Bone regeneration strategies: Engineered scaffolds, bioactive molecules and stem cells current stage and future perspectives

Inc O. The Orthopaedic Industry Annual Report: 2010-2011. In: Inc O, editor. Ohio, Chagrin Falls 44 0232010–0232011. Holmes, 2017, Non-union bone fracture: a quicker fix, Nature, 550, S193, 10.1038/550S193a Holmes, 2017, Closing the gap, Nature, 550, S194, 10.1038/550S194a Seeman, 2008, Bone quality: the material and structural basis of bone strength, J. Bone Miner. Metabol., 26, 1, 10.1007/s00774-007-0793-5 Gerstenfeld, 2003, Fracture healing as a post-natal developmental process: molecular, spatial, and temporal aspects of its regulation, J. Cell. Biochem., 88, 873, 10.1002/jcb.10435 Phillips, 2005, Overview of the fracture healing cascade, Injury, 36, S5, 10.1016/j.injury.2005.07.027 Claes, 2012, Fracture healing under healthy and inflammatory conditions, Nat. Rev. Rheumatol., 8, 133, 10.1038/nrrheum.2012.1 Kolar, 2010, The early fracture hematoma and its potential role in fracture healing, Tissue Eng. B Rev., 16, 427, 10.1089/ten.teb.2009.0687 Street, 2000, Is human fracture hematoma inherently angiogenic?, Clin. Orthop. Relat. Res., 224, 10.1097/00003086-200009000-00033 Prystaz, 2018, Distinct effects of IL-6 classic and trans-signaling in bone fracture healing, Am. J. Pathol., 188, 474, 10.1016/j.ajpath.2017.10.011 Schlundt, 2018, Macrophages in bone fracture healing: their essential role in endochondral ossification, Bone, 106, 78, 10.1016/j.bone.2015.10.019 Gerstenfeld, 2003, Impaired fracture healing in the absence of TNF-alpha signaling: the role of TNF-alpha in endochondral cartilage resorption, J. Bone Miner. Res., 18, 1584, 10.1359/jbmr.2003.18.9.1584 Yang, 2007, Callus mineralization and maturation are delayed during fracture healing in interleukin-6 knockout mice, Bone, 41, 928, 10.1016/j.bone.2007.07.022 Raggatt, 2014, Fracture healing via periosteal callus formation requires macrophages for both initiation and progression of early endochondral ossification, Am. J. Pathol., 184, 3192, 10.1016/j.ajpath.2014.08.017 Hall, 2000, All for one and one for all: condensations and the initiation of skeletal development, Bioessays, 22, 138, 10.1002/(SICI)1521-1878(200002)22:2<138::AID-BIES5>3.0.CO;2-4 Hall, 1995, Divide, accumulate, differentiate: cell condensation in skeletal development revisited, Int. J. Dev. Biol., 39, 881 Dunlop, 1995, Relationships between cellular condensation, preosteoblast formation and epithelial-mesenchymal interactions in initiation of osteogenesis, Int. J. Dev. Biol., 39, 357 Colnot, 2009, Skeletal cell fate decisions within periosteum and bone marrow during bone regeneration, J. Bone Miner. Res., 24, 274, 10.1359/jbmr.081003 Duchamp de Lageneste, 2018, Periosteum contains skeletal stem cells with high bone regenerative potential controlled by Periostin, Nat. Commun., 9, 773, 10.1038/s41467-018-03124-z Schindeler, 2008, Bone remodeling during fracture repair: the cellular picture, Semin. Cell Dev. Biol., 19, 459, 10.1016/j.semcdb.2008.07.004 Ai-Aql, 2008, Molecular mechanisms controlling bone formation during fracture healing and distraction osteogenesis, J. Dent. Res., 87, 107, 10.1177/154405910808700215 Riddle, 2017, Bone cell bioenergetics and skeletal energy homeostasis, Physiol. Rev., 97, 667, 10.1152/physrev.00022.2016 Thompson, 2002, A model for intramembranous ossification during fracture healing, J. Orthop. Res., 20, 1091, 10.1016/S0736-0266(02)00017-7 Shen, 2009, Prolyl hydroxylase inhibitors increase neoangiogenesis and callus formation following femur fracture in mice, J. Orthop. Res., 27, 1298, 10.1002/jor.20886 Barnes, 1999, Growth factor regulation of fracture repair, J. Bone Miner. Res., 14, 1805, 10.1359/jbmr.1999.14.11.1805 Gerstenfeld, 2001, Impaired intramembranous bone formation during bone repair in the absence of tumor necrosis factor-alpha signaling, Cells Tissues Organs, 169, 285, 10.1159/000047893 Schmid, 2009, Fibroblast growth factor expression during skeletal fracture healing in mice, Dev. Dynam., 238, 766, 10.1002/dvdy.21882 Yu, 