Animals; Bone and Bones; Computer Simulation; Humans; Prostheses and Implants; Tissue Engineering; Automation; Biofabrication; Biomanufacturing; Clinical translation; Endochondral ossification; In silico tools; Omics; Scale-up; Tissue engineering
Résumé :
[en] A decade after the term developmental engineering (DE) was coined to indicate the use of developmental processes as blueprints for the design and development of engineered living implants, a myriad of proof-of-concept studies demonstrate the potential of this approach in small animal models. This review provides an overview of DE work, focusing on applications in bone regeneration. Enabling technologies allow to quantify the distance between in vitro processes and their developmental counterpart, as well as to design strategies to reduce that distance. By embedding Nature's robust mechanisms of action in engineered constructs, predictive large animal data and subsequent positive clinical outcomes can be gradually achieved. To this end, the development of next generation biofabrication technologies should provide the necessary scale and precision for robust living bone implant biomanufacturing.
Disciplines :
Ingénierie, informatique & technologie: Multidisciplinaire, généralités & autres
Auteur, co-auteur :
Papantoniou, Ioannis; Institute of Chemical Engineering Sciences, Foundation for Research and
Nilsson Hall, Gabriella; Skeletal Biology & Engineering Research Center, KU Leuven, Herestraat 49 (813),
Loverdou, Niki ; Université de Liège - ULiège > GIGA ; Prometheus, The KU Leuven R&D Division for Skeletal Tissue Engineering,
Lesage, Raphaelle; Prometheus, The KU Leuven R&D Division for Skeletal Tissue Engineering,
Herpelinck, Tim; Skeletal Biology & Engineering Research Center, KU Leuven, Herestraat 49 (813),
Mendes, Luis; Skeletal Biology & Engineering Research Center, KU Leuven, Herestraat 49 (813),
Geris, Liesbet ; Université de Liège - ULiège > GIGA > GIGA In silico medecine - Biomechanics Research Unit ; Skeletal Biology & Engineering Research Center, KU Leuven, Herestraat 49 (813),
Langue du document :
Anglais
Titre :
Turning Nature's own processes into design strategies for living bone implant biomanufacturing: a decade of Developmental Engineering.
Geris, L., Papantoniou, I., The third era of tissue engineering: reversing the innovation drivers. Tissue Eng. - Part A. 25 (2019), 821–826, 10.1089/ten.tea.2019.0064.
Lenas, P., Moos, M.J., Luyten, F.P., 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. - Part B Rev. 15 (2009), 381–394, 10.1089/ten.TEB.2008.0575.
Lenas, P., Moos, M., Luyten, F.P., 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. - Part B, Rev. 15 (2009), 395–422, 10.1089/ten.TEB.2009.0461.
Martin, I., Engineered tissues as customized organ germs. Tissue Eng. - Part A. 20 (2014), 1132–1133, 10.1089/ten.tea.2013.0772.
Marcucio, R.S., Qin, L., Alsberg, E., Boerckel, J.D., Reverse engineering development: Crosstalk opportunities between developmental biology and tissue engineering. J. Orthop. Res. 35 (2017), 2356–2368, 10.1002/jor.23636.
Freeman, F.E., McNamara, L.M., Endochondral priming: a developmental engineering strategy for bone tissue regeneration. Tissue Eng. - Part B Rev. 23 (2017), 128–141, 10.1089/ten.teb.2016.0197.
Kronenberg, H.M., Developmental regulation of the growth plate. Nature. 423 (2003), 332–336, 10.1038/nature01657.
Vortkamp, A., Pathi, S., Peretti, G.M., Caruso, E.M., Zaleske, D.J., Tabin, C.J., Recapitulation of signals regulating embryonic bone formation during postnatal growth and in fracture repair. Mech. Dev. 71 (1998), 65–76, 10.1016/S0925-4773(97)00203-7.
Lenas, P., Luyten, F.P., An Emerging Paradigm in Tissue Engineering: From Chemical Engineering to Developmental Engineering for Bioartificial Tissue Formation through a Series of Unit Operations that Simulate the In vivo Successive Developmental Stages. Ind. Eng. Chem. Res. 50 (2011), 482–522, 10.1021/ie100314b.
Ingber, D.E., Mow, V.C., Butler, D., Niklason, L., Huard, J., Mao, J., Yannas, I., Kaplan, D., Vunjak-Novakovic, G., Tissue engineering and developmental biology: Going biomimetic. Tissue Eng. 12 (2006), 3265–3283, 10.1089/ten.2006.12.3265.
Thompson, E.M., Matsiko, A., Farrell, E., Kelly, D.J., O'Brien, F.J., Recapitulating endochondral ossification: A promising route to in vivo bone regeneration. J. Tissue Eng. Regen. Med. 9 (2015), 889–902, 10.1002/term.1918.
Nilsson Hall, G., Mendes, L.F., Gklava, C., Geris, L., Luyten, F.P., Papantoniou, I., Developmentally Engineered Callus Organoid Bioassemblies Exhibit Predictive In vivo Long Bone Healing. Adv. Sci., 7, 2020, 1902295, 10.1002/advs.201902295.
Herberg, S., McDermott, A.M., Dang, P.N., Alt, D.S., Tang, R., Dawahare, J.H., Varghai, D., Shin, J.Y., McMillan, A., Dikina, A.D., He, F., Lee, Y.B., Cheng, Y., Umemori, K., Wong, P.C., Park, H., Boerckel, J.D., Alsberg, E., Combinatorial morphogenetic and mechanical cues to mimic bone development for defect repair. Sci. Adv., 5, 2019, eaax2476, 10.1126/sciadv.aax2476.
McDermott, A.M., Herberg, S., Mason, D.E., Collins, J.M., Pearson, H.B., Dawahare, J.H., Tang, R., Patwa, A.N., Grinstaff, M.W., Kelly, D.J., Alsberg, E., Boerckel, J.D., Recapitulating bone development through engineered mesenchymal condensations and mechanical cues for tissue regeneration. Sci. Transl. Med., 11, 2019, 157362, 10.1126/scitranslmed.aav7756.
Oliveira, S.M., Mijares, D.Q., Turner, G., Amaral, I.F., Barbosa, M.A., Teixeira, C.C., Engineering endochondral bone: In vivo studies. Tissue Eng. - Part A. 15 (2009), 635–643, 10.1089/ten.tea.2008.0052.
Janicki, P., Kasten, P., Kleinschmidt, K., Luginbuehl, R., Richter, W., Chondrogenic pre-induction of human mesenchymal stem cells on β-TCP: Enhanced bone quality by endochondral heterotopic bone formation. Acta Biomater. 6 (2010), 3292–3301, 10.1016/j.actbio.2010.01.037.
Pelttari, K., Winter, A., Steck, E., Goetzke, K., Hennig, T., Ochs, B.G., Aigner, T., Richter, W., Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice. Arthritis Rheum. 54 (2006), 3254–3266, 10.1002/art.22136.
Farrell, E., Both, S.K., Odörfer, K.I., Koevoet, W., Kops, N., O'Brien, F.J., De Jong, R.J.B., Verhaar, J.A., Cuijpers, V., Jansen, J., Erben, R.G., Van Osch, G.J.V.M., In-vivo generation of bone via endochondral ossification by in-vitro chondrogenic priming of adult human and rat mesenchymal stem cells. BMC Musculoskelet. Disord., 12, 2011, 31, 10.1186/1471-2474-12-31.
Liu, Y., Kuang, B., Rothrauff, B.B., Tuan, R.S., Lin, H., Robust bone regeneration through endochondral ossification of human mesenchymal stem cells within their own extracellular matrix. Biomaterials., 218, 2019, 119336, 10.1016/j.biomaterials.2019.119336.
Scotti, C., Tonnarelli, B., Papadimitropoulos, A., Scherberich, A., Schaeren, S., Schauerte, A., Lopez-Rios, J., Zeller, R., Barbero, A., Martin, I., Recapitulation of endochondral bone formation using human adult mesenchymal stem cells as a paradigm for developmental engineering. Proc. Natl. Acad. Sci. U. S. A. 107 (2010), 7251–7256, 10.1073/pnas.1000302107.
Serafini, M., Sacchetti, B., Pievani, A., Redaelli, D., Remoli, C., Biondi, A., Riminucci, M., Bianco, P., Establishment of bone marrow and hematopoietic niches in vivo by reversion of chondrocyte differentiation of human bone marrow stromal cells. Stem Cell Res. 12 (2014), 659–672, 10.1016/j.scr.2014.01.006.
Todorov, A., Scotti, C., Barbero, A., Scherberich, A., Papadimitropoulos, A., Martin, I., Monocytes seeded on engineered hypertrophic cartilage do not enhance endochondral ossification capacity. Tissue Eng. - Part A. 23 (2017), 708–715, 10.1089/ten.tea.2016.0553.
Mendes, L.F., Katagiri, H., Tam, W.L., Chai, Y.C., Geris, L., Roberts, S.J., Luyten, F.P., Advancing osteochondral tissue engineering: Bone morphogenetic protein, transforming growth factor, and fibroblast growth factor signaling drive ordered differentiation of periosteal cells resulting in stable cartilage and bone formation in vivo. Stem Cell Res. Ther. 9 (2018), 1–13, 10.1186/s13287-018-0787-3.
Weiss, H.E., Roberts, S.J., Schrooten, J., Luyten, F.P., A semi-autonomous model of endochondral ossification for developmental tissue engineering. Tissue Eng. Part A. 18 (2012), 1334–1343, 10.1089/ten.tea.2011.0602.
