The ABJS Nicolas Andry Award: Tissue engineering of bone and ligament: a 15-year perspective.

Musculoskeletal repair is a major challenge for orthopaedic surgeons. The burden of repair is compounded by supply constraints and morbidity associated with autograft and allograft tissue. We report 15 years of research regarding tissue engineering and biological substitutes for bone and ligaments. Our approach has focused on biomaterial selection, scaffold development, cell selection, cell/material interaction, and growth factor delivery. We have extensively tested poly(ester), poly(anhydride), poly(phosphazene) derivatives, and composite materials using biocompatibility, degradation, and mechanical analyses for bone and ligament tissue engineering. We have developed novel three-dimensional matrices with a pore structure and mechanical properties similar to native tissue. We also have reported on the attachment, growth, proliferation, and differentiation of cells cultured on several scaffolds. Through extensive molecular analysis, in vitro culture condition analysis, and in vivo evaluation, our findings provide new methods of bone tissue regeneration using three-dimensional tissue engineered scaffolds, bioactive bone cement composite materials, and three-dimensional tissue engineered scaffolds for ligament regeneration.

[1]  J. A. Cooper,et al.  Evaluation of the anterior cruciate ligament, medial collateral ligament, achilles tendon and patellar tendon as cell sources for tissue-engineered ligament. , 2006, Biomaterials.

[2]  C T Laurencin,et al.  Preliminary in vivo report on the osteocompatibility of poly(anhydride-co-imides) evaluated in a tibial model. , 1998, Journal of biomedical materials research.

[3]  J. B. Liesch,et al.  Development of fibroblast-seeded ligament analogs for ACL reconstruction. , 1995, Journal of biomedical materials research.

[4]  J H Brekke,et al.  Principles of tissue engineering applied to programmable osteogenesis. , 1998, Journal of biomedical materials research.

[5]  Michel Vert,et al.  Aliphatic polyesters: great degradable polymers that cannot do everything. , 2005, Biomacromolecules.

[6]  C T Laurencin,et al.  Proliferation, morphology, and protein expression by osteoblasts cultured on poly(anhydride-co-imides). , 1999, Journal of biomedical materials research.

[7]  Cato T Laurencin,et al.  The sintered microsphere matrix for bone tissue engineering: in vitro osteoconductivity studies. , 2002, Journal of biomedical materials research.

[8]  X Zhang,et al.  Bone induction by porous glass ceramic made from Bioglass (45S5). , 2001, Journal of biomedical materials research.

[9]  C. Cornell,et al.  Osteoconductive materials and their role as substitutes for autogenous bone grafts. , 1999, The Orthopedic clinics of North America.

[10]  G. Daculsi,et al.  Formation of carbonate-apatite crystals after implantation of calcium phosphate ceramics , 2007, Calcified Tissue International.

[11]  J C Middleton,et al.  Synthetic biodegradable polymers as orthopedic devices. , 2000, Biomaterials.

[12]  C T Laurencin,et al.  Immunofluorescence and confocal laser scanning microscopy studies of osteoblast growth and phenotypic expression in three-dimensional degradable synthetic matrices. , 1995, Journal of biomedical materials research.

[13]  Cato T Laurencin,et al.  Genetically modified mesodermal-derived cells for bone tissue engineering. , 2003, IEEE engineering in medicine and biology magazine : the quarterly magazine of the Engineering in Medicine & Biology Society.

[14]  G. Gheysen,et al.  Bioglass composites: a potential material for dental application. , 1983, Biomaterials.

[15]  Cato T Laurencin,et al.  Integrin expression by human osteoblasts cultured on degradable polymeric materials applicable for tissue engineered bone , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[16]  Cato T Laurencin,et al.  Novel polymer-synthesized ceramic composite-based system for bone repair: an in vitro evaluation. , 2004, Journal of biomedical materials research. Part A.

[17]  D. Bradford,et al.  Calcium sulfate- and calcium phosphate-based bone substitutes. Mimicry of the mineral phase of bone. , 1999, The Orthopedic clinics of North America.

[18]  Frederick H. Silver,et al.  Biomaterials, Medical Devices and Tissue Engineering: An Integrated Approach , 1993 .

[19]  Cato T Laurencin,et al.  Quantitative analysis of three-dimensional fluid flow in rotating bioreactors for tissue engineering. , 2004, Journal of biomedical materials research. Part A.

[20]  R. Guidoin,et al.  Analysis of retrieved polymer fiber based replacements for the ACL. , 2000, Biomaterials.

[21]  R. Langer,et al.  Cytotoxicity testing of poly(anhydride-co-imides) for orthopedic applications. , 1995, Journal of biomedical materials research.

[22]  M Browne,et al.  Use of Bone Morphogenetic Protein-2 in the Rabbit Ulnar Nonunion Model , 1996, Clinical orthopaedics and related research.

[23]  D. W. Jackson,et al.  Biologic and synthetic implants to replace the anterior cruciate ligament. , 1994, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[24]  Cato T Laurencin,et al.  Bioreactor-based bone tissue engineering: the influence of dynamic flow on osteoblast phenotypic expression and matrix mineralization. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[25]  J. Wozney,et al.  Bone Formation with Use of rhBMP-2 (Recombinant Human Bone Morphogenetic Protein-2)* , 1997, The Journal of bone and joint surgery. American volume.

[26]  K. Skutnabb,et al.  Biologic anchorage of cruciate ligament prosthesis. Bone ingrowth and fixation of the Gore-Tex ligament in sheep. , 1993, Acta orthopaedica Scandinavica.