2010, Immunolocalization of BMPs, BMP antagonists, receptors, and effectors during fracture repair, Bone, 46, 841, 10.1016/j.bone.2009.11.005 Giannoudis, 2005, Bone substitutes: an update, Injury, 36, S20, 10.1016/j.injury.2005.07.029 Laurencin, 2006, Bone graft substitutes, Expet Rev. Med. Dev., 3, 49, 10.1586/17434440.3.1.49 Vanderstappen, 2015, Ilizarov bone transport as a treatment of congenital pseudarthrosis of the tibia: a long-term follow-up study, J. Child. Orthop., 9, 319, 10.1007/s11832-015-0675-7 Einhorn, 2015, Fracture healing: mechanisms and interventions, Nat. Rev. Rheumatol., 11, 45, 10.1038/nrrheum.2014.164 Eaton, 2015, Delivering nanomedicines to patients: a practical guide, Nanomed. Nanotechnol. Biol. Med., 11, 983, 10.1016/j.nano.2015.02.004 Hollister, 2011, Scaffold translation: barriers between concept and clinic, Tissue Eng. B Rev., 17, 459, 10.1089/ten.teb.2011.0251 Volk, 2015, Key elements for nourishing the translational research environment, Sci. Transl. Med., 7, 4, 10.1126/scitranslmed.aaa2049 Bara, 2016, Improving translation success of cell-based therapies in orthopaedics, J. Orthop. Res., 34, 17, 10.1002/jor.23055 Reichert, 2009, The challenge of establishing preclinical models for segmental bone defect research, Biomaterials, 30, 2149, 10.1016/j.biomaterials.2008.12.050 Li, 2015, Bone defect animal models for testing efficacy of bone substitute biomaterials, J. Orthop. Transl., 3, 95 Wancket, 2015, Animal models for evaluation of bone implants and devices: comparative bone structure and common model uses, Vet. Pathol., 52, 842, 10.1177/0300985815593124 Peric, 2015, The rational use of animal models in the evaluation of novel bone regenerative therapies, Bone, 70, 73, 10.1016/j.bone.2014.07.010 Lammens, 2017, Warning about the use of critical-size defects for the translational study of bone repair: analysis of a sheep tibial model, Tissue Eng. C Meth., 23, 694, 10.1089/ten.tec.2017.0147 Szpalski, 2012, Bone tissue engineering: current strategies and Techniques-Part I: scaffolds, Tissue Eng. B Rev., 18, 246, 10.1089/ten.teb.2011.0427 Amini, 2012, Optimally porous and biomechanically compatible scaffolds for large-area bone regeneration, Tissue Eng., 18, 1376, 10.1089/ten.tea.2011.0076 Tan, 2017, Metallic powder-bed based 3D printing of cellular scaffolds for orthopaedic implants: a state-of-the-art review on manufacturing, topological design, mechanical properties and biocompatibility, Mater. Sci. Eng. C Mater. Biol. Appl., 76, 1328, 10.1016/j.msec.2017.02.094 Mustafa, 2011, Customized titanium reconstruction of post-traumatic orbital wall defects: a review of 22 cases, Int. J. Oral Maxillofac. Surg., 40, 1357, 10.1016/j.ijom.2011.04.020 Li, 2017, Multilevel 3D printing implant for reconstructing cervical spine with metastatic papillary thyroid carcinoma, Spine (Phila Pa 1976), 42, E1326, 10.1097/BRS.0000000000002229 Yang, 2017, Laser beam melting 3D printing of Ti6Al4V based porous structured dental implants: fabrication, biocompatibility analysis and photoelastic study, Sci. Rep., 7, 45360, 10.1038/srep45360 Xie, 2016, Net shape fabrication of calcium phosphate scaffolds with multiple material domains, Biofabrication, 8, 10.1088/1758-5090/8/1/015005 Ng, 2014, Computer-designed PEEK implants: a peek into the future of cranioplasty?, J. Craniofac. Surg., 25, e55, 10.1097/SCS.0b013e3182a2f7b6 Tack, 2016, 3D-printing techniques in a medical setting: a systematic literature review, Biomed. Eng. Online, 15, 115, 10.1186/s12938-016-0236-4 Colquhoun, 2016, Mechanical behaviour of degradable phosphate glass fibres and composites-a review, Biomed. Mater., 11, 18 Fernandez-Yague, 2015, Biomimetic approaches in bone tissue engineering: integrating biological and physicomechanical strategies, Adv. Drug Deliv. Rev., 84, 1, 10.1016/j.addr.2014.09.005 Babaie, 2018, Fabrication aspects of porous biomaterials in orthopedic applications: a review, ACS Biomater. Sci. Eng., 4, 1, 10.1021/acsbiomaterials.7b00615 Mumith, 2017, Augmenting the osseointegration of endoprostheses using laser-sintered porous collars: an in vivo study, Bone