An Osteoconductive, Osteoinductive, and Osteogenic Tissue-Engineered Product for Trauma and Orthopaedic Surgery: How Far Are We?

The management of large bone defects due to trauma, degenerative disease, congenital deformities, and tumor resection remains a complex issue for the orthopaedic reconstructive surgeons. The requirement is for an ideal bone replacement which is osteoconductive, osteoinductive, and osteogenic. Autologous bone grafts are still considered the gold standard for reconstruction of bone defects, but donor site morbidity and size limitations are major concern. The use of bioartificial bone tissues may help to overcome these problems. The reconstruction of large volume defects remains a challenge despite the success of reconstruction of small-to-moderate-sized bone defects using engineered bone tissues. The aim of this paper is to understand the principles of tissue engineering of bone and its clinical applications in reconstructive surgery.

[1]  W. Khan,et al.  Sources of Adult Mesenchymal Stem Cells Applicable for Musculoskeletal Applications - A Systematic Review of the Literature , 2011, The open orthopaedics journal.

[2]  Antonios G. Mikos,et al.  Flow Perfusion Enhances the Calcified Matrix Deposition of Marrow Stromal Cells in Biodegradable Nonwoven Fiber Mesh Scaffolds , 2005, Annals of Biomedical Engineering.

[3]  David L Kaplan,et al.  Matrix-mediated retention of osteogenic differentiation potential by human adult bone marrow stromal cells during ex vivo expansion. , 2004, Biomaterials.

[4]  A. Giobbie-Hurder,et al.  Long-term outcomes after total alloplastic temporomandibular joint reconstruction following exposure to failed materials. , 2004, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[5]  M. Sefton,et al.  Tissue engineering. , 1998, Journal of cutaneous medicine and surgery.

[6]  A. Pou.  Update on new biomaterials and their use in reconstructive surgery , 2003, Current opinion in otolaryngology & head and neck surgery.

[7]  A. Ladd,et al.  Repair of five distal radius fractures with an investigational cancellous bone cement: a preliminary report. , 1997, Journal of orthopaedic trauma.

[8]  Antonios G Mikos,et al.  Formation of three-dimensional cell/polymer constructs for bone tissue engineering in a spinner flask and a rotating wall vessel bioreactor. , 2002, Journal of biomedical materials research.

[9]  K. Leong,et al.  The design of scaffolds for use in tissue engineering. Part I. Traditional factors. , 2001, Tissue engineering.

[10]  R Langer,et al.  Novel approach to fabricate porous sponges of poly(D,L-lactic-co-glycolic acid) without the use of organic solvents. , 1996, Biomaterials.

[11]  Maurilio Marcacci,et al.  Stem cells associated with macroporous bioceramics for long bone repair: 6- to 7-year outcome of a pilot clinical study. , 2007, Tissue engineering.

[12]  P. Holtom,et al.  Comparison of Anterior and Posterior Iliac Crest Bone Grafts in Terms of Harvest-Site Morbidity and Functional Outcomes , 2002, The Journal of bone and joint surgery. American volume.

[13]  W. Khan,et al.  Advances in the use of stem cells and tissue engineering applications in bone repair. , 2012, Current stem cell research & therapy.

[14]  David R. Olsen,et al.  Recombinant collagen and gelatin for drug delivery. , 2003, Advanced drug delivery reviews.

[15]  A. Reddi,et al.  Morphogenesis and tissue engineering of bone and cartilage: inductive signals, stem cells, and biomimetic biomaterials. , 2000, Tissue engineering.

[16]  G. Wen,et al.  Preparation and biological properties of PLLA/β-TCP composites reinforced by chitosan fibers , 2008, Biomedical materials.

[17]  W. Dhert,et al.  Bone tissue engineering and spinal fusion: the potential of hybrid constructs by combining osteoprogenitor cells and scaffolds. , 2004, Biomaterials.

[18]  J. Thomson,et al.  Embryonic stem cell lines derived from human blastocysts. , 1998, Science.

[19]  S. Santavirta,et al.  Recombinant Human Bone Morphogenetic Protein-2 for Treatment of Open Tibial Fractures: A Prospective, Controlled, Randomized Study of Four Hundred and Fifty Patients , 2002, The Journal of bone and joint surgery. American volume.

[20]  Clemens A van Blitterswijk,et al.  A perfusion bioreactor system capable of producing clinically relevant volumes of tissue-engineered bone: in vivo bone formation showing proof of concept. , 2005, Biomaterials.

[21]  W. Khan,et al.  Advances and Developments in the Use of Human Mesenchymal Stem Cells – A Few Considerations , 2011, The open orthopaedics journal.

[22]  Wasim S. Khan,et al.  The role of stem cells, scaffolds and bioreactors in musculoskeletal tissue engineering , 2012 .

[23]  M. P,et al.  Adult Mesenchymal Stem Cells and Cell Surface Characterization - A Systematic Review of the Literature , 2011, The open orthopaedics journal.