Daly, A.C., Cunniffe, G.M., Sathy, B.N., Jeon, O., Alsberg, E., Kelly, D.J., 3D Bioprinting of Developmentally Inspired Templates for Whole Bone Organ Engineering, Adv. Healthc. Mater. 5 (2016), 2353–2362, 10.1002/adhm.201600182.
Daly, A.C., Pitacco, P., Nulty, J., Cunniffe, G.M., Kelly, D.J., 3D printed microchannel networks to direct vascularisation during endochondral bone repair. Biomaterials. 162 (2018), 34–46, 10.1016/j.biomaterials.2018.01.057.
Dennis, S.C., Berkland, C.J., Bonewald, L.F., Detamore, M.S., Endochondral Ossification for Enhancing Bone Regeneration: Converging Native Extracellular Matrix Biomaterials and Developmental Engineering in vivo. Tissue Eng. - Part B Rev. 21 (2015), 247–266, 10.1089/ten.teb.2014.0419.
Baptista, L.S., Kronemberger, G.S., Côrtes, I., Charelli, L.E., Matsui, R.A.M., Palhares, T.N., Sohier, J., Rossi, A.M., Granjeiro, J.M., Adult stem cells spheroids to optimize cell colonization in scaffolds for cartilage and bone tissue engineering. Int. J. Mol. Sci. 19 (2018), 1969–1986, 10.3390/ijms19051285.
Kruijt Spanjer, E.C., Bittermann, G.K.P., van Hooijdonk, I.E.M., Rosenberg, A.J.W.P., Gawlitta, D., Taking the endochondral route to craniomaxillofacial bone regeneration: A logical approach?. J. Cranio-Maxillofacial Surg. 45 (2017), 1099–1106, 10.1016/j.jcms.2017.03.025.
Sheehy, E.J., Kelly, D.J., O'Brien, F.J., Biomaterial-based endochondral bone regeneration: a shift from traditional tissue engineering paradigms to developmentally inspired strategies. Mater. Today Bio., 3, 2019, 100009, 10.1016/j.mtbio.2019.100009.
Lienemann, P.S., Lutolf, M.P., Ehrbar, M., Biomimetic hydrogels for controlled biomolecule delivery to augment bone regeneration. Adv. Drug Deliv. Rev. 64 (2012), 1078–1089, 10.1016/j.addr.2012.03.010.
Gjorevski, N., Ranga, A., Lutolf, M.P., Bioengineering approaches to guide stem cell-based organogenesis. Dev. 141 (2014), 1794–1804, 10.1242/dev.101048.
Goodwin, S., McPherson, J.D., McCombie, W.R., Coming of age: Ten years of next-generation sequencing technologies. Nat. Rev. Genet. 17 (2016), 333–351, 10.1038/nrg.2016.49.
Lowe, R., Shirley, N., Bleackley, M., Dolan, S., Shafee, T., Transcriptomics technologies. PLoS Comput. Biol., 13, 2017, 10.1371/journal.pcbi.1005457.
Svensson, V., Vento-Tormo, R., Teichmann, S.A., Exponential scaling of single-cell RNA-seq in the past decade. Nat. Protoc., 13, 2018, 599, 10.1038/nprot.2017.149.
Cao, J., Spielmann, M., Qiu, X., Huang, X., Ibrahim, D.M., Hill, A.J., Zhang, F., Mundlos, S., Christiansen, L., Steemers, F.J., Trapnell, C., Shendure, J., The single-cell transcriptional landscape of mammalian organogenesis. Nature. 566 (2019), 496–502, 10.1038/s41586-019-0969-x.
Schaum, N., Karkanias, J., Neff, N.F., May, A.P., Quake, S.R., Wyss-Coray, T., Darmanis, S., Batson, J., Botvinnik, O., Chen, M.B., Chen, S., Green, F., Jones, R.C., Maynard, A., Penland, L., Pisco, A.O., Sit, R.V., Stanley, G.M., Webber, J.T., Zanini, F., Baghel, A.S., Bakerman, I., Bansal, I., Berdnik, D., Bilen, B., Brownfield, D., Cain, C., Cho, M., Cirolia, G., Conley, S.D., Demers, A., Demir, K., de Morree, A., Divita, T., du Bois, H., Dulgeroff, L.B.T., Ebadi, H., Espinoza, F.H., Fish, M., Gan, Q., George, B.M., Gillich, A., Genetiano, G., Gu, X., Gulati, G.S., Hang, Y., Hosseinzadeh, S., Huang, A., Iram, T., Isobe, T., Ives, F., Kao, K.S., Karnam, G., Kershner, A.M., Kiss, B.M., Kong, W., Kumar, M.E., Lam, J.Y., Lee, D.P., Lee, S.E., Li, G., Li, Q., Liu, L., Lo, A., Lu, W.J., Manjunath, A., May, K.L., May, O.L., McKay, M., Metzger, R.J., Mignardi, M., Min, D., Nabhan, A.N., Ng, K.M., Noh, J., Patkar, R., Peng, W.C., Puccinelli, R., Rulifson, E.J., Sikandar, S.S., Sinha, R., Szade, K., Tan, W., Tato, C., Tellez, K., Travaglini, K.J., Tropini, C., Waldburger, L., van Weele, L.J., Wosczyna, M.N., Xiang, J., Xue, S., Youngyunpipatkul, J., Zardeneta, M.E., Zhang, F., Zhou, L., Castro, P., Croote, D., DeRisi, J.L., Kuo, C.S., Lehallier, B., Nguyen, P.K., Tan, S.Y., Wang, B.M., Yousef, H., Beachy, P.A., Chan, C.K.F., Huang, K.C., Weinberg, K., Wu, M., Barres, B.A., Clarke, M.F., Kim, S.K., Krasnow, M.A., Nusse, R., Rando, T.A., Sonnenburg, J., Weissman, I.L., Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris. Nature. 562 (2018), 367–372, 10.1038/s41586-018-0590-4.
Wagner, D.E., Weinreb, C., Collins, Z.M., Briggs, J.A., Megason, S.G., Klein, A.M., Single-cell mapping of gene expression landscapes and lineage in the zebrafish embryo. Science. 360 (2018), 981–987, 10.1126/science.aar4362.
Karaiskos, N., Wahle, P., Alles, J., Boltengagen, A., Ayoub, S., Kipar, C., Kocks, C., Rajewsky, N., Zinzen, R.P., The Drosophila embryo at single-cell transcriptome resolution. Science. 358 (2017), 194–199, 10.1126/science.aan3235.
Briggs, J.A., Weinreb, C., Wagner, D.E., Megason, S., Peshkin, L., Kirschner, M.W., Klein, A.M., The dynamics of gene expression in vertebrate embryogenesis at single-cell resolution. Science, 360, 2018, eaar5780, 10.1126/science.aar5780.
La Manno, G., Gyllborg, D., Codeluppi, S., Nishimura, K., Salto, C., Zeisel, A., Borm, L.E., Stott, S.R.W., Toledo, E.M., Villaescusa, J.C., Lönnerberg, P., Ryge, J., Barker, R.A., Arenas, E., Linnarsson, S., Molecular diversity of midbrain development in mouse, human, and stem cells. Cell, 167, 2016, 10.1016/j.cell.2016.09.027 566-580.e19.
Cellular, Tissue and Gene Therapies Advisory Committee May 8, 2020 Meeting Announcement - 05/08/2020 - 05/08/2020, 2020, FDA https://www.fda.gov/advisory-committees/advisory-committee-calendar/cellular-tissue-and-gene-therapies-advisory-committee-may-8-2020-meeting-announcement-05082020 (accessed September 11, 2020).
Camp, J.G., Wollny, D., Treutlein, B., Single-cell genomics to guide human stem cell and tissue engineering. Nat. Methods. 15 (2018), 661–667, 10.1038/s41592-018-0113-0.
Subramanian, A., Sidhom, E.H., Emani, M., Vernon, K., Sahakian, N., Zhou, Y., Kost-Alimova, M., Slyper, M., Waldman, J., Dionne, D., Nguyen, L.T., Weins, A., Marshall, J.L., Rosenblatt-Rosen, O., Regev, A., Greka, A., Single cell census of human kidney organoids shows reproducibility and diminished off-target cells after transplantation. Nat. Commun. 10 (2019), 1–15, 10.1038/s41467-019-13382-0.
Lukovic, D., Artero Castro, A., Kaya, K.D., Munezero, D., Gieser, L., Davó-Martínez, C., Corton, M., Cuenca, N., Swaroop, A., Ramamurthy, V., Ayuso, C., Erceg, S., Retinal Organoids derived from hiPSCs of an AIPL1-LCA Patient Maintain Cytoarchitecture despite Reduced levels of Mutant AIPL1. Sci. Rep. 10 (2020), 1–13, 10.1038/s41598-020-62047-2.
Camp, J.G., Badsha, F., Florio, M., Kanton, S., Gerber, T., Wilsch-Bräuninger, M., Lewitus, E., Sykes, A., Hevers, W., Lancaster, M., Knoblich, J.A., Lachmann, R., Pääbo, S., Huttner, W.B., Treutlein, B., Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Proc. Natl. Acad. Sci. U. S. A. 112 (2015), 15672–15677, 10.1073/pnas.1520760112.
Kanton, S., Boyle, M.J., He, Z., Santel, M., Weigert, A., Sanchís-Calleja, F., Guijarro, P., Sidow, L., Fleck, J.S., Han, D., Qian, Z., Heide, M., Huttner, W.B., Khaitovich, P., Pääbo, S., Treutlein, B., Camp, J.G., Organoid single-cell genomic atlas uncovers human-specific features of brain development. Nature. 574 (2019), 418–422, 10.1038/s41586-019-1654-9.