Joint J., 99B, 276, 10.1302/0301-620X.99B2.BJJ-2016-0584.R1 Polak, 2011, Analysis of the roles of microporosity and BMP-2 on multiple measures of bone regeneration and healing in calcium phosphate scaffolds, Acta Biomater., 7, 1760, 10.1016/j.actbio.2010.12.030 Rustom, 2017, Multiscale porosity directs bone regeneration in biphasic calcium phosphate scaffolds, ACS Biomater. Sci. Eng., 3, 2768, 10.1021/acsbiomaterials.6b00632 Ciocca, 2017, Customized hybrid biomimetic hydroxyapatite scaffold for bone tissue regeneration, J. Biomed. Mater. Res. Part B, 105, 723, 10.1002/jbm.b.33597 Yang, 2017, 3D-printed bioactive Ca3SiO5 bone cement scaffolds with nano surface structure for bone regeneration, ACS Appl. Mater. Interfaces, 9, 5757, 10.1021/acsami.6b14297 Bandyopadhyay, 2017, In vivo response of laser processed porous titanium implants for load-bearing implants, Ann. Biomed. Eng., 45, 249, 10.1007/s10439-016-1673-8 Braem, 2014, Peri- and intra-implant bone response to microporous Ti coatings with surface modification, Acta Biomater., 10, 986, 10.1016/j.actbio.2013.10.017 Kamitakahara, 2016, Effect of silicate incorporation on in vivo responses of alpha-tricalcium phosphate ceramics, J. Mater. Sci. Mater. Med., 27, 9, 10.1007/s10856-016-5706-5 Garcia-Gareta, 2018, Biomimetic surface functionalization of clinically relevant metals used as orthopaedic and dental implants, Biomed. Mater., 13, 14 Hao, 2017, Biological and mechanical effects of micro-nanostructured titanium surface on an osteoblastic cell Line in vitro and osteointegration in vivo, Appl. Biochem. Biotechnol., 183, 280, 10.1007/s12010-017-2444-1 Heo, 2016, Titanium dental implants surface-immobilized with gold nanoparticles as osteoinductive agents for rapid osseointegration, J. Colloid Interface Sci., 469, 129, 10.1016/j.jcis.2016.02.022 Hou, 2018, Hybrid micro/nanostructural surface offering improved stress distribution and enhanced osseointegration properties of the biomedical titanium implant, J. Mech. Behav. Biomed. Mater., 79, 173, 10.1016/j.jmbbm.2017.11.042 Mroz, 2015, In vivo implantation of porous titanium alloy implants coated with magnesium-doped octacalcium phosphate and hydroxyapatite thin films using pulsed laser depostion, J. Biomed. Mater. Res. Part B, 103, 151, 10.1002/jbm.b.33170 Covarrubias, 2016, Osseointegration properties of titanium dental implants modified with a nanostructured coating based on ordered porous silica and bioactive glass nanoparticles, Appl. Surf. Sci., 363, 286, 10.1016/j.apsusc.2015.12.022 Caparros, 2016, Bioactive macroporous titanium implants highly interconnected, J. Mater. Sci. Mater. Med., 27, 11, 10.1007/s10856-016-5764-8 Krishnan, 2006, Regulation of bone mass by Wnt signaling, J. Clin. Invest., 116, 1202, 10.1172/JCI28551 Santo, 2013, Controlled release strategies for bone, cartilage, and osteochondral engineering–Part I: recapitulation of native tissue healing and variables for the design of delivery systems, Tissue Eng. B Rev., 19, 308, 10.1089/ten.teb.2012.0138 Carragee, 2011, A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned, Spine J., 11, 471, 10.1016/j.spinee.2011.04.023 Simmonds, 2010, 2013 Zara, 2011, High doses of bone morphogenetic protein 2 induce structurally abnormal bone and inflammation in vivo, Tissue Eng., 17, 1389, 10.1089/ten.tea.2010.0555 Kim, 2012, Volumetric bone regenerative efficacy of biphasic calcium phosphate-collagen composite block loaded with rhBMP-2 in vertical bone augmentation model of a rabbit calvarium, J. Biomed. Mater. Res., 100, 3304, 10.1002/jbm.a.34278 Hwang, 2016, Bone regenerative effect of recombinant human bone morphogenetic protein-2 after cyst enucleation, Maxillofac. Plast. Reconstr. Surg., 38, 22, 10.1186/s40902-016-0070-4 Cho, 2017, Efficacy of Escherichia coli-derived recombinant human bone morphogenetic protein-2 in posterolateral lumbar fusion: an open, active-controlled, randomized, multicenter trial, Spine J., 17, 1866, 10.1016/j.spinee.2017.06.023 King, 2012, Growth factor delivery: how surface interactions modulate release in vitro and in vivo, Adv. Drug