[24]  N. Ueno,et al.  Bone Morphogenetic Protein 2 Stimulates Osteoclast Differentiation and Survival Supported by Receptor Activator of Nuclear Factor-κB Ligand. , 2001, Endocrinology.

[25]  W. Khan,et al.  The Use of Growth Factors and Mesenchymal Stem Cells in Orthopaedics , 2011, The open orthopaedics journal.

[26]  J. Chłopek,et al.  The influence of carbon fibres on the resorption time and mechanical properties of the lactide–glycolide co-polymer , 2007, Journal of biomaterials science. Polymer edition.

[27]  J. Gimble,et al.  Adipose-derived stem cells for regenerative medicine. , 2007, Circulation research.

[28]  S. Santavirta,et al.  The microenvironment around total hip replacement prostheses. , 2005, Clinical orthopaedics and related research.

[29]  Diane Gershon,et al.  Complex political, ethical and legal issues surround research on human embryonic stem cells. , 2003, Nature.

[30]  W. Khan,et al.  Sources of adult mesenchymal stem cells and their applicability for musculoskeletal applications. , 2012, Current stem cell research & therapy.

[31]  Kazutoshi Nozaki,et al.  A new bone‐inducing biodegradable porous β‐tricalcium phosphate , 2004 .

[32]  Hom-lay Wang,et al.  Common Implant-Related Advanced Bone Grafting Complications: Classification, Etiology, and Management , 2008, Implant dentistry.

[33]  A. Boccaccini,et al.  Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. , 2006, Biomaterials.

[34]  U Kneser,et al.  Tissue engineering of bone: the reconstructive surgeon's point of view , 2006, Journal of cellular and molecular medicine.

[35]  Wasim S. Khan,et al.  Tissue engineering approaches for bone repair: Cells, scaffolds, growth factors and gene therapy , 2012 .

[36]  J. Vacanti,et al.  Tissue engineering : Frontiers in biotechnology , 1993 .

[37]  A. Caplan.  Adult mesenchymal stem cells for tissue engineering versus regenerative medicine , 2007, Journal of cellular physiology.

[38]  M. Kumegawa,et al.  Direct stimulation of osteoclastic bone resorption by bone morphogenetic protein (BMP)-2 and expression of BMP receptors in mature osteoclasts. , 2000, Bone.

[39]  K. Yoshimura,et al.  Heterotopic Ossification of Degenerating Rat Skeletal Muscle Induced by Adenovirus‐Mediated Transfer of Bone Morphogenetic Protein‐2 Gene , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[40]  W. Khan,et al.  The Role of Bioreactors in Tissue Engineering for Musculoskeletal Applications , 2011, The open orthopaedics journal.

[41]  G. Murray,et al.  The efficacy of the Pavlik harness, the Craig splint and the von Rosen splint in the management of neonatal dysplasia of the hip. A comparative study. , 2002, The Journal of bone and joint surgery. British volume.

[42]  D E Ingber,et al.  Preparation of poly(glycolic acid) bonded fiber structures for cell attachment and transplantation. , 1993, Journal of biomedical materials research.

[43]  H. Terai,et al.  A new bone-inducing biodegradable porous beta-tricalcium phosphate. , 2004, Journal of biomedical materials research. Part A.

[44]  P. Aspenberg,et al.  Injectable Calcium Phosphate in the Treatment of Distal Radial Fractures , 1996, Journal of hand surgery.

[45]  Swee Hin Teoh,et al.  Repair of calvarial defects with customised tissue-engineered bone grafts II. Evaluation of cellular efficiency and efficacy in vivo. , 2003, Tissue engineering.

[46]  Antonios G Mikos,et al.  Modulation of cell differentiation in bone tissue engineering constructs cultured in a bioreactor. , 2006, Advances in experimental medicine and biology.

[47]  Wasim S Khan,et al.  Stem Cell Applications and Tissue Engineering Approaches in Surgical Practice , 2009, Journal of perioperative practice.

[48]  E. Schwarz,et al.  Review: gene- and stem cell-based therapeutics for bone regeneration and repair. , 2007, Tissue engineering.

[49]  M. Shaw,et al.  Biodegradable HA-PLA 3-D porous scaffolds: effect of nano-sized filler content on scaffold properties. , 2005, Acta biomaterialia.

[50]  Mara Riminucci,et al.  Bone Marrow Stromal Stem Cells: Nature, Biology, and Potential Applications , 2001, Stem cells.

[51]  S. Yamanaka,et al.  Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors , 2006, Cell.

[52]  Shinya Yamanaka,et al.  Generation of Mouse Induced Pluripotent Stem Cells Without Viral Vectors , 2008, Science.

[53]  R Langer,et al.  Laminated three-dimensional biodegradable foams for use in tissue engineering. , 1993, Biomaterials.

[54]  K. Popat,et al.  Bone tissue engineering: A review in bone biomimetics and drug delivery strategies , 2009, Biotechnology progress.

