Engineering bone: challenges and obstacles

Repair of large bone defects is still a challenge for the orthopaedic, reconstructive and maxillo‐facial surgeon. Availability of pluripotent stem cells from either autologous or allogenic sources and the potential of inducing the osteogenic phenotype is motivating exploration and development of custom‐tailored materials known as “bioengineered bone constructs”. In such cases, the clinical scenario involves either expansion of stem cells in monolayer and loading them into a porous scaffold prior to surgery or direct cell expansion within the scaffold, and implanting this novel construct back into the donor patient. In this review, we delineate, from an engineering perspective, the progress that has been made to date and the challenges remaining in successfully translating this promising (but not yet definitively established) approach from bench to the bedsite.

[1]  V. Bousson,et al.  De novo reconstruction of functional bone by tissue engineering in the metatarsal sheep model. , 2005, Tissue engineering.

[2]  Frédéric Chaubet,et al.  Retention of transforming growth factor beta1 using functionalized dextran-based hydrogels. , 2005, Biomaterials.

[3]  R. Löbenberg,et al.  Imparting bone mineral affinity to osteogenic proteins through heparin-bisphosphonate conjugates. , 2004, Journal of Controlled Release.

[4]  Rui L Reis,et al.  Bone tissue engineering: state of the art and future trends. , 2004, Macromolecular bioscience.

[5]  Andrés J. García,et al.  α2β1 integrin‐specific collagen‐mimetic surfaces supporting osteoblastic differentiation , 2004 .

[6]  A. Flake,et al.  Mesenchymal stem cells: paradoxes of passaging. , 2004, Experimental hematology.

[7]  Christopher H Contag,et al.  Adipose-derived adult stromal cells heal critical-size mouse calvarial defects , 2004, Nature Biotechnology.

[8]  F. Barry,et al.  Mesenchymal stem cells: clinical applications and biological characterization. , 2004, The international journal of biochemistry & cell biology.

[9]  J. Fisher,et al.  Effect of biomaterial properties on bone healing in a rabbit tooth extraction socket model. , 2004, Journal of biomedical materials research. Part A.

[10]  W. Otto,et al.  Tomorrow's skeleton staff: mesenchymal stem cells and the repair of bone and cartilage , 2004, Cell proliferation.

[11]  D. Wendt,et al.  The role of bioreactors in tissue engineering. , 2004, Trends in biotechnology.

[12]  F. Djouad,et al.  Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. , 2003, Blood.

[13]  Antonios G Mikos,et al.  Biomimetic materials for tissue engineering. , 2003, Biomaterials.

[14]  J. Davies,et al.  Use of a biomimetic strategy to engineer bone. , 2003, Journal of biomedical materials research. Part A.

[15]  K. Leong,et al.  Solid freeform fabrication of three-dimensional scaffolds for engineering replacement tissues and organs. , 2003, Biomaterials.

[16]  A J Verbout,et al.  Viable osteogenic cells are obligatory for tissue-engineered ectopic bone formation in goats. , 2003, Tissue engineering.

[17]  E. Guinan,et al.  Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation , 2003, Transplantation.

[18]  O. Ringdén,et al.  Mesenchymal Stem Cells Inhibit and Stimulate Mixed Lymphocyte Cultures and Mitogenic Responses Independently of the Major Histocompatibility Complex , 2003, Scandinavian journal of immunology.

[19]  H. Petite,et al.  Marrow Stromal Stem Cells for Repairing the Skeleton , 2002, Biotechnology & genetic engineering reviews.

[20]  H. Jennissen,et al.  Accelerated and Improved Osteointegration of Implants Biocoated with Bone Morphogenetic Protein 2 (BMP‐2) , 2002, Annals of the New York Academy of Sciences.

[21]  C. Carlo-Stella,et al.  Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. , 2002, Blood.

[22]  J. Wozney,et al.  Delivering on the promise of bone morphogenetic proteins. , 2001, Trends in biotechnology.

[23]  J. Wozney,et al.  Delivery Systems for BMPs: Factors Contributing to Protein Retention at an Application Site , 2001, The Journal of bone and joint surgery. American volume.

[24]  David J. Mooney,et al.  Promoting Angiogenesis in Engineered Tissues , 2001, Journal of drug targeting.

[25]  J Bonadio,et al.  Tissue engineering via local gene delivery: update and future prospects for enhancing the technology. , 2000, Advanced drug delivery reviews.

[26]  C. Kirker-Head,et al.  Potential applications and delivery strategies for bone morphogenetic proteins. , 2000, Advanced drug delivery reviews.

[27]  T. Kohgo,et al.  Effects of geometry of hydroxyapatite as a cell substratum in BMP-induced ectopic bone formation. , 2000, Journal of Biomedical Materials Research.

[28]  J. Hubbell,et al.  Development of fibrin derivatives for controlled release of heparin-binding growth factors. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[29]  A Boyde,et al.  Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones. , 2000, Journal of biomedical materials research.

[30]  E. Shors Coralline bone graft substitutes. , 1999, The Orthopedic clinics of North America.

[31]  P. Schiller,et al.  Age‐Related Osteogenic Potential of Mesenchymal Stromal Stem Cells from Human Vertebral Bone Marrow , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[32]  K E Healy,et al.  Designing Biomaterials to Direct Biological Responses , 1999, Annals of the New York Academy of Sciences.