Deliv. Rev., 64, 1239, 10.1016/j.addr.2012.03.004 El Bialy, 2017, Formulation, delivery and stability of bone morphogenetic proteins for effective bone regeneration, Pharm Res., 34, 1152, 10.1007/s11095-017-2147-x Yu, 2015, How does the pathophysiological context influence delivery of bone growth factors?, Adv. Drug Deliv. Rev., 84, 68, 10.1016/j.addr.2014.10.010 Bouyer, 2016, Surface delivery of tunable doses of BMP-2 from an adaptable polymeric scaffold induces volumetric bone regeneration, Biomaterials, 104, 168, 10.1016/j.biomaterials.2016.06.001 Cecchi, 2016, Bone morphogenetic protein-7: review of signalling and efficacy in fracture healing, J. Orthop. Transl., 4, 28 Wei, 2016, Roles of the kidney in the formation, remodeling and repair of bone, J. Nephrol., 29, 349, 10.1007/s40620-016-0284-7 Reichert, 2012, A tissue engineering solution for segmental defect regeneration in load-bearing long bones, Sci. Transl. Med., 4, 141ra93, 10.1126/scitranslmed.3003720 Ozaki, 2007, Comprehensive analysis of chemotactic factors for bone marrow mesenchymal stem cells, Stem Cell. Dev., 16, 119, 10.1089/scd.2006.0032 DiGiovanni, 2013, North Amer Orthopedic Foot Ankle S. Recombinant human platelet-derived growth factor-BB and beta-tricalcium phosphate (rhPDGF-BB/beta-TCP): an alternative to autogenous bone graft, J. Bone Joint Surg-Am, 95A, 1184, 10.2106/JBJS.K.01422 DiGiovanni, 2016, The importance of sufficient graft material in achieving foot or ankle fusion, J. Bone Joint Surg-Am, 98, 1260, 10.2106/JBJS.15.00879 Jin, 2013, Growth differentiation factor 5 regulation in bone regeneration, Curr. Pharmaceut. Des., 19, 3364, 10.2174/1381612811319190003 Erlacher, 1998, Cartilage-derived morphogenetic proteins and osteogenic protein-1 differentially regulate osteogenesis, J. Bone Miner. Res. Off. J. Am. Soc. Bone Min. Res., 13, 383, 10.1359/jbmr.1998.13.3.383 Cui, 2008, Mouse growth and differentiation factor-5 protein and DNA therapy potentiates intervertebral disc cell aggregation and chondrogenic gene expression, Spine J., 8, 287, 10.1016/j.spinee.2007.05.012 Kleinschmidt, 2013, Enhanced reconstruction of long bone architecture by a growth factor mutant combining positive features of GDF-5 and BMP-2, Biomaterials, 34, 5926, 10.1016/j.biomaterials.2013.04.029 Kleinschmidt, 2014, Superior angiogenic potential of GDF-5 and GDF-5(V453/V456) compared with BMP-2 in a rabbit long-bone defect model, J. Bone Joint Surg. Am., 96, 1699, 10.2106/JBJS.M.01462 Yang, 2017, Surface modification of titanium with BMP-2/GDF-5 by a heparin linker and its efficacy as a dental implant, Int. J. Mol. Sci., 18, 16 Roh, 2013, Allogeneic morphogenetic protein vs. recombinant human bone morphogenetic protein-2 in lumbar interbody fusion procedures: a radiographic and economic analysis, J. Orthop. Surg. Res., 8, 49, 10.1186/1749-799X-8-49 Vukicevic, 2014, The clinical use of bone morphogenetic proteins revisited: a novel biocompatible Carrier device OSTEOGROW for bone healing, Int. Orthop., 38, 635, 10.1007/s00264-013-2201-1 Lin, 2012, B2A as a positive BMP receptor modulator, Growth Factors, 30, 149, 10.3109/08977194.2012.671310 Liu, 2012, B2A, a receptor modulator, increases the growth of pluripotent and preosteoblast cells through bone morphogenetic protein receptors, Growth Factors, 30, 410, 10.3109/08977194.2012.745520 Cunningham, 2009, Ceramic granules enhanced with B2A peptide for lumbar interbody spine fusion: an experimental study using an instrumented model in sheep Laboratory investigation, J. Neurosurg. Spine, 10, 300, 10.3171/2009.1.SPINE08565 Zamora, 2013, Biocompatibility and inflammation profile of B2A-coated granules used in arthrodesis, Int. J. Toxicol., 32, 154, 10.1177/1091581813476960 Qian, 1996, Enhanced cell attachment to anorganic bone mineral in the presence of a synthetic peptide related to collagen, J. Biomed. Mater. Res., 31, 545, 10.1002/(SICI)1097-4636(199608)31:4<545::AID-JBM15>3.0.CO;2-F Nguyen, 2003, Enhanced cell attachment and osteoblastic activity by P-15 peptide-coated matrix in hydrogels, Biochem. Biophys. Res. Commun., 311, 179, 