Luo, C., Lancaster, M.A., Castanon, R., Nery, J.R., Knoblich, J.A., Ecker, J.R., Cerebral organoids recapitulate epigenomic signatures of the human fetal brain. Cell Rep. 17 (2016), 3369–3384, 10.1016/j.celrep.2016.12.001.
Tanaka, Y., Cakir, B., Xiang, Y., Sullivan, G.J., Park, I.H., Synthetic analyses of single-cell transcriptomes from multiple brain organoids and fetal brain. Cell Rep., 30, 2020, 10.1016/j.celrep.2020.01.038 1682-1689.e3.
Camp, J.G., Sekine, K., Gerber, T., Loeffler-Wirth, H., Binder, H., Gac, M., Kanton, S., Kageyama, J., Damm, G., Seehofer, D., Belicova, L., Bickle, M., Barsacchi, R., Okuda, R., Yoshizawa, E., Kimura, M., Ayabe, H., Taniguchi, H., Takebe, T., Treutlein, B., Multilineage communication regulates human liver bud development from pluripotency. Nature. 546 (2017), 533–538, 10.1038/nature22796.
Wang, D., Wang, J., Bai, L., Pan, H., Feng, H., Clevers, H., Zeng, Y.A., Long-Term Expansion of Pancreatic Islet Organoids from Resident Procr+ Progenitors. Cell, 180, 2020, 10.1016/j.cell.2020.02.048 1198-1211.e19.
Cacchiarelli, D., Qiu, X., Srivatsan, S., Manfredi, A., Ziller, M., Overbey, E., Grimaldi, A., Grimsby, J., Pokharel, P., Livak, K.J., Li, S., Meissner, A., Mikkelsen, T.S., Rinn, J.L., Trapnell, C., Aligning single-cell developmental and reprogramming trajectories identifies molecular determinants of myogenic reprogramming outcome. Cell Syst., 7, 2018, 10.1016/j.cels.2018.07.006 258-268.e3.
Feregrino, C., Sacher, F., Parnas, O., Tschopp, P., A single-cell transcriptomic atlas of the developing chicken limb. BMC Genomics., 20, 2019, 401, 10.1186/s12864-019-5802-2.
Kelly, N.H., Huynh, N.P.T., Guilak, F., Single cell RNA-sequencing reveals cellular heterogeneity and trajectories of lineage specification during murine embryonic limb development. Matrix Biol. 89 (2020), 1–10, 10.1016/j.matbio.2019.12.004.
Bian, Q., Cheng, Y.H., Wilson, J.P., Su, E.Y., Kim, D.W., Wang, H., Yoo, S., Blackshaw, S., Cahan, P., A single cell transcriptional atlas of early synovial joint development. Development, 147, 2020, 10.1242/dev.185777.
Efremova, M., Vento-Tormo, M., Teichmann, S.A., Vento-Tormo, R., CellPhoneDB: inferring cell–cell communication from combined expression of multi-subunit ligand–receptor complexes. Nat. Protoc. 15 (2020), 1484–1506, 10.1038/s41596-020-0292-x.
Cabello-Aguilar, S., Alame, M., Kon-Sun-Tack, F., Fau, C., Lacroix, M., Colinge, J., SingleCellSignalR: inference of intercellular networks from single-cell transcriptomics. Nucleic Acids Res., 48, 2020, e55, 10.1093/nar/gkaa183.
Wang, Y., Wang, R., Zhang, S., Song, S., Jiang, C., Han, G., Wang, M., Ajani, J., Futreal, A., Wang, L., iTALK: an R Package to characterize and illustrate intercellular communication. BioRxiv, 2019, 10.1101/507871.
Scadden, D.T., The stem-cell niche as an entity of action. Nature. 441 (2006), 1075–1079, 10.1038/nature04957.
Chan, C.K.F., Seo, E.Y., Chen, J.Y., Lo, D., McArdle, A., Sinha, R., Tevlin, R., Seita, J., Vincent-Tompkins, J., Wearda, T., Lu, W.J., Senarath-Yapa, K., Chung, M.T., Marecic, O., Tran, M., Yan, K.S., Upton, R., Walmsley, G.G., Lee, A.S., Sahoo, D., Kuo, C.J., Weissman, I.L., Longaker, M.T., Identification and specification of the mouse skeletal stem cell. Cell. 160 (2015), 285–298, 10.1016/j.cell.2014.12.002.
Debnath, S., Yallowitz, A.R., McCormick, J., Lalani, S., Zhang, T., Xu, R., Li, N., Liu, Y., Yang, Y.S., Eiseman, M., Shim, J.H., Hameed, M., Healey, J.H., Bostrom, M.P., Landau, D.A., Greenblatt, M.B., Discovery of a periosteal stem cell mediating intramembranous bone formation. Nature. 562 (2018), 133–139, 10.1038/s41586-018-0554-8.
Chan, C.K.F., Gulati, G.S., Sinha, R., Tompkins, J.V., Lopez, M., Carter, A.C., Ransom, R.C., Reinisch, A., Wearda, T., Murphy, M., Brewer, R.E., Koepke, L.S., Marecic, O., Manjunath, A., Seo, E.Y., Leavitt, T., Lu, W.-J., Nguyen, A., Conley, S.D., Salhotra, A., Ambrosi, T.H., Borrelli, M.R., Siebel, T., Chan, K., Schallmoser, K., Seita, J., Sahoo, D., Goodnough, H., Bishop, J., Gardner, M., Majeti, R., Wan, D.C., Goodman, S., Weissman, I.L., Chang, H.Y., Longaker, M.T., Identification of the human skeletal stem cell. Cell, 175, 2018, 10.1016/j.cell.2018.07.029 43-56.e21.
Medaglia, C., Giladi, A., Stoler-Barak, L., De Giovanni, M., Salame, T.M., Biram, A., David, E., Li, H., Iannacone, M., Shulman, Z., Amit, I., Spatial reconstruction of immune niches by combining photoactivatable reporters and scRNA-seq. Science. 358 (2017), 1622–1626, 10.1126/science.aao4277.
Rodriques, S.G., Stickels, R.R., Goeva, A., Martin, C.A., Murray, E., Vanderburg, C.R., Welch, J., Chen, L.M., Chen, F., Macosko, E.Z., Slide-seq: A scalable technology for measuring genome-wide expression at high spatial resolution. Science. 363 (2019), 1463–1467, 10.1126/science.aaw1219.
Lubeck, E., Coskun, A.F., Zhiyentayev, T., Ahmad, M., Cai, L., Single-cell in situ RNA profiling by sequential hybridization. Nat. Methods. 11 (2014), 360–361, 10.1038/nmeth.2892.
Baccin, C., Al-Sabah, J., Velten, L., Helbling, P.M., Grünschläger, F., Hernández-Malmierca, P., Nombela-Arrieta, C., Steinmetz, L.M., Trumpp, A., Haas, S., Combined single-cell and spatial transcriptomics reveal the molecular, cellular and spatial bone marrow niche organization. Nat. Cell Biol. 22 (2020), 38–48, 10.1038/s41556-019-0439-6.
Mueller, A.J., Tew, S.R., Vasieva, O., Clegg, P.D., Canty-Laird, E.G., A systems biology approach to defining regulatory mechanisms for cartilage and tendon cell phenotypes. Sci. Rep. 6 (2016), 1–14, 10.1038/srep33956.
Lenas, P., Luyten, F.P., Doblare, M., Nicodemou-Lena, E., Lanzara, A.E., Modularity in developmental biology and artificial organs: A missing concept in tissue engineering. Artif. Organs. 35 (2011), 656–662, 10.1111/j.1525-1594.2010.01135.x.
Le Novère, N., Quantitative and logic modelling of molecular and gene networks. Nat. Rev. Genet. 16 (2015), 146–158, 10.1038/nrg3885.
Lesage, R., Kerkhofs, J., Geris, L.G., Computational modeling and reverse engineering to reveal dominant regulatory interactions controlling osteochondral differentiation: potential for regenerative medicine, Front. Bioeng. Biotechnol., 6, 2018, 165, 10.3389/FBIOE.2018.00165.
Pir, P., Le Novère, N., Mathematical models of pluripotent stem cells: At the dawn of predictive regenerative medicine. Methods Mol. Biol. 1386 (2016), 331–350, 10.1007/978-1-4939-3283-2_15.
Kauffman, S., Homeostasis and differentiation in random genetic control networks. Nature. 224 (1969), 177–178, 10.1038/224177a0.
Kauffman, S.A., The origins of order: self organization and selection in evolution. 1994, Oxford University Press, 10.1016/0020-711X(94)90119-8.
Kerkhofs, J., Leijten, J., Bolander, J., Luyten, F.P., Post, J.N., Geris, L., A qualitative model of the differentiation network in chondrocyte maturation: A holistic view of chondrocyte hypertrophy. PLoS One. 11 (2016), 1–27, 10.1371/journal.pone.0162052.
Montagud, A., Traynard, P., Martignetti, L., Bonnet, E., Barillot, E., Zinovyev, A., Calzone, L., Conceptual and computational framework for logical modelling of biological networks deregulated in diseases. Brief. Bioinform. 20 (2018), 1238–1249, 10.1093/bib/bbx163.