[55]  Takehisa Matsuda,et al.  Human endothelial progenitor cell-seeded hybrid graft: proliferative and antithrombogenic potentials in vitro and fabrication processing. , 2003, Tissue engineering.

[56]  J. Borke,et al.  An isolation and in vitro culturing method for human intraoral bone cells derived from dental implant preparation sites. , 1998, Clinical Oral Implants Research.

[57]  Paul H Wooley,et al.  Effect of porosity and pore size on microstructures and mechanical properties of poly-epsilon-caprolactone- hydroxyapatite composites. , 2008, Journal of biomedical materials research. Part B, Applied biomaterials.

[58]  R. Guldberg,et al.  Periosteal Progenitor Cell Fate in Segmental Cortical Bone Graft Transplantations: Implications for Functional Tissue Engineering , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[59]  A. Meunier,et al.  Tissue-engineered bone regeneration , 2000, Nature Biotechnology.

[60]  W. Khan,et al.  The Role of Bone Marrow-Derived Mesenchymal Stem Cells in Sports Injuries , 2010 .

[61]  Giorgio Iannetti,et al.  Bone autografting of the calvaria and craniofacial skeleton: historical background, surgical results in a series of 15 patients, and review of the literature. , 2003, Surgical neurology.

[62]  G. Muschler,et al.  Bone cells and matrices in orthopedic tissue engineering. , 2000, The Orthopedic clinics of North America.

[63]  W. Khan,et al.  Clinical applications of mesenchymal stem cells in the treatment of fracture non-union and bone defects. , 2012, Current stem cell research & therapy.

[64]  H. Lorenz,et al.  Multilineage cells from human adipose tissue: implications for cell-based therapies. , 2001, Tissue engineering.

[65]  G. Evans,et al.  In vivo osteogenic potential of human adipose-derived stem cells/poly lactide-co-glycolic acid constructs for bone regeneration in a rat critical-sized calvarial defect model. , 2007, Tissue engineering.

[66]  R. Oreffo,et al.  Gene delivery in bone tissue engineering: progress and prospects using viral and nonviral strategies. , 2004, Tissue engineering.

[67]  Antonios G Mikos,et al.  Design of a flow perfusion bioreactor system for bone tissue-engineering applications. , 2003, Tissue engineering.

[68]  Eleftherios Tsiridis,et al.  Bone substitutes: an update. , 2005, Injury.

[69]  A. Ruys,et al.  Biodegradable poly(alpha-hydroxy acid) polymer scaffolds for bone tissue engineering. , 2010, Journal of biomedical materials research. Part B, Applied biomaterials.

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

[71]  P. Giannoudis,et al.  Application of recombinant BMP-7 on persistent upper and lower limb non-unions. , 2005, Injury.

[72]  R. Schmelzeisen,et al.  Tissue-engineered bone for maxillary sinus augmentation. , 2004, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[73]  K. Takaoka,et al.  Repair of segmental defects in rabbit humeri with titanium fiber mesh cylinders containing recombinant human bone morphogenetic protein-2 (rhBMP-2) and a synthetic polymer. , 2002, Journal of biomedical materials research.

[74]  Adam J Starr,et al.  Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures. , 2003, The Journal of bone and joint surgery. American volume.

[75]  Rodolfo Quarto,et al.  Cell Therapy for Bone Disease: A Review of Current Status , 2003, Stem cells.

[76]  D. Marsh,et al.  The Effect of Changes in Oxygen Tension during Fracture Repair on Mesenchymal Stem Cell and Bone Activities , 2009 .

[77]  Cato T Laurencin,et al.  Nanobiomaterial applications in orthopedics , 2007, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[78]  Yi Tang,et al.  TGF-β1-induced Migration of Bone Mesenchymal Stem Cells Couples Bone Resorption and Formation , 2009, Nature Medicine.

[79]  K. An,et al.  Mechanical properties of a biodegradable bone regeneration scaffold. , 2000, Journal of biomechanical engineering.

[80]  W. Khan,et al.  Tissue Engineering for Bone Production- Stem Cells, Gene Therapy and Scaffolds , 2011, The open orthopaedics journal.

[81]  J. Luider,et al.  Factors predicting engraftment of autologous blood stem cells: CD34+ subsets inferior to the total CD34+ cell dose , 1999, Bone Marrow Transplantation.

[82]  Jessica D. Kaufman,et al.  Nanomechanical analysis of bone tissue engineering scaffolds. , 2007, Journal of biomedical materials research. Part A.

[83]  T. Hardingham,et al.  The epitope characterisation and the osteogenic differentiation potential of human fat pad-derived stem cells is maintained with ageing in later life. , 2009, Injury.

[84]  Dietmar W Hutmacher,et al.  Periosteal cells in bone tissue engineering. , 2003, Tissue engineering.

[85]  W. Khan,et al.  Tissue Engineering in Orthopaedics and Musculoskeletal Sciences , 2011, The open orthopaedics journal.

[86]  M. Pera,et al.  Characterization and culture of human embryonic stem cells. , 2003, Trends in cardiovascular medicine.