10.1016/j.bbrc.2003.09.192 Hennessy, 2009, The effect of collagen I mimetic peptides on mesenchymal stem cell adhesion and differentiation, and on bone formation at hydroxyapatite surfaces, Biomaterials, 30, 1898, 10.1016/j.biomaterials.2008.12.053 Gomar, 2007, P-15 small peptide bone graft substitute in the treatment of non-unions and delayed union. A pilot clinical trial, Int. Orthop., 31, 93, 10.1007/s00264-006-0087-x Sherman, 2010, Evaluation of ABM/P-15 versus autogenous bone in an ovine lumbar interbody fusion model, Eur. Spine J., 19, 2156, 10.1007/s00586-010-1546-z Lauweryns, 2015, Prospective analysis of a new bone graft in lumbar interbody fusion: results of a 2- year prospective clinical and radiological study, Internet J. Spine Surg., 9 Arnold, 2016, Efficacy of i-Factor bone graft versus autograft in anterior cervical discectomy and fusion: results of the prospective, randomized, single-blinded food and drug administration investigational device exemption study, Spine (Phila Pa 1976), 41, 1075, 10.1097/BRS.0000000000001466 Zouani, 2010, Differentiation of pre-osteoblast cells on poly(ethylene terephthalate) grafted with RGD and/or BMPs mimetic peptides, Biomaterials, 31, 8245, 10.1016/j.biomaterials.2010.07.042 Moeinzadeh, 2015, Morphogenic peptides in regeneration of load bearing tissues, 95 Mueller, 2012, Promiscuity and specificity in BMP receptor activation, FEBS Lett., 586, 1846, 10.1016/j.febslet.2012.02.043 Lombardi, 2011, The roles of parathyroid hormone in bone remodeling: prospects for novel therapeutics, J. Endocrinol. Invest., 34, 18 Arrighi, 2009, Bone healing induced by local delivery of an engineered parathyroid hormone prodrug, Biomaterials, 30, 1763, 10.1016/j.biomaterials.2008.12.023 Fuerst, 2007, Use of a parathyroid hormone peptide (PTH(1-34))-enriched fibrin hydrogel for the treatment of a subchondral cystic lesion in the proximal interphalangeal joint of a warmblood filly. Journal of veterinary medicine A, Physiol. Pathol. Clin. Med., 54, 107, 10.1111/j.1439-0442.2007.00890.x Zhang, 2010, The role of NELL-1, a growth factor associated with craniosynostosis, in promoting bone regeneration, J. Dent. Res., 89, 865, 10.1177/0022034510376401 Siu, 2012, NELL-1 promotes cartilage regeneration in an in vivo rabbit model, Tissue Eng., 18, 252, 10.1089/ten.tea.2011.0142 Askarinam, 2013, Human perivascular stem cells show enhanced osteogenesis and vasculogenesis with Nel-like molecule I protein, Tissue Eng., 19, 1386, 10.1089/ten.tea.2012.0367 Pang, 2015, Proliferation and osteogenic differentiation of mesenchymal stem cells induced by a short isoform of NELL-1, Stem Cell., 33, 904, 10.1002/stem.1884 James, 2015, NELL-1 in the treatment of osteoporotic bone loss, Nat. Commun., 6, 7362, 10.1038/ncomms8362 James, 2017, NELL-1 induces Sca-1+ mesenchymal progenitor cell expansion in models of bone maintenance and repair, JCI Insight, 2 Tanjaya, 2018, The effects of systemic therapy of PEGylated NELL-1 on fracture healing in mice, Am. J. Pathol., 188, 715, 10.1016/j.ajpath.2017.11.018 Sangadala, 2006, LIM mineralization protein-1 potentiates bone morphogenetic protein responsiveness via a novel interaction with Smurf1 resulting in decreased ubiquitination of Smads, J. Biol. Chem., 281, 17212, 10.1074/jbc.M511013200 Pan, 2015, LIM mineralization protein-1 enhances bone morphogenetic protein-2-mediated osteogenesis through activation of ERK1/2 MAPK pathway and upregulation of runx2 Transactivity, J. Bone Miner. Res., 30, 1523, 10.1002/jbmr.2481 Strohbach, 2008, LMP-1 retroviral gene therapy influences osteoblast differentiation and fracture repair: a preliminary study, Calcif. Tissue Int., 83, 202, 10.1007/s00223-008-9163-0 Florio, 2016, A bispecific antibody targeting sclerostin and DKK-1 promotes bone mass accrual and fracture repair, Nat. Commun., 7, 14, 10.1038/ncomms11505 Bolander, 2017, Healing of a large long-bone defect through serum-free Iin vitro priming of human periosteum-derived cells, Stem Cell Rep., 8, 758, 10.1016/j.stemcr.2017.01.005 Bolander, 2016, The combined mechanism of bone morphogenetic