Kerkhofs, J., Geris, L., A semiquantitative framework for gene regulatory networks: increasing the time and quantitative resolution of boolean networks. PLoS One., 10, 2015, e0130033, 10.1371/journal.pone.0130033.
Albert, R., Othmer, H.G., The topology of the regulatory interactions predicts the expression pattern of the segment polarity genes in Drosophila melanogaster. J. Theor. Biol. 223 (2003), 1–18, 10.1016/S0022-5193(03)00035-3.
Michael Verdicchio, K. Seungchan, Identifying targets for intervention by analyzing basins of attraction. Pac. Symp. Biocomput., 2011, 350–361.
Michael Verdicchio, K., Seungchan, Template-based intervention in Boolean network models of biological systems. EURASIP J. Bioinforma. Syst. Biol., 2014, 2014, 11, 10.1186/s13637-014-0011-4.
Barabási, A.L., Scale-free networks: A decade and beyond. Science. 325 (2009), 412–413, 10.1126/science.1173299.
Gao, J., Liu, Y.Y., D'Souza, R.M., Barabási, A.L., Target control of complex networks. Nat. Commun. 5 (2014), 1–8, 10.1038/ncomms6415.
Kobayashi, K., Maeda, K., Tokuoka, M., Mochizuki, A., Satou, Y., Controlling cell fate specification system by key genes determined from network structure. IScience. 4 (2018), 281–293, 10.1016/j.isci.2018.05.004.
Letort, G., Montagud, A., Stoll, G., Heiland, R., Barillot, E., MacKlin, P., Zinovyev, A., Calzone, L., PhysiBoSS: A multi-scale agent-based modelling framework integrating physical dimension and cell signalling. Bioinformatics. 35 (2019), 1188–1196, 10.1093/bioinformatics/bty766.
Swat, M.H., Thomas, G.L., Belmonte, J.M., Shirinifard, A., Hmeljak, D., Glazier, J.A., Multi-Scale Modeling of Tissues Using CompuCell3D. Methods Cell Biol., Academic Press Inc, 2012, 325–366, 10.1016/B978-0-12-388403-9.00013-8.
Meir, E., Munro, E.M., Odell, G.M., Von Dassow, G., Ingeneue: A versatile tool for reconstituting genetic networks, with examples from the segment polarity network. J. Exp. Zool. 294 (2002), 216–251, 10.1002/jez.10187.
Tanaka, S., Sichau, D., Iber, D., LBIB Cell: A cell-based simulation environment for morphogenetic problems. Bioinformatics. 31 (2015), 2340–2347, 10.1093/bioinformatics/btv147.
Glimm, T., Headon, D., Kiskowski, M.A., Computational and mathematical models of chondrogenesis in vertebrate limbs. Birth Defects Res. Part C - Embryo Today Rev. 96 (2012), 176–192, 10.1002/bdrc.21014.
Balaskas, N., Ribeiro, A., Panovska, J., Dessaud, E., Sasai, N., Page, K.M., Briscoe, J., Ribes, V., Gene regulatory logic for reading the sonic hedgehog signaling gradient in the vertebrate neural tube. Cell. 148 (2012), 273–284, 10.1016/j.cell.2011.10.047.
Fasano, A., Herrero, M.A., López, J.M., Medina, E., On the dynamics of the growth plate in primary ossification. J. Theor. Biol. 265 (2010), 543–553, 10.1016/j.jtbi.2010.05.030.
Delile, J., Herrmann, M., Peyriéras, N., Doursat, R., A cell-based computational model of early embryogenesis coupling mechanical behaviour and gene regulation. Nat. Commun. 8 (2017), 1–10, 10.1038/ncomms13929.
Cahan, P., Li, H., Morris, S.A., Lummertz Da Rocha, E., Daley, G.Q., Collins, J.J., CellNet: Network biology applied to stem cell engineering. Cell. 158 (2014), 903–915, 10.1016/j.cell.2014.07.020.
Radley, A.H., Schwab, R.M., Tan, Y., Kim, J., Lo, E.K.W., Cahan, P., Assessment of engineered cells using CellNet and RNA-seq. Nat. Protoc. 12 (2017), 1089–1102, 10.1038/nprot.2017.022.
Child, C.M., The physiological significance of the cephalocaudal differential in vertebrate development. Anat. Rec. 31 (1925), 369–383, 10.1002/ar.1090310403.
Pollesello, P., de Bernard, B., Grandolfo, M., Paoletti, S., Vittur, F., Kvam, B.J., Energy state of chondrocytes assessed by 31P-NMR studies of preosseous cartilage. Biochem. Biophys. Res. Commun. 180 (1991), 216–222, 10.1016/S0006-291X(05)81279-3.
Loeffler, J., Duda, G.N., Sass, F.A., Dienelt, A., The metabolic microenvironment steers bone tissue regeneration. Trends Endocrinol. Metab. 29 (2018), 99–110, 10.1016/j.tem.2017.11.008.
van Gastel, N., Stegen, S., Eelen, G., Schoors, S., Carlier, A., Daniëls, V.W., Baryawno, N., Przybylski, D., Depypere, M., Stiers, P.J., Lambrechts, D., Van Looveren, R., Torrekens, S., Sharda, A., Agostinis, P., Lambrechts, D., Maes, F., Swinnen, J.V., Geris, L., Van Oosterwyck, H., Thienpont, B., Carmeliet, P., Scadden, D.T., Carmeliet, G., Lipid availability determines fate of skeletal progenitor cells via SOX9. Nature 579 (2020), 111–117, 10.1038/s41586-020-2050-1.
Moussavi-Harami, F., Duwayri, Y., Martin, J.A., Moussavi-Harami, F., Buckwalter, J.A., Oxygen effects on senescence in chondrocytes and mesenchymal stem cells: consequences for tissue engineering. Iowa Orthop. J. 24 (2004), 15–20.
dos Santos, F., Andrade, P.Z., Boura, J.S., Abecasis, M.M., da Silva, C.L., Cabral, J.M.S., Ex vivo expansion of human mesenchymal stem cells: A more effective cell proliferation kinetics and metabolism under hypoxia. J. Cell. Physiol. 223 (2009), 28–35, 10.1002/jcp.21987.
Ghani, Q.P., Wagner, S., Hussain, M.Z., Hunt, T.K., Role of ADP-ribosylation in wound repair. The contributions of Thomas K. Hunt, MD. Wound Repair Regen. 11 (2003), 439–444, 10.1046/j.1524-475X.2003.11608.x.
Roland, C.L., Arumugam, T., Deng, D., Liu, S.H., Philip, B., Gomez, S., Burns, W.R., Ramachandran, V., Wang, H., Cruz-Monserrate, Z., Logsdon, C.D., Cell surface lactate receptor GPR81 is crucial for cancer cell survival. Cancer Res. 74 (2014), 5301–5310, 10.1158/0008-5472.CAN-14-0319.
Hoque, R., Farooq, A., Ghani, A., Gorelick, F., Mehal, W.Z., Lactate reduces liver and pancreatic injury in toll-like receptor- and inflammasome-mediated inflammation via gpr81-mediated suppression of innate immunity. Gastroenterology. 146 (2014), 1763–1774, 10.1053/j.gastro.2014.03.014.
Yuan, X., Logan, T.M., Ma, T., Metabolism in human mesenchymal stromal cells: A missing link between HMSC biomanufacturing and therapy?. Front. Immunol. 10 (2019), 1–11, 10.3389/fimmu.2019.00977.
Datta, P., Linhardt, R.J., Sharfstein, S.T., An ’omics approach towards CHO cell engineering. Biotechnol. Bioeng. 110 (2013), 1255–1271, 10.1002/bit.24841.
Standke, S.J., Colby, D.H., Bensen, R.C., Burgett, A.W.G., Yang, Z., Mass spectrometry measurement of single suspended cells using a combined cell manipulation system and a single-probe device. Anal. Chem. 91 (2019), 1738–1742, 10.1021/acs.analchem.8b05774.
Duncan, K.D., Fyrestam, J., Lanekoff, I., Advances in mass spectrometry based single-cell metabolomics. Analyst. 144 (2019), 782–793, 10.1039/c8an01581c.
Hansen, R.L., Lee, Y.J., High-spatial resolution mass spectrometry imaging: toward single cell metabolomics in plant tissues. Chem. Rec. 18 (2018), 65–77, 10.1002/tcr.201700027.
Guillermier, C., Doherty, S.P., Whitney, A.G., Babaev, V.R., Linton, M.F., Steinhauser, M.L., Brown, J.D., Imaging mass spectrometry reveals heterogeneity of proliferation and metabolism in atherosclerosis. JCI Insight. 4 (2019), 1–10, 10.1172/jci.insight.128528.
Alexandrov, T., Spatial Metabolomics and Imaging Mass Spectrometry in the Age of Artificial Intelligence. Annu. Rev. Biomed. Data Sci. 3 (2020), 61–87, 10.1146/annurev-biodatasci-011420-031537.
Heathman, T.R., Nienow, A.W., McCall, M.J., Coopman, K., Kara, B., Hewitt, C.J., The translation of cell-based therapies: clinical landscape and manufacturing challenges. Regen Med. 10 (2015), 49–64, 10.2217/rme.14.73.
Harrison, R.P., Medcalf, N., Rafiq, Q.A., Cell therapy-processing economics: small-scale microfactories as a stepping stone toward large-scale macrofactories. Regen Med. 13 (2018), 159–173, 10.2217/rme-2017-0103.