[33]  V. Goldberg,et al.  The Effect of Implants Loaded with Autologous Mesenchymal Stem Cells on the Healing of Canine Segmental Bone Defects* , 1998, The Journal of bone and joint surgery. American volume.

[34]  R. Bizios,et al.  Design and function of novel osteoblast-adhesive peptides for chemical modification of biomaterials. , 1998, Journal of biomedical materials research.

[35]  W. Hayes,et al.  Bone regeneration by implantation of purified, culture‐expanded human mesenchymal stem cells , 1998, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[36]  H. Ohgushi,et al.  BMP-induced osteogenesis on the surface of hydroxyapatite with geometrically feasible and nonfeasible structures: topology of osteogenesis. , 1998, Journal of biomedical materials research.

[37]  M J Yaszemski,et al.  Ectopic bone formation by marrow stromal osteoblast transplantation using poly(DL-lactic-co-glycolic acid) foams implanted into the rat mesentery. , 1997, Journal of biomedical materials research.

[38]  R. Midura,et al.  Characterization of human bone marrow stromal cells with respect to osteoblastic differentiation , 1997, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[39]  S. Kadiyala,et al.  Culture-expanded, bone marrow-derived mesenchymal stem cells can regenerate a critical-sized segmental bone defect , 1997 .

[40]  D. Rowe,et al.  Bone formation in vivo: comparison of osteogenesis by transplanted mouse and human marrow stromal fibroblasts. , 1997, Transplantation.

[41]  S. Bruder,et al.  Osteogenic differentiation of purified, culture‐expanded human mesenchymal stem cells in vitro , 1997, Journal of cellular biochemistry.

[42]  S. Bruder,et al.  Growth kinetics, self‐renewal, and the osteogenic potential of purified human mesenchymal stem cells during extensive subcultivation and following cryopreservation , 1997, Journal of cellular biochemistry.

[43]  C. Colton,et al.  Implantable biohybrid artificial organs. , 1995, Cell transplantation.

[44]  Jeffrey A. Hubbell,et al.  Biomaterials in Tissue Engineering , 1995, Bio/Technology.

[45]  T A Einhorn,et al.  Enhancement of fracture-healing. , 1995, The Journal of bone and joint surgery. American volume.

[46]  Robert Langer,et al.  Preparation and characterization of poly(l-lactic acid) foams , 1994 .

[47]  A. Reddi,et al.  The critical role of geometry of porous hydroxyapatite delivery system in induction of bone by osteogenin, a bone morphogenetic protein. , 1992, Matrix.

[48]  S. Furner,et al.  Musculoskeletal Conditions in the United States , 1992 .

[49]  C J Damien,et al.  Bone graft and bone graft substitutes: a review of current technology and applications. , 1991, Journal of applied biomaterials : an official journal of the Society for Biomaterials.

[50]  V. Goldberg,et al.  Osteogenic potential of culture-expanded rat marrow cells as assayed in vivo with porous calcium phosphate ceramic. , 1991, Biomaterials.

[51]  P. Iványi,et al.  H-2-dependent binding of xenogeneic beta 2-microglobulin from culture media. , 1988, Journal of immunology.

[52]  C. Joyner,et al.  Clonal analysis in vitro of osteogenic differentiation of marrow CFU-F. , 1987, Journal of cell science.

[53]  H. Gabbert,et al.  Oxygenation and differentiation in multicellular spheroids of human colon carcinoma. , 1986, Cancer research.

[54]  A. Reddi,et al.  Importance of geometry of the extracellular matrix in endochondral bone differentiation , 1984, The Journal of cell biology.

[55]  MacDermott Rp,et al.  Fetal calf serum augmentation during cell separation procedures accounts for the majority of human autologous mixed leukocyte reactivity. , 1983 .

[56]  J. Folkman,et al.  SELF-REGULATION OF GROWTH IN THREE DIMENSIONS , 1973, The Journal of experimental medicine.

[57]  A. Friedenstein,et al.  Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. , 1968, Transplantation.

[58]  Andrés J. García,et al.  Alpha2beta1 integrin-specific collagen-mimetic surfaces supporting osteoblastic differentiation. , 2004, Journal of biomedical materials research. Part A.

[59]  Kevin McIntosh,et al.  Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. , 2002, Experimental hematology.

[60]  A I Caplan,et al.  Stem cell technology and bioceramics: from cell to gene engineering. , 1999, Journal of biomedical materials research.

[61]  K E Healy,et al.  Biomimetic Peptide Surfaces That Regulate Adhesion, Spreading, Cytoskeletal Organization, and Mineralization of the Matrix Deposited by Osteoblast‐like Cells , 1999, Biotechnology progress.

[62]  J. A. Cooper,et al.  Tissue engineering: orthopedic applications. , 1999, Annual review of biomedical engineering.

[63]  N. Endo,et al.  Number of osteoprogenitor cells in human bone marrow markedly decreases after skeletal maturation , 1999, Journal of Bone and Mineral Metabolism.

[64]  J. Wozney The bone morphogenetic protein family: multifunctional cellular regulators in the embryo and adult. , 1998, European journal of oral sciences.

[65]  B D Boyan,et al.  Role of material surfaces in regulating bone and cartilage cell response. , 1996, Biomaterials.

[66]  A I Caplan,et al.  Characterization of cells with osteogenic potential from human marrow. , 1992, Bone.

[67]  R. Macdermott,et al.  Fetal calf serum augmentation during cell separation procedures accounts for the majority of human autologous mixed leukocyte reactivity. , 1983, Behring Institute Mitteilungen.