protein- and calcium phosphate-induced skeletal tissue formation by human periosteum derived cells, Eur. Cell. Mater., 31, 11, 10.22203/eCM.v031a02 Ingber, 2006, Tissue engineering and developmental biology: going biomimetic, Tissue Eng., 12, 3265, 10.1089/ten.2006.12.3265 Lenas, 2009, Developmental engineering: a new paradigm for the design and manufacturing of cell-based products. Part I: from three-dimensional cell growth to biomimetics of in vivo development, Tissue Eng. B Rev., 15, 381, 10.1089/ten.teb.2008.0575 Lenas, 2009, Developmental engineering: a new paradigm for the design and manufacturing of cell-based products. Part II: from genes to networks: tissue engineering from the viewpoint of systems biology and network science, Tissue Eng. B Rev., 15, 395, 10.1089/ten.teb.2009.0461 Friedenstein, 1966, Osteogenesis in transplants of bone marrow cells, J. Embryol. Exp. Morphol., 16, 381 Friedenstein, 1968, Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues, Transplantation, 6, 230, 10.1097/00007890-196803000-00009 Martinez, 1999, Influence of skeletal site of origin and donor age on osteoblastic cell growth and differentiation, Calcif. Tissue Int., 64, 280, 10.1007/s002239900619 Greco, 2007, Functional similarities among genes regulated by OCT4 in human mesenchymal and embryonic stem cells, Stem Cell., 25, 3143, 10.1634/stemcells.2007-0351 Ding, 2015, Human umbilical cord mesenchymal stem cells: a new era for stem cell therapy, Cell Transplant., 24, 339, 10.3727/096368915X686841 Bianco, 2013, The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine, Nat. Med., 19, 35, 10.1038/nm.3028 Heathman, 2015, The translation of cell-based therapies: clinical landscape and manufacturing challenges, Regen. Med., 10, 49, 10.2217/rme.14.73 Lin, 2002, The stem-cell niche theory: lessons from flies, Nat. Rev. Genet., 3, 931, 10.1038/nrg952 Lei, 2014, Mathematical model of adult stem cell regeneration with cross-talk between genetic and epigenetic regulation, Proc. Natl. Acad. Sci. U. S. A., 111, E880, 10.1073/pnas.1324267111 Elsafadi, 2016, Characterization of cellular and molecular heterogeneity of bone marrow stromal cells, Stem Cell. Int., 2016 Bianco, 2001, Bone marrow stromal stem cells: nature, biology, and potential applications, Stem Cell., 19, 180, 10.1634/stemcells.19-3-180 Hernigou, 2006, Percutaneous autologous bone-marrow grafting for nonunions. Surgical technique, J. Bone Joint Surg. Am., 88, 322, 10.2106/00004623-200609001-00015 Devine, 2002, Transplanted bone marrow cells localize to fracture callus in a mouse model, J. Orthop. Res., 20, 1232, 10.1016/S0736-0266(02)00051-7 Friedenstein, 1974, Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method, Exp. Hematol., 2, 83 Amable, 2014, Mesenchymal stromal cell proliferation, gene expression and protein production in human platelet-rich plasma-supplemented media, PLoS One, 9, e104662, 10.1371/journal.pone.0104662 Muraglia, 2000, Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model, J. Cell Sci., 113, 1161, 10.1242/jcs.113.7.1161 Minieri, 2015, Persistent DNA damage-induced premature senescence alters the functional features of human bone marrow mesenchymal stem cells, J. Cell Mol. Med., 19, 734, 10.1111/jcmm.12387 Szpalski, 2012, Bone tissue engineering: current strategies and techniques-part II: cell types, Tissue Eng. B Rev., 18, 258, 10.1089/ten.teb.2011.0440 Colnot, 2006, Analyzing the cellular contribution of bone marrow to fracture healing using bone marrow transplantation in mice, Biochem. Biophy. Res. Commun., 350, 557, 10.1016/j.bbrc.2006.09.079 Bunnell, 2008, Adipose-derived stem cells: isolation, expansion and differentiation, Methods, 45, 115, 10.1016/j.ymeth.2008.03.006 El-Badawy, 2017, Adipose-derived stem cell-based therapies in regenerative medicine, Stem Cells Biol. Reg., 117 Aust, 2004, Yield of human adipose-derived adult stem cells from liposuction aspirates, Cytotherapy, 6, 7, 10.1080/14653240310004539 Zuk, 2001, Multilineage cells from human adipose tissue: implications for cell-based therapies, Tissue Eng., 7, 211, 10.1089/107632701300062859 