Direct comparison of current cell-based and cell-free approaches towards the repair of craniofacial bone defects - A preclinical study.
For craniofacial bone defect repair, several alternatives to bone graft (BG) exist, including the combination of biphasic calcium phosphate (BCP) biomaterials with total bone marrow (TBM) and bone marrow-derived mesenchymal stromal cells (MSCs), or the use of growth factors like recombinant human bone morphogenic protein-2 (RhBMP-2) and various scaffolds. Therefore, clinicians might be unsure as to which approach will offer their patients the most benefit. Here, we aimed to compare different clinically relevant bone tissue engineering methods in an "all-in-one" study in rat calvarial defects. TBM, and MSCs committed or not, and cultured in two- or three-dimensions were mixed with BCP and implanted in bilateral parietal bone defects in rats. RhBMP-2 and BG were used as positive controls. After 7 weeks, significant de novo bone formation was observed in rhBMP-2 and BG groups, and in a lesser amount, when BCP biomaterials were mixed with TBM or committed MSCs cultured in three-dimensions. Due to the efficacy and safety of the TBM/BCP combination approach, we recommend this one-step procedure for further clinical investigation.


CONCLUSIONS
For craniofacial repair, total bone marrow (BM) and BM mesenchymal stem cell (MSC)-based regenerative medicine have shown to be promising in alternative to bone grafting (BG). Therefore, clinicians might be unsure as to which approach will offer the most benefit. Here, BM and MSCs committed or not were mixed with calcium phosphate ceramics (CaP) and implanted in bone defects in rats. RhBMP-2 and BG were used as positive controls. After 7 weeks, significant bone formation was observed in rhBMP-2 and BG groups, and when CaP were mixed with BM or committed MSCs. Since the BM-based procedure does not require bone harvest or cell culture, but provides de novo bone formation, we recommend consideration of this strategy for craniofacial applications.
INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, Laboratoire d'Ingénierie Ostéo-Articulaire et Dentaire, Groupe STEP "Skeletal Tissue Engineering and Physiopathology", 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; Centre Hospitalier Universitaire de Nantes, Clinique de Stomatologie et de Chirurgie maxillo-faciale, 1 place Alexis Ricordeau, 44093 Nantes Cedex 1, France; Université de Nantes, UFR Odontologie, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France. Electronic address: pierre.corre@chu-nantes.fr.
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Corre
INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, Laboratoire d'Ingénierie Ostéo-Articulaire et Dentaire, Groupe STEP "Skeletal Tissue Engineering and Physiopathology", 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; Université de Nantes, UFR Odontologie, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France.
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Merceron
Centre Hospitalier Universitaire de Nantes, Clinique de Stomatologie et de Chirurgie maxillo-faciale, 1 place Alexis Ricordeau, 44093 Nantes Cedex 1, France.
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Longis
AP-HP, Hôpital Pitié-Salpêtrière, Service de Chirurgie maxillo-faciale, Paris F-75013, France; UPMC Univ Paris 06, F-75005 Paris, France.
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Khonsari
INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, Laboratoire d'Ingénierie Ostéo-Articulaire et Dentaire, Groupe STEP "Skeletal Tissue Engineering and Physiopathology", 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; Université de Nantes, UFR Odontologie, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; Centre Hospitalier Universitaire de Nantes, PHU 4 OTONN, 1 place Alexis Ricordeau, 44093 Nantes Cedex 1, France.
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Pilet
INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, Laboratoire d'Ingénierie Ostéo-Articulaire et Dentaire, Groupe STEP "Skeletal Tissue Engineering and Physiopathology", 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; Université de Nantes, UFR Odontologie, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; Danang C Hospital, Dental surgery department, 122 Hai Phong Street, Hai Chau District, Danang city, Viet Nam.
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Thi
INSERM, UMR 957, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 1 rue Gaston Veil, 44035 Nantes Cedex 1, France; Université de Nantes, UFR Odontologie, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France.
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Battaglia
INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, Laboratoire d'Ingénierie Ostéo-Articulaire et Dentaire, Groupe STEP "Skeletal Tissue Engineering and Physiopathology", 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; Université de Nantes, UFR Odontologie, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France.
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Sourice
INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, Laboratoire d'Ingénierie Ostéo-Articulaire et Dentaire, Groupe STEP "Skeletal Tissue Engineering and Physiopathology", 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; Université de Nantes, UFR Odontologie, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France.
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Masson
INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, Laboratoire d'Ingénierie Ostéo-Articulaire et Dentaire, Groupe STEP "Skeletal Tissue Engineering and Physiopathology", 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; Université de Nantes, UFR Odontologie, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France.
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Sohier
INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, Laboratoire d'Ingénierie Ostéo-Articulaire et Dentaire, Groupe STEP "Skeletal Tissue Engineering and Physiopathology", 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; Centre Hospitalier Universitaire de Nantes, Clinique d'Oto-Rhino-Laryngologie et de Chirurgie cervico-faciale, 1 place Alexis Ricordeau, 44093 Nantes Cedex 1, France; Université de Nantes, UFR Odontologie, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France.
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Espitalier
INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, Laboratoire d'Ingénierie Ostéo-Articulaire et Dentaire, Groupe STEP "Skeletal Tissue Engineering and Physiopathology", 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; Université de Nantes, UFR Odontologie, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; Centre Hospitalier Universitaire de Nantes, PHU 4 OTONN, 1 place Alexis Ricordeau, 44093 Nantes Cedex 1, France.
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Guicheux
INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, Laboratoire d'Ingénierie Ostéo-Articulaire et Dentaire, Groupe STEP "Skeletal Tissue Engineering and Physiopathology", 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; Université de Nantes, UFR Odontologie, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; Centre Hospitalier Universitaire de Nantes, PHU 4 OTONN, 1 place Alexis Ricordeau, 44093 Nantes Cedex 1, France.
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Weiss
D000818:Animals; D018786:Bone Substitutes / Q000627:therapeutic use*; D002474:Cell-Free System; D019465:Craniofacial Abnormalities / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000601:surgery*; D048091:Guided Tissue Regeneration / Q000295:instrumentation*; D010012:Osteogenesis / Q000502:physiology; D011859:Radiography; D051381:Rats; D011917:Rats, Inbred Lew; D033581:Stem Cell Transplantation / Q000295:instrumentation*; D054457:Tissue Scaffolds; D016896:Treatment Outcome
D018786:Bone Substitutes
Bone graft; Bone marrow; Bone tissue engineering; Calcium phosphate; Calvaria; Mesenchymal stromal cells