Tan, Z., Niu, B., Tsang, K.Y., Melhado, I.G., Ohba, S., He, X., Huang, Y., Wang, C., McMahon, A.P., Jauch, R., Chan, D., Zhang, M.Q., Cheah, K.S.E., Synergistic co-regulation and competition by a SOX9-GLI-FOXA phasic transcriptional network coordinate chondrocyte differentiation transitions. PLoS Genet., 14, 2018, e1007346, 10.1371/journal.pgen.1007346.
Power, L.J., Fasolato, C., Barbero, A., Wendt, D.J., Wixmerten, A., Martin, I., Asnaghi, M.A., Sensing tissue engineered cartilage quality with Raman spectroscopy and statistical learning for the development of advanced characterization assays. Biosens. Bioelectron., 166, 2020, 10.1016/j.bios.2020.112467.
Abraham, E., Ahmadian, B.B., Holderness, K., Levinson, Y., McAfee, E., Platforms for manufacturing allogeneic, autologous and iPSC cell therapy products: an industry perspective. Adv Biochem Eng Biotechnol, 2017/05/24, Research and Technology, Lonza, Walkersville, MD, USA, 2017, 323–350, 10.1007/10_2017_14.
Lambrechts, T., Papantoniou, I., Viazzi, S., Bovy, T., Schrooten, J., Luyten, F.P., Aerts, J.M., Evaluation of a monitored multiplate bioreactor for large-scale expansion of human periosteum derived stem cells for bone tissue engineering applications. Biochem. Eng. J. 108 (2016), 58–68, 10.1016/j.bej.2015.07.015.
Lambrechts, T., Papantoniou, I., Rice, B., Schrooten, J., Luyten, F.P., Aerts, J.M., Large-scale progenitor cell expansion for multiple donors in a monitored hollow fibre bioreactor. Cytotherapy. 18 (2016), 1219–1233, 10.1016/j.jcyt.2016.05.013.
Mizukami, A., de Abreu Neto, M.S., Moreira, F., Fernandes-Platzgummer, A., Huang, Y.F., Milligan, W., Cabral, J.M.S., da Silva, C.L., Covas, D.T., Swiech, K., Fully-Closed, A., Automated hollow fiber bioreactor for clinical-grade manufacturing of human mesenchymal stem/stromal cells. Stem Cell Rev Rep. 14 (2018), 141–143, 10.1007/s12015-017-9787-4.
Gupta, P., Hall, G.N., Geris, L., Luyten, F.P., Papantoniou, I., Human platelet lysate improves bone forming potential of human progenitor cells expanded in microcarrier-based dynamic culture. Stem Cells Transl Med. 8 (2019), 810–821, 10.1002/sctm.18-0216.
Heathman, T.R., Stolzing, A., Fabian, C., Rafiq, Q.A., Coopman, K., Nienow, A.W., Kara, B., Hewitt, C.J., Scalability and process transfer of mesenchymal stromal cell production from monolayer to microcarrier culture using human platelet lysate. Cytotherapy. 18 (2016), 523–535, 10.1016/j.jcyt.2016.01.007.
de Sousa Pinto, D., Bandeiras, C., de Almeida Fuzeta, M., Rodrigues, C.A.V., Jung, S., Hashimura, Y., Tseng, R.J., Milligan, W., Lee, B., Ferreira, F.C., Lobato da Silva, C., Cabral, J.M.S., Scalable manufacturing of human mesenchymal stromal cells in the vertical-wheel bioreactor system: an experimental and economic approach. Biotechnol. J., 14, 2019, 1800716, 10.1002/biot.201800716.
Lembong, J., Kirian, R., Takacs, J.D., Olsen, T.R., Lock, L.T., Rowley, J.A., Ahsan, T., Bioreactor parameters for microcarrier-based human MSC expansion under xeno-free conditions in a vertical-wheel system. Bioeng. (Basel, Switzerland), 7, 2020, 10.3390/bioengineering7030073.
Timmins, N.E., Kiel, M., Günther, M., Heazlewood, C., Doran, M.R., Brooke, G., Atkinson, K., Closed system isolation and scalable expansion of human placental mesenchymal stem cells. Biotechnol. Bioeng. 109 (2012), 1817–1826, 10.1002/bit.24425.
Grein, T.A., Leber, J., Blumenstock, M., Petry, F., Weidner, T., Salzig, D., Czermak, P., Multiphase mixing characteristics in a microcarrier-based stirred tank bioreactor suitable for human mesenchymal stem cell expansion. Process Biochem. 51 (2016), 1109–1119, 10.1016/j.procbio.2016.05.010.
Heathman, T.R.J., Glyn, V.A.M., Picken, A., Rafiq, Q.A., Coopman, K., Nienow, A.W., Kara, B., Hewitt, C.J., Expansion, harvest and cryopreservation of human mesenchymal stem cells in a serum-free microcarrier process. Biotechnol. Bioeng. 112 (2015), 1696–1707, 10.1002/bit.25582.
Rafiq, Q.A., Coopman, K., Nienow, A.W., Hewitt, C.J., Systematic microcarrier screening and agitated culture conditions improves human mesenchymal stem cell yield in bioreactors. Biotechnol. J. 11 (2016), 473–486, 10.1002/biot.201400862.
Rafiq, Q.A., Brosnan, K.M., Coopman, K., Nienow, A.W., Hewitt, C.J., Culture of human mesenchymal stem cells on microcarriers in a 5 l stirred-tank bioreactor. Biotechnol. Lett. 35 (2013), 1233–1245, 10.1007/s10529-013-1211-9.
Gupta, P., Geris, L., Luyten, F.P., Papantoniou, I., An integrated bioprocess for the expansion and chondrogenic priming of human periosteum-derived progenitor cells in suspension bioreactors. Biotechnol. J., 13, 2018, 1700087, 10.1002/biot.201700087.
Bolander, J., Ji, W., Leijten, J., Teixeira, L.M., Bloemen, V., Lambrechts, D., Chaklader, M., Luyten, F.P., Healing of a large long-bone defect through serum-free in vitro priming of human periosteum-derived cells. Stem Cell Reports. 8 (2017), 758–772, 10.1016/j.stemcr.2017.01.005.
Bolander, J., Herpelinck, T., Chaklader, M., Gklava, C., Geris, L., Luyten, F.P., Single-cell characterization and metabolic profiling of in vitro cultured human skeletal progenitors with enhanced in vivo bone forming capacity. Stem Cells Transl. Med., 2019, 10.1002/sctm.19-0151 sctm.19-0151.
Worthley, D.L., Churchill, M., Compton, J.T., Tailor, Y., Rao, M., Si, Y., Levin, D., Schwartz, M.G., Uygur, A., Hayakawa, Y., Gross, S., Renz, B.W., Setlik, W., Martinez, A.N., Chen, X., Nizami, S., Lee, H.G., Kang, H.P., Caldwell, J.M., Asfaha, S., Westphalen, C.B., Graham, T., Jin, G., Nagar, K., Wang, H., Kheirbek, M.A., Kolhe, A., Carpenter, J., Glaire, M., Nair, A., Renders, S., Manieri, N., Muthupalani, S., Fox, J.G., Reichert, M., Giraud, A.S., Schwabe, R.F., Pradere, J.P., Walton, K., Prakash, A., Gumucio, D., Rustgi, A.K., Stappenbeck, T.S., Friedman, R.A., Gershon, M.D., Sims, P., Grikscheit, T., Lee, F.Y., Karsenty, G., Mukherjee, S., Wang, T.C., Gremlin 1 identifies a skeletal stem cell with bone, cartilage. and reticular stromal potential, Cell. 160 (2015), 269–284, 10.1016/j.cell.2014.11.042.
Chen, Y., Xu, H., Lin, G., Generation of iPSC-derived limb progenitor-like cells for stimulating phalange regeneration in the adult mouse. Cell Discov. 3 (2017), 1–14, 10.1038/celldisc.2017.46.
Mehesz, A.N., Brown, J., Hajdu, Z., Beaver, W., da Silva, J.V., Visconti, R.P., Markwald, R.R., Mironov, V., Scalable robotic biofabrication of tissue spheroids. Biofabrication, 3, 2011, 25002, 10.1088/1758-5082/3/2/025002.
Ungrin, M.D., Joshi, C., Nica, A., Bauwens, C., Zandstra, P.W., Reproducible, ultra high-throughput formation of multicellular organization from single cell suspension-derived human embryonic stem cell aggregates. PLoS One., 3, 2008, e1565, 10.1371/journal.pone.0001565.
Futrega, K., Palmer, J.S., Kinney, M., Lott, W.B., Ungrin, M.D., Zandstra, P.W., Doran, M.R., The microwell-mesh: A novel device and protocol for the high throughput manufacturing of cartilage microtissues. Biomaterials. 62 (2015), 1–12, 10.1016/j.biomaterials.2015.05.013.
Tsai, A.C., Liu, Y., Yuan, X., Chella, R., Ma, T., Aggregation kinetics of human mesenchymal stem cells under wave motion. Biotechnol J., 12, 2017, 1600448, 10.1002/biot.201600448.
Egger, D., Schwedhelm, I., Hansmann, J., Kasper, C., Hypoxic three-dimensional scaffold-free aggregate cultivation of mesenchymal stem cells in a stirred tank reactor. Bioeng, 4, 2017, 10.3390/bioengineering4020047.
Allen, L.M., Matyas, J., Ungrin, M., Hart, D.A., Sen, A., Serum-free culture of human mesenchymal stem cell aggregates in suspension bioreactors for tissue engineering applications. Stem Cells Int., 2019, 2019, 4607461, 10.1155/2019/4607461.