Cui, 2007, Expanded adipose-derived stem cells suppress mixed lymphocyte reaction by secretion of prostaglandin E2, Tissue Eng., 13, 1185, 10.1089/ten.2006.0315 Puissant, 2005, Immunomodulatory effect of human adipose tissue-derived adult stem cells: comparison with bone marrow mesenchymal stem cells, Br. J. Haematol., 129, 118, 10.1111/j.1365-2141.2005.05409.x Cowan, 2004, Adipose-derived adult stromal cells heal critical-size mouse calvarial defects, Nat. Biotechnol., 22, 560, 10.1038/nbt958 McIntosh, 2009, Immunogenicity of allogeneic adipose-derived stem cells in a rat spinal fusion model, Tissue Eng., 15, 2677, 10.1089/ten.tea.2008.0566 Lopez, 2009, Acceleration of spinal fusion using syngeneic and allogeneic adult adipose derived stem cells in a rat model, J. Orthop. Res., 27, 366, 10.1002/jor.20735 Lee, 2012, Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration, Stem Cell Res. Ther., 3, 35, 10.1186/scrt126 Mesimaki, 2009, Novel maxillary reconstruction with ectopic bone formation by GMP adipose stem cells, Int. J. Oral Maxillofac. Surg., 38, 201, 10.1016/j.ijom.2009.01.001 Bailey, 2010, Characterization of adipose-derived stem cells: an update, Curr. Stem Cell Res. Ther., 5, 95, 10.2174/157488810791268555 Oedayrajsingh-Varma, 2006, Adipose tissue-derived mesenchymal stem cell yield and growth characteristics are affected by the tissue-harvesting procedure, Cytotherapy, 8, 166, 10.1080/14653240600621125 Roberts, 2015, Uncovering the periosteum for skeletal regeneration: the stem cell that lies beneath, Bone, 70, 10, 10.1016/j.bone.2014.08.007 Moore, 2014, Periosteal thickness and cellularity in mid-diaphyseal cross-sections from human femora and tibiae of aged donors, J. Anat., 224, 142 Allen, 2004, Periosteum: biology, regulation, and response to osteoporosis therapies, Bone, 35, 1003, 10.1016/j.bone.2004.07.014 Clarke, 2008, Normal bone anatomy and physiology, Clin. J. Am. Soc. Nephrol., 3, S131, 10.2215/CJN.04151206 Chang, 2012, Concise review: the periosteum: tapping into a reservoir of clinically useful progenitor cells, Stem Cell. Transl. Med., 1, 480, 10.5966/sctm.2011-0056 De Bari, 2006, Mesenchymal multipotency of adult human periosteal cells demonstrated by single-cell lineage analysis, Arthritis Rheum., 54, 1209, 10.1002/art.21753 Lambrechts, 2016, Large-scale progenitor cell expansion for multiple donors in a monitored hollow fibre bioreactor, Cytotherapy, 18, 1219, 10.1016/j.jcyt.2016.05.013 Eyckmans, 2013, Mapping calcium phosphate activated gene networks as a strategy for targeted osteoinduction of human progenitors, Biomaterials, 34, 4612, 10.1016/j.biomaterials.2013.03.011 Bolander, 2016, Wnt and Ca(2+)/PKC pathway activation predicts the bone forming capacity of periosteal cells in combination with calcium phosphates, Biomaterials, 86, 106, 10.1016/j.biomaterials.2016.01.059 Ryan, 1979, Effect of different fetal bovine serum concentrations on the replicative life span of cultured chick cells, In Vitro, 15, 895 Jung, 2012, Ex vivo expansion of human mesenchymal stem cells in defined serum-free media, Stem Cell. Int., 2012, 123030 Baker, 2016, Reproducibility: respect your cells!, Nature, 537, 433, 10.1038/537433a Brennan, 2014, Pre-clinical studies of bone regeneration with human bone marrow stromal cells and biphasic calcium phosphate, Stem Cell Res. Ther., 5, 114, 10.1186/scrt504 Eyckmans, 2010, A clinically relevant model of osteoinduction: a process requiring calcium phosphate and BMP/Wnt signalling, J. Cell Mol. Med., 14, 1845, 10.1111/j.1582-4934.2009.00807.x Gamblin, 2014, Bone tissue formation with human mesenchymal stem cells and biphasic calcium phosphate ceramics: the local implication of osteoclasts and macrophages, Biomaterials, 35, 9660, 10.1016/j.biomaterials.2014.08.018 Mendicino, 2014, MSC-based product characterization for clinical trials: an FDA perspective, Cell Stem cell, 14, 141, 10.1016/j.stem.2014.01.013 Agency EM, 1998 Agency EM, 2008 Dominici, 2006, Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement, Cytotherapy, 8, 315, 10.1080/14653240600855905 Bara, 2014, Concise