http://orcid.org/0000-0002-1304-952X
authors.initials: S
authors.lastname: Frasca
authors.affiliation: AP-HP, Service de Biothérapie, Hôpital de la Pitié Salpêtrière, Paris, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Norol
authors.affiliation: INSERM U791, Centre for Osteoarticular and Dental Tissue Engineering, Nantes, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Le Visage
authors.affiliation: Département Soutien Médico-Chirurgical des Forces, Institut de Recherche Biomédicale des Armées (IRBA), BP 73, 91223, Brétigny-sur-Orge cedex, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Collombet
authors.affiliation: INSERM U1148, LVTS, Université Paris 13, Hôpital X. Bichat, Université Paris Diderot, Paris, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Letourneur
authors.affiliation: Département Soutien Médico-Chirurgical des Forces, Institut de Recherche Biomédicale des Armées (IRBA), BP 73, 91223, Brétigny-sur-Orge cedex, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Holy
authors.affiliation: AP-HP, Département de Chirurgie Orthopédique et Traumatologie, Hôpital de la Pitié Salpêtrière, Paris, France.
authors.forename: Elhadi
authors.initials: E
authors.lastname: Sari Ali
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001854:Bone Marrow Cells / Q000166:cytology; D001861:Bone Regeneration; D001862:Bone Resorption; D016025:Bone Transplantation / Q000379:methods; D002130:Calcium Phosphates / Q000737:chemistry*; D002516:Ceramics / Q000737:chemistry; D005269:Femur / Q000473:pathology; D020100:Hydrogels / Q000737:chemistry*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009389:Neovascularization, Pathologic; D011134:Polysaccharides / Q000737:chemistry*; D051381:Rats; D011917:Rats, Inbred Lew; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*; D055114:X-Ray Microtomography
chemical_list: D001672:Biocompatible Materials; D002130:Calcium Phosphates; D020100:Hydrogels; D011134:Polysaccharides; C020243:calcium phosphate