Borys, B.S., Roberts, E.L., Le, A., Kallos, M.S., Scale-up of embryonic stem cell aggregate stirred suspension bioreactor culture enabled by computational fluid dynamics modeling. Biochem. Eng. J. 133 (2018), 157–167, 10.1016/j.bej.2018.02.005.
Moroni, L., Boland, T., Burdick, J.A., De Maria, C., Derby, B., Forgacs, G., Groll, J., Li, Q., Malda, J., Mironov, V.A., Mota, C., Nakamura, M., Shu, W., Takeuchi, S., Woodfield, T.B.F., Xu, T., Yoo, J.J., Vozzi, G., Biofabrication: a guide to technology and terminology. Trends Biotechnol. 36 (2018), 384–402, 10.1016/j.tibtech.2017.10.015.
De Moor, L., Fernandez, S., Vercruysse, C., Tytgat, L., Asadian, M., De Geyter, N., Van Vlierberghe, S., Dubruel, P., Declercq, H., Hybrid bioprinting of chondrogenically induced human mesenchymal stem cell spheroids. Front. Bioeng. Biotechnol., 8, 2020, 10.3389/fbioe.2020.00484.
Bayoussef, Z., Dixon, J.E., Stolnik, S., Shakesheff, K.M., Aggregation promotes cell viability, proliferation, and differentiation in an in vitro model of injection cell therapy. J. Tissue Eng. Regen. Med. 6 (2012), 61–73, 10.1002/term.482.
Daly, A.C., Kelly, D.J., Biofabrication of spatially organised tissues by directing the growth of cellular spheroids within 3D printed polymeric microchambers. Biomaterials. 197 (2019), 194–206, 10.1016/j.biomaterials.2018.12.028.
Yu, Y., Moncal, K.K., Li, J., Peng, W., Rivero, I., Martin, J.A., Ozbolat, I.T., Three-dimensional bioprinting using self-assembling scalable scaffold-free “tissue strands” as a new bioink. Sci Rep., 6, 2016, 28714, 10.1038/srep28714.
Ayan, B., Heo, D.N., Zhang, Z., Dey, M., Povilianskas, A., Drapaca, C., Ozbolat, I.T., Aspiration-assisted bioprinting for precise positioning of biologics. Sci Adv., 6, 2020, eaaw5111, 10.1126/sciadv.aaw5111.
Skylar-Scott, M.A., Uzel, S.G.M., Nam, L.L., Ahrens, J.H., Truby, R.L., Damaraju, S., Lewis, J.A., Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels. Sci Adv., 5, 2019, eaaw2459, 10.1126/sciadv.aaw2459.
Mekhileri, N.V., Lim, K.S., Brown, G.C.J., Mutreja, I., Schon, B.S., Hooper, G.J., Woodfield, T.B.F., Automated 3D bioassembly of micro-tissues for biofabrication of hybrid tissue engineered constructs. Biofabrication 10 (2018), 1969–1986, 10.1088/1758-5090/aa9ef1.
Moldovan, L., Barnard, A., Gil, C.H., Lin, Y., Grant, M.B., Yoder, M.C., Prasain, N., Moldovan, N.I., iPSC-derived vascular cell spheroids as building blocks for scaffold-free biofabrication. Biotechnol. J., 12, 2017, 1700444, 10.1002/biot.201700444.
Daly, A.C., Sathy, B.N., Kelly, D.J., Engineering large cartilage tissues using dynamic bioreactor culture at defined oxygen conditions. J Tissue Eng., 9, 2018, 10.1177/2041731417753718 2041731417753718.
McMaster, R., Hoefner, C., Hrynevich, A., Blum, C., Wiesner, M., Wittmann, K., Dargaville, T.R., Bauer-Kreisel, P., Groll, J., Dalton, P.D., Blunk, T., Tailored melt electrowritten scaffolds for the generation of sheet-like tissue constructs from multicellular spheroids. Adv Heal. Mater., 8, 2019, e1801326, 10.1002/adhm.201801326.
Albro, M.B., Nims, R.J., Durney, K.M., Cigan, A.D., Shim, J.J., Vunjak-Novakovic, G., Hung, C.T., Ateshian, G.A., Heterogeneous engineered cartilage growth results from gradients of media-supplemented active TGF-β and is ameliorated by the alternative supplementation of latent TGF-β. Biomaterials. 77 (2016), 173–185, 10.1016/j.biomaterials.2015.10.018.
Sarem, M., Otto, O., Tanaka, S., Shastri, V.P., Cell number in mesenchymal stem cell aggregates dictates cell stiffness and chondrogenesis. Stem Cell Res. Ther. 10 (2019), 1–18, 10.1186/s13287-018-1103-y.
Murphy, K.C., Hung, B.P., Browne-Bourne, S., Zhou, D., Yeung, J., Genetos, D.C., Leach, J.K., Measurement of oxygen tension within mesenchymal stem cell spheroids. J. R. Soc. Interface., 14, 2017, 20160851, 10.1098/rsif.2016.0851.
Spitters, T.W.G.M., Stamatialis, D., Petit, A., De Leeuw, M.G.W., Karperien, M., In vitro evaluation of small molecule delivery into articular cartilage: effect of synovial clearance and compressive load. Assay Drug Dev. Technol. 17 (2019), 191–200, 10.1089/adt.2018.907.
Sheehy, E.J., Buckley, C.T., Kelly, D.J., Oxygen tension regulates the osteogenic, chondrogenic and endochondral phenotype of bone marrow derived mesenchymal stem cells. Biochem. Biophys. Res. Commun. 417 (2012), 305–310, 10.1016/j.bbrc.2011.11.105.
Leijten, J., Georgi, N., Teixeira, L.M., Van Blitterswijk, C.A., Post, J.N., Karperien, M., Metabolic programming of mesenchymal stromal cells by oxygen tension directs chondrogenic cell fate. Proc. Natl. Acad. Sci. U. S. A. 111 (2014), 13954–13959, 10.1073/pnas.1410977111.
Robins, J.C., Akeno, N., Mukherjee, A., Dalal, R.R., Aronow, B.J., Koopman, P., Clemens, T.L., Hypoxia induces chondrocyte-specific gene expression in mesenchymal cells in association with transcriptional activation of Sox9. Bone. 37 (2005), 313–322, 10.1016/j.bone.2005.04.040.
Kang, H.W., Lee, S.J., Ko, I.K., Kengla, C., Yoo, J.J., Atala, A., A 3D bioprinting system to produce human-scale tissue constructs with structural integrity. Nat. Biotechnol. 34 (2016), 312–319, 10.1038/nbt.3413.
Scotti, C., Piccinini, E., Takizawa, H., Todorov, A., Bourgine, P., Papadimitropoulos, A., Barbero, A., Manz, M.G., Martin, I., Engineering of a functional bone organ through endochondral ossification. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), 3997–4002, 10.1073/pnas.1220108110.
Suvarnapathaki, S., Wu, X., Lantigua, D., Nguyen, M.A., Camci-Unal, G., Breathing life into engineered tissues using oxygen-releasing biomaterials. NPG Asia Mater., 11, 2019, 10.1038/s41427-019-0166-2.
Canadas, R.F., Ren, T., Marques, A.P., Oliveira, J.M., Reis, R.L., Demirci, U., Biochemical gradients to generate 3D heterotypic-like tissues with isotropic and anisotropic architectures. Adv. Funct. Mater., 28, 2018, 10.1002/adfm.201804148.
Söhling, N., Neijhoft, J., Nienhaus, V., Acker, V., Harbig, J., Menz, F., Ochs, J., Verboket, R.D., Ritz, U., Blaeser, A., Dörsam, E., Frank, J., Marzi, I., Henrich, D., 3D-printing of hierarchically designed and osteoconductive bone tissue engineering scaffolds. Materials (Basel), 13, 2020, 10.3390/MA13081836.
McCormack, A., Highley, C.B., Leslie, N.R., Melchels, F.P.W., 3D printing in suspension baths: keeping the promises of bioprinting afloat. Trends Biotechnol. 38 (2020), 584–593, 10.1016/j.tibtech.2019.12.020.
Weigand, A., Horch, R.E., Boos, A.M., Beier, J.P., Arkudas, A., The arteriovenous loop: Engineering of axially vascularized tissue. Eur. Surg. Res. 59 (2018), 286–299, 10.1159/000492417.
Boos, A.M., Loew, J.S., Weigand, A., Deschler, G., Klumpp, D., Arkudas, A., Bleiziffer, O., Gulle, H., Kneser, U., Horch, R.E., Beier, J.P., Engineering axially vascularized bone in the sheep arteriovenous-loop model. J. Tissue Eng. Regen. Med. 7 (2013), 654–664, 10.1002/term.1457.
Kokemüller, H., Jehn, P., Spalthoff, S., Essig, H., Tavassol, F., Schumann, P., Andreae, A., Nolte, I., Jagodzinski, M., Gellrich, N.C., En bloc prefabrication of vascularized bioartificial bone grafts in sheep and complete workflow for custom-made transplants. Int. J. Oral Maxillofac. Surg. 43 (2014), 163–172, 10.1016/j.ijom.2013.10.013.
Tatara, A.M., Koons, G.L., Watson, E., Piepergerdes, T.C., Shah, S.R., Smith, B.T., Shum, J., Melville, J.C., Hanna, I.A., Demian, N., Ho, T., Ratcliffe, A., Van Den Beucken, J.J.J.P., Jansen, J.A., Wong, M.E., Mikos, A.G., Biomaterials-aided mandibular reconstruction using in vivo bioreactors. Proc. Natl. Acad. Sci. U. S. A 116 (2019), 6954–6963, 10.1073/pnas.1819246116.