[27]  D. Wise,et al.  Bioresorbable bone graft substitutes of different osteoconductivities: a histologic evaluation of osteointegration of poly(propylene glycol-co-fumaric acid)-based cement implants in rats. , 2000, Biomaterials.

[28]  Cato T Laurencin,et al.  Tissue engineered microsphere-based matrices for bone repair: design and evaluation. , 2002, Biomaterials.

[29]  H R Allcock,et al.  A highly porous 3-dimensional polyphosphazene polymer matrix for skeletal tissue regeneration. , 1996, Journal of biomedical materials research.

[30]  H R Allcock,et al.  Use of polyphosphazenes for skeletal tissue regeneration. , 1993, Journal of biomedical materials research.

[31]  H. Plenk,et al.  Experimental mechanical and histologic evaluation of the Kennedy ligament augmentation device. , 1985, Clinical orthopaedics and related research.

[32]  Cato T Laurencin,et al.  Tissue engineered bone: measurement of nutrient transport in three-dimensional matrices. , 2003, Journal of biomedical materials research. Part A.

[33]  R. Langer,et al.  In vitro bone biocompatibility of poly(anhydride‐co‐imides) containing pyromellitylimidoalanine , 1996, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[34]  S. F. El-Amina,et al.  Extracellular matrix production by human osteoblasts cultured on biodegradable polymers applicable for tissue engineering , 2002 .

[35]  C T Laurencin,et al.  Tissue engineered bone-regeneration using degradable polymers: the formation of mineralized matrices. , 1996, Bone.

[36]  T. Whitesides,et al.  Orthopaedic Basic Science. Biology and Biomechanics of the Musculoskeletal System. 2nd ed. , 2001 .

[37]  P. Ma,et al.  Porous poly(L-lactic acid)/apatite composites created by biomimetic process. , 1999, Journal of biomedical materials research.

[38]  C T Laurencin,et al.  Tissue-engineered bone formation in vivo using a novel sintered polymeric microsphere matrix. , 2004, The Journal of bone and joint surgery. British volume.

[39]  Cato T Laurencin,et al.  Human osteoblast-like cells in three-dimensional culture with fluid flow. , 2003, Biorheology.

[40]  Fergal J. O'Brien,et al.  Tissue Engineering for Orthopaedic Applications , 2006 .

[41]  P. Hauschka,et al.  Characterization of human bone cells in culture , 1985, Calcified Tissue International.

[42]  Cato T Laurencin,et al.  In vitro bone formation using muscle-derived cells: a new paradigm for bone tissue engineering using polymer-bone morphogenetic protein matrices. , 2003, Biochemical and biophysical research communications.

[43]  C. Laurencin,et al.  Structural and human cellular assessment of a novel microsphere-based tissue engineered scaffold for bone repair. , 2003, Biomaterials.

[44]  L. Yahia Ligaments and Ligamentoplasties , 2011, Springer Berlin Heidelberg.

[45]  K. Stürmer,et al.  Interface and biocompatibility of polyethylene terephthalate knee ligament prostheses A histological and ultrastructural device retrieval analysis in failed synthetic implants used for surgical repair of anterior cruciate ligaments , 2004, Archives of Orthopaedic and Trauma Surgery.

[46]  C T Laurencin,et al.  Three-dimensional degradable porous polymer-ceramic matrices for use in bone repair. , 1996, Journal of biomaterials science. Polymer edition.

[47]  T. He,et al.  Gene therapy for spinal fusion. , 2005, The spine journal : official journal of the North American Spine Society.

[48]  P Ducheyne,et al.  Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function. , 1999, Biomaterials.

[49]  P. Ducheyne Bioglass coatings and bioglass composites as implant materials. , 1985, Journal of biomedical materials research.

[50]  T. Kokubo,et al.  Differences of bone bonding ability and degradation behaviour in vivo between amorphous calcium phosphate and highly crystalline hydroxyapatite coating. , 1996, Biomaterials.

[51]  Cato T Laurencin,et al.  Three-dimensional, bioactive, biodegradable, polymer-bioactive glass composite scaffolds with improved mechanical properties support collagen synthesis and mineralization of human osteoblast-like cells in vitro. , 2003, Journal of biomedical materials research. Part A.

[52]  C T Laurencin,et al.  Bone tissue engineering in a rotating bioreactor using a microcarrier matrix system. , 2001, Journal of biomedical materials research.

[53]  Sheldon R. Simon,et al.  Orthopaedic basic science : biology and biomechanics of the musculoskeletal system , 2000 .

[54]  B Kerebel,et al.  Transformation of biphasic calcium phosphate ceramics in vivo: ultrastructural and physicochemical characterization. , 1989, Journal of biomedical materials research.

[55]  U. Ripamonti Osteoinduction in porous hydroxyapatite implanted in heterotopic sites of different animal models. , 1996, Biomaterials.

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

[57]  C T Laurencin,et al.  Poly(lactide-co-glycolide)/hydroxyapatite delivery of BMP-2-producing cells: a regional gene therapy approach to bone regeneration. , 2001, Biomaterials.

[58]  Aldo R Boccaccini,et al.  Bioactive composite materials for tissue engineering scaffolds , 2005, Expert review of medical devices.

[59]  D. Bonnell,et al.  Initial events at the bioactive glass surface in contact with protein-containing solutions. , 2000, Journal of biomedical materials research.