review: bone marrow-derived mesenchymal stem cells change phenotype following in vitro culture: implications for basic research and the clinic, Stem Cell., 32, 1713, 10.1002/stem.1649 Billing, 2016, Comprehensive transcriptomic and proteomic characterization of human mesenchymal stem cells reveals source specific cellular markers, Sci. Rep., 6, 21507, 10.1038/srep21507 Deveza, 2018, Comparative analysis of gene expression identifies distinct molecular signatures of bone marrow- and periosteal-skeletal stem/progenitor cells, PLoS One, 13, e0190909, 10.1371/journal.pone.0190909 Chan, 2015, Identification and specification of the mouse skeletal stem cell, Cell, 160, 285, 10.1016/j.cell.2014.12.002 Doi, 1994, Vascularized periosteal bone graft from the supracondylar region of the femur, Microsurgery, 15, 305, 10.1002/micr.1920150505 Schmelzeisen, 2003, Making bone: implant insertion into tissue-engineered bone for maxillary sinus floor augmentation-a preliminary report, J. Craniomaxillofacial Surg., 31, 34, 10.1016/S1010-5182(02)00163-4 Wagner, 2008, Replicative senescence of mesenchymal stem cells: a continuous and organized process, PLoS One, 3, e2213, 10.1371/journal.pone.0002213 Roseti, 2017, Scaffolds for bone tissue engineering: state of the art and new perspectives, Mater. Sci. Eng. C Mater. Biol. Appl., 78, 1246, 10.1016/j.msec.2017.05.017 Tang, 2016, Biofabrication of bone tissue: approaches, challenges and translation for bone regeneration, Biomaterials, 83, 363, 10.1016/j.biomaterials.2016.01.024 Li, 2016, Recent advances in bioprinting techniques: approaches, applications and future prospects, J. Transl. Med., 14, 271, 10.1186/s12967-016-1028-0 Aljohani, 2018, Bioprinting and its applications in tissue engineering and regenerative medicine, Int. J. Biol. Macromol., 107, 261, 10.1016/j.ijbiomac.2017.08.171 Adepu, 2017, Three-dimensional bioprinting for bone tissue regeneration, Curr. Opin. Biomed. Eng., 2, 22, 10.1016/j.cobme.2017.03.005 Lin, 2016, Low-temperature additive manufacturing of biomimic three-dimensional hydroxyapatite/collagen scaffolds for bone regeneration, ACS Appl. Mater. Interfaces, 8, 6905, 10.1021/acsami.6b00815 Park, 2015, 3D printing technology to control BMP-2 and VEGF delivery spatially and temporally to promote large-volume bone regeneration, J. Mater. Chem. B, 3, 5415, 10.1039/C5TB00637F Ratheesh, 2017, 3D fabrication of polymeric scaffolds for regenerative therapy, ACS Biomater. Sci. Eng., 3, 1175, 10.1021/acsbiomaterials.6b00370 Liu, 2011, Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-gamma and TNF-alpha, Nat. Med., 17, 1594, 10.1038/nm.2542 Martino, 2015, Extracellular matrix-inspired growth factor delivery systems for bone regeneration, Adv. Drug Deliv. Rev., 94, 41, 10.1016/j.addr.2015.04.007 Mani, 2007, Coronary stents: a materials perspective, Biomaterials, 28, 1689, 10.1016/j.biomaterials.2006.11.042 Takahashi, 2007, Induction of pluripotent stem cells from adult human fibroblasts by defined factors, Cell, 131, 861, 10.1016/j.cell.2007.11.019 Tsumaki, 2015, iPS cell technologies and cartilage regeneration, Bone, 70, 48, 10.1016/j.bone.2014.07.011 Krell, 2016, The efficacy of platelet-derived growth factor as a bone-stimulating agent, Foot Ankle Clin., 21, 763, 10.1016/j.fcl.2016.07.002 Simank, 2001, Bone morphogenetic protein-2 and growth and differentiation factor-5 enhance the healing of necrotic bone in a sheep model, Growth Factors, 19, 247, 10.3109/08977190109001090 Kasten, 2010, The effect of two point mutations in GDF-5 on ectopic bone formation in a beta-tricalciumphosphate scaffold, Biomaterials, 31, 3878, 10.1016/j.biomaterials.2010.01.109 Lin, 2012, B2A peptide induces chondrogenic differentiation in vitro and enhances cartilage repair in rats, J. Orthop. Res., 30, 1221, 10.1002/jor.22078 Yukna, 1998, Multi-center clinical evaluation of combination anorganic bovine-derived hydroxyapatite matrix (ABM)/cell binding peptide (P-15) as a bone replacement graft material in human periodontal osseous defects. 6-month results, J. Periodontol., 69, 655, 10.1902/jop.1998.69.6.655