Stegen, S., Van Gastel, N., Eelen, G., Ghesquière, B., D'Anna, F., Thienpont, B., Goveia, J., Torrekens, S., Van Looveren, R., Luyten, F.P., Maxwell, P.H., Wielockx, B., Lambrechts, D., Fendt, S.M., Carmeliet, P., Carmeliet, G., HIF-1α promotes glutamine-mediated redox homeostasis and glycogen-dependent bioenergetics to support postimplantation bone cell survival. Cell Metab. 23 (2016), 265–279, 10.1016/j.cmet.2016.01.002.
Lee, J.S., Kim, B.S., Seo, D., Park, J.H., Cho, D.W., Three-dimensional cell printing of large-volume tissues: application to ear regeneration. Tissue Eng. - Part C Methods. 23 (2017), 136–145, 10.1089/ten.tec.2016.0362.
Orth, P., Madry, H., Advancement of the subchondral bone plate in translational models of osteochondral repair: implications for tissue engineering approaches. Tissue Eng. - Part B Rev. 21 (2015), 504–520, 10.1089/ten.teb.2015.0122.
Mills, L.A., Simpson, A.H.R.W., In vivo models of bone repair. J. Bone Jt. Surg. - Ser. B. 94:B (2012), 865–874, 10.1302/0301-620X.94B7.27370.
Lammens, J., Maréchal, M., Geris, L., Van der Aa, J., Van Hauwermeiren, H., Luyten, F.P., Delport, H., Warning About the Use of Critical-Size Defects for the Translational Study of Bone Repair: Analysis of a Sheep Tibial Model. Tissue Eng. Part C Methods. 23 (2017), 694–699, 10.1089/ten.tec.2017.0147.
Dias, I.R., Viegas, C.A., Carvalho, P.P., Large animal models for osteochondral regeneration. Adv. Exp. Med. Biol., 2018, 441–501, 10.1007/978-3-319-76735-2_20.
Freeman, F.E., Brennan, M., Browe, D.C., Renaud, A., De Lima, J., Kelly, D.J., McNamara, L.M., Layrolle, P., A developmental engineering-based approach to bone repair: endochondral priming enhances vascularization and new bone formation in a critical size defect. Front. Bioeng. Biotechnol., 8, 2020, 230, 10.3389/fbioe.2020.00230.
Smith, J.O., Tayton, E.R., Khan, F., Aarvold, A., Cook, R.B., Goodship, A., Bradley, M., Oreffo, R.O.C., Large animal in vivo evaluation of a binary blend polymer scaffold for skeletal tissue-engineering strategies; translational issues. J. Tissue Eng. Regen. Med. 11 (2017), 1065–1076, 10.1002/term.2007.
Reichert, J.C., Cipitria, A., Epari, D.R., Saifzadeh, S., Krishnakanth, P., Berner, A., Woodruff, M.A., Schell, H., Mehta, M., Schuetz, M.A., Duda, G.N., Hutmacher, D.W., A tissue engineering solution for segmental defect regeneration in load-bearing long bones. Sci. Transl. Med., 4, 2012, 10.1126/scitranslmed.3003720.
Runyan, C.M., Vu, A.T., Rumburg, A., Bove, K., Racadio, J., Billmire, D.A., Taylor, J.A., Repair of a critical porcine tibial defect by means of allograft revitalization. Plast. Reconstr. Surg., 2015, 10.1097/PRS.0000000000001637 461e-473e.
Fernandes, M.B.C., Guimarães, J.A.M., Casado, P.L., Cavalcanti, S., Gonçalves, N.N., Ambrósio, C.E., Rodrigues, F., Pinto, A.C.F., Miglino, M.A., Duarte, M.E.L., The effect of bone allografts combined with bone marrow stromal cells on the healing of segmental bone defects in a sheep model. BMC Vet. Res., 10, 2014, 10.1186/1746-6148-10-36.
Berner, A., Henkel, J., Woodruff, M.A., Steck, R., Nerlich, M., Schuetz, M.A., Hutmacher, D.W., Delayed minimally invasive injection of allogenic bone marrow stromal cell sheets regenerates large bone defects in an ovine preclinical animal model. Stem Cells Transl. Med. 4 (2015), 503–512, 10.5966/sctm.2014-0244.
Field, J.R., McGee, M., Wildenauer, C., Kurmis, A., Margerrison, E., The utilization of a synthetic bone void filler (JAX) in the repair of a femoral segmental defect. Vet. Comp. Orthop. Traumatol. 22 (2009), 87–95, 10.3415/VCOT-08-02-0019.
Meigs, L., Smirnova, L., Rovida, C., Leist, M., Hartung, T., Animal testing and its alternatives - the most important omics is economics. ALTEX. 35 (2018), 275–305, 10.14573/altex.1807041.
Pievani, A., Sacchetti, B., Corsi, A., Rambaldi, B., Donsante, S., Scagliotti, V., Vergani, P., Remoli, C., Biondi, A., Robey, P.G., Riminucci, M., Serafin, M., Human umbilical cord blood-borne fibroblasts contain marrow niche precursors that form a bone/marrow organoid in vivo. Dev. 144 (2017), 1035–1044, 10.1242/dev.142836.
Freeman, F.E., Allen, A.B., Stevens, H.Y., Guldberg, R.E., McNamara, L.M., Effects of in vitro endochondral priming and pre-vascularisation of human MSC cellular aggregates in vivo. Stem Cell Res. Ther., 6, 2015, 218, 10.1186/s13287-015-0210-2.
Sheehy, E.J., Mesallati, T., Kelly, L., Vinardell, T., Buckley, C.T., Kelly, D.J., Tissue engineering whole bones through endochondral ossification: Regenerating the distal phalanx, Biores. Open Access. 4 (2015), 229–241, 10.1089/biores.2015.0014.
Sheehy, E.J., Mesallati, T., Vinardell, T., Kelly, D.J., Engineering cartilage or endochondral bone: A comparison of different naturally derived hydrogels. Acta Biomater. 13 (2015), 245–253, 10.1016/j.actbio.2014.11.031.
Jukes, J.M., Both, S.K., Leusink, A., Sterk, L.M.T., Van Blitterswijk, C.A., De Boer, J., Endochondral bone tissue engineering using embryonic stem cells. Proc. Natl. Acad. Sci. U. S. A. 105 (2008), 6840–6845, 10.1073/pnas.0711662105.
Visser, J., Gawlitta, D., Benders, K.E.M., Toma, S.M.H., Pouran, B., van Weeren, P.R., Dhert, W.J.A., Malda, J., Endochondral bone formation in gelatin methacrylamide hydrogel with embedded cartilage-derived matrix particles. Biomaterials. 37 (2015), 174–182, 10.1016/j.biomaterials.2014.10.020.
Guerrero, J., Pigeot, S., Müller, J., Schaefer, D.J., Martin, I., Scherberich, A., Fractionated human adipose tissue as a native biomaterial for the generation of a bone organ by endochondral ossification. Acta Biomater. 77 (2018), 142–154, 10.1016/j.actbio.2018.07.004.
Reinisch, A., Hernandez, D.C., Schallmoser, K., Majeti, R., Generation and use of a humanized bone-marrow-ossicle niche for hematopoietic xenotransplantation into mice. Nat. Protoc. 12 (2017), 2169–2178, 10.1038/nprot.2017.088.
Reinisch, A., Thomas, D., Corces, M.R., Zhang, X., Gratzinger, D., Hong, W.J., Schallmoser, K., Strunk, D., Majeti, R., A humanized bone marrow ossicle xenotransplantation model enables improved engraftment of healthy and leukemic human hematopoietic cells. Nat. Med. 22 (2016), 812–821, 10.1038/nm.4103.
Osinga, R., Di Maggio, N., Todorov, A., Allafi, N., Barbero, A., Laurent, F., Schaefer, D.J., Martin, I., Scherberich, A., Generation of a bone organ by human adipose-derived stromal cells through endochondral ossification. Stem Cells Transl. Med. 5 (2016), 1090–1097, 10.5966/sctm.2015-0256.
Roberts, S.J., Geris, L., Kerckhofs, G., Desmet, E., Schrooten, J., Luyten, F.P., The combined bone forming capacity of human periosteal derived cells and calcium phosphates. Biomaterials. 32 (2011), 4393–4405, 10.1016/j.biomaterials.2011.02.047.
Stüdle, C., Vallmajó-Martín, Q., Haumer, A., Guerrero, J., Centola, M., Mehrkens, A., Schaefer, D.J., Ehrbar, M., Barbero, A., Martin, I., Spatially confined induction of endochondral ossification by functionalized hydrogels for ectopic engineering of osteochondral tissues. Biomaterials. 171 (2018), 219–229, 10.1016/j.biomaterials.2018.04.025.
Sarem, M., Heizmann, M., Barbero, A., Martin, I., Prasad Shastri, V., Hyperstimulation of CaSR in human MSCs by biomimetic apatite inhibits endochondral ossification via temporal down-regulation of PTH1R. Proc. Natl. Acad. Sci. U. S. A. 115 (2018), E6135–E6144, 10.1073/pnas.1805159115.
Yang, W., Both, S.K., Van Osch, G.J.V.M., Wang, Y., Jansen, J.A., Yang, F., Effects of in vitro chondrogenic priming time of bone-marrow-derived mesenchymal stromal cells on in vivo endochondral bone formation. Acta Biomater. 13 (2015), 254–265, 10.1016/j.actbio.2014.11.029.
Alsberg, E., Anderson, K.W., Albeiruti, A., Rowley, J.A., Mooney, D.J., Engineering growing tissues. Proc. Natl. Acad. Sci. U. S. A. 99 (2002), 12025–12030, 10.1073/pnas.192291499.
Bourgine, P.E., Scotti, C., Pigeot, S., Tchang, L.A., Todorov, A., Martin, I., Osteoinductivity of engineered cartilaginous templates devitalized by inducible apoptosis. Proc. Natl. Acad. Sci. U. S. A. 111 (2014), 17426–17431, 10.1073/pnas.1411975111.
Mumme, M., Scotti, C., Papadimitropoulos, A., Todorov, A., Hoffmann, W., Bocelli-Tyndall, C., Jakob, M., Wendt, D., Martin, I., Barbero, A., Interleukin-1β modulates endochondral ossification by human adult bone marrow stromal cells, Eur. Cells. Mater. 24 (2012), 224–236, 10.22203/eCM.v024a16.
Huang, R.L., Guerrero, J., Senn, A.S., Kappos, E.A., Liu, K., Li, Q., Dufrane, D., Schaefer, D.J., Martin, I., Scherberich, A., Dispersion of ceramic granules within human fractionated adipose tissue to enhance endochondral bone formation. Acta Biomater. 102 (2020), 458–467, 10.1016/j.actbio.2019.11.046.
Fritsch, K., Pigeot, S., Feng, X., Bourgine, P.E., Schroeder, T., Martin, I., Manz, M.G., Takizawa, H., Engineered humanized bone organs maintain human hematopoiesis in vivo. Exp. Hematol., 61, 2018, 10.1016/j.exphem.2018.01.004 45-51.e5.
Bahney, C.S., Hu, D.P., Taylor, A.J., Ferro, F., Britz, H.M., Hallgrimsson, B., Johnstone, B., Miclau, T., Marcucio, R.S., Stem cell-derived endochondral cartilage stimulates bone healing by tissue transformation. J. Bone Miner. Res. 29 (2014), 1269–1282, 10.1002/jbmr.2148.
Van Gastel, N., Stegen, S., Stockmans, I., Moermans, K., Schrooten, J., Graf, D., Luyten, F.P., Carmeliet, G., Expansion of murine periosteal progenitor cells with fibroblast growth factor 2 reveals an intrinsic endochondral ossification program mediated by bone morphogenetic protein 2. Stem Cells 32 (2014), 2407–2418, 10.1002/stem.1783.
Huang, J.I., Durbhakula, M.M., Angele, P., Johnstone, B., Yoo, J.U., Lunate arthroplasty with autologous mesenchymal stem cells in a rabbit model. J. Bone Jt. Surg. - Ser. A. 88 (2006), 744–752, 10.2106/JBJS.E.00669.
Cunniffe, G.M., Vinardell, T., Thompson, E.M., Daly, A.C., Matsiko, A., O'Brien, F.J., Kelly, D.J., Chondrogenically primed mesenchymal stem cell-seeded alginate hydrogels promote early bone formation in critically-sized defects. Eur. Polym. J. 72 (2015), 464–472, 10.1016/j.eurpolymj.2015.07.021.
Allen, A.B., Zimmermann, J.A., Burnsed, O.A., Yakubovich, D.C., Stevens, H.Y., Gazit, Z., McDevitt, T.C., Guldberg, R.E., Environmental manipulation to promote stem cell survival: In vivo: Use of aggregation, oxygen carrier, and BMP-2 co-delivery strategies. J. Mater. Chem. B. 4 (2016), 3594–3607, 10.1039/c5tb02471d.
van der Stok, J., Koolen, M.K.E., Jahr, H., Kops, N., Waarsing, J.H., Weinans, H., van der Jagt, O.P., Chondrogenically differentiated mesenchymal stromal cell pellets stimulate endochondral bone regeneration in critical-sized bone defects, Eur. Cells Mater. 27 (2014), 137–148, 10.22203/eCM.v027a11.
Matsiko, A., Thompson, E.M., Lloyd-Griffith, C., Cunniffe, G.M., Vinardell, T., Gleeson, J.P., Kelly, D.J., O'Brien, F.J., An endochondral ossification approach to early stage bone repair: Use of tissue-engineered hypertrophic cartilage constructs as primordial templates for weight-bearing bone repair. J. Tissue Eng. Regen. Med. 12 (2018), e2147–e2150, 10.1002/term.2638.
Harada, N., Watanabe, Y., Sato, K., Abe, S., Yamanaka, K., Sakai, Y., Kaneko, T., Matsushita, T., Bone regeneration in a massive rat femur defect through endochondral ossification achieved with chondrogenically differentiated MSCs in a degradable scaffold. Biomaterials. 35 (2014), 7800–7810, 10.1016/j.biomaterials.2014.05.052.
Bai, Y., Liu, C., Fu, L., Gong, X., Dou, C., Cao, Z., Quan, H., Li, J., Kang, F., Dai, J., Zhao, C., Dong, S., Mangiferin enhances endochondral ossification-based bone repair in massive bone defect by inducing autophagy through activating AMP-activated protein kinase signaling pathway. FASEB J. 32 (2018), 4573–4584, 10.1096/fj.201701411R.
Thompson, E.M., Matsiko, A., Kelly, D.J., Gleeson, J.P., O'Brien, F.J., An endochondral ossification-based approach to bone repair: chondrogenically primed mesenchymal stem cell-laden scaffolds support greater repair of critical-sized cranial defects than osteogenically stimulated constructs in vivo. Tissue Eng. Part A 22 (2016), 556–567, 10.1089/ten.TEA.2015.0457.
Cunniffe, G.M., Díaz-Payno, P.J., Ramey, J.S., Mahon, O.R., Dunne, A., Thompson, E.M., O'Brien, F.J., Kelly, D.J., Growth plate extracellular matrix-derived scaffolds for large bone defect healing, Eur. Cells Mater. 33 (2017), 130–142, 10.22203/eCM.v033a10.
Dang, P.N., Herberg, S., Varghai, D., Riazi, H., Varghai, D., McMillan, A., Awadallah, A., Phillips, L.M., Jeon, O., Nguyen, M.K., Dwivedi, N., Yu, X., Murphy, W.L., Alsberg, E., Endochondral ossification in critical-sized bone defects via readily implantable scaffold-free stem cell constructs. Stem Cells Transl. Med. 6 (2017), 1644–1659, 10.1002/sctm.16-0222.
Mikael, P.E., Golebiowska, A.A., Xin, X., Rowe, D.W., Nukavarapu, S.P., Evaluation of an engineered hybrid matrix for bone regeneration via endochondral ossification. Ann. Biomed. Eng. 48 (2020), 992–1005, 10.1007/s10439-019-02279-0.
Wang, C., Wang, Z., Li, A., Bai, F., Lu, J., Xu, S., Li, D., Repair of segmental bone-defect of goat's tibia using a dynamic perfusion culture tissue engineering bone. J. Biomed. Mater. Res. - Part A, 2010, 10.1002/jbm.a.32347.
Cipitria, A., Lange, C., Schell, H., Wagermaier, W., Reichert, J.C., Hutmacher, D.W., Fratzl, P., Duda, G.N., Porous scaffold architecture guides tissue formation. J. Bone Miner. Res., 2012, 10.1002/jbmr.1589.
Berner, A., Reichert, J.C., Woodruff, M.A., Saifzadeh, S., Morris, A.J., Epari, D.R., Nerlich, M., Schuetz, M.A., Hutmacher, D.W., Autologous vs. allogenic mesenchymal progenitor cells for the reconstruction of critical sized segmental tibial bone defects in aged sheep. Acta Biomater., 2013, 10.1016/j.actbio.2013.04.035.
Gardel, L.S., Afonso, M., Frias, C., Gomes, M.E., Reis, R.L., Assessing the repair of critical size bone defects performed in a goat tibia model using tissue-engineered constructs cultured in a bidirectional flow perfusion bioreactor. J. Biomater. Appl. 29 (2014), 172–185, 10.1177/0885328213519351.
Rentsch, C., Schneiders, W., Hess, R., Rentsch, B., Bernhardt, R., Spekl, K., Schneider, K., Scharnweber, D., Biewener, A., Rammelt, S., Healing properties of surface-coated polycaprolactone-co-lactide scaffolds: A pilot study in sheep. J. Biomater. Appl., 2014, 10.1177/0885328212471409.
Li, J.J., Roohani-Esfahani, S.I., Dunstan, C.R., Quach, T., Steck, R., Saifzadeh, S., Pivonka, P., Zreiqat, H., Efficacy of novel synthetic bone substitutes in the reconstruction of large segmental bone defects in sheep tibiae. Biomed. Mater., 2016, 10.1088/1748-6041/11/1/015016.
Kirby, G.T.S., White, L.J., Steck, R., Berner, A., Bogoevski, K., Qutachi, O., Jones, B., Saifzadeh, S., Hutmacher, D.W., Shakesheff, K.M., Woodruff, M.A., Microparticles for sustained growth factor delivery in the regeneration of critically-sized segmental tibial bone defects. Materials (Basel)., 2016, 10.3390/ma9040259.
Lammens, J., Maréchal, M., Delport, H., Geris, L., Oppermann, H., Vukicevic, S., Luyten, F.P., A cell-based combination product for the repair of large bone defects. Bone., 138, 2020 Sep, 115511, 10.1016/j.bone.2020.115511.
