Tissue-engineered bone biomimetic to regenerate calvarial critical-sized defects in athymic rats.

A tissue-engineered bone biomimetic device was developed to regenerate calvaria critical-sized defects (CSDs) in athymic rats. Well-documented evidence clearly confirms that left untreated, CSDs will not spontaneously regenerate bone. To accomplish regeneration, four candidate treatments were assessed: porous poly(D,L-lactide) and type I collagen (PLC), PLC and human osteoblast precursor cells (OPCs) at 2 x 10(5) (PLC/OPCs), PLC and 50 microg of recombinant human bone morphogenetic protein-2 (PLC/rhBMP-2), and PLC/OPCs/rhBMP-2 (the bone biomimetic device). The hypotheses for this study were PLC/OPCs/rhBMP-2 would promote more new bone formation in CSDs than the other treatments and the amount of bone formation would be time dependent. To test the hypotheses, outcomes from treatments were measured at 2 and 4 weeks postoperatively by radiomorphometry for percent radiopacity and by histomorphometry for square millimeters of new bone formation. Data were analyzed by analysis of variance and Fisher's protected least significant difference for multiple comparisons with p < or = 0.05. At 2 and 4 weeks, radiomorphometric data revealed PLC/rhBMP-2 and PLC/OPCs/rhBMP-2 promoted significantly more radiopacity than either PLC or PLC/OPCs. Histomorphometry data at 2 and 4 weeks indicated significantly more new bone formation for PLC/rhBMP-2, PLC/OPCs/rhBMP-2, and PLC/OPCs compared to PLC. By 4 weeks, PLC/OPCs/rhBMP-2 and PLC/rhBMP-2 had regenerated the CSDs with more new bone than the other treatments; the quantity of bone at 4 weeks for these treatments was greater than at 2 weeks.

[1]  M. Koutsilieris,et al.  Three‐dimensional type I collagen gel system for the study of osteoblastic metastases produced by metastatic prostate cancer , 1994, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[2]  A. Mikos,et al.  Osteoblast function on synthetic biodegradable polymers. , 1994, Journal of biomedical materials research.

[3]  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.

[4]  J H Brekke,et al.  A rationale for delivery of osteoinductive proteins. , 1996, Tissue engineering.

[5]  P. Sullivan,et al.  Issues and controversies in the management of cleft palate. , 1993, Clinics in plastic surgery.

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

[7]  O. Antonyshyn,et al.  Early Definitive Bone and Soft‐Tissue Reconstruction of Major Gunshot Wounds of the Face , 1991, Plastic and reconstructive surgery.

[8]  J. Hollinger,et al.  Recombinant human bone morphogenetic protein-2 is superior to demineralized bone matrix in repairing craniotomy defects in rats. , 1994, Journal of biomedical materials research.

[9]  R. Marx.  Current advances in reconstruction of the mandible in head and neck cancer surgery. , 1991, Seminars in surgical oncology.

[10]  S. Goldstein,et al.  Stimulation of new bone formation by direct transfer of osteogenic plasmid genes. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[11]  G. Finerman,et al.  Regional gene therapy with a BMP‐2‐producing murine stromal cell line induces heterotopic and orthotopic bone formation in rodents , 1998, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[12]  J. Hollinger.  Factors for osseous repair and delivery: Part II. , 1993, The Journal of craniofacial surgery.

[13]  K. Leong,et al.  Poly(α-hydroxy acids). Carriers for bone morphogenetic proteins , 1996 .

[14]  V. Rosen,et al.  The effects of aging on the bone inductive activity of recombinant human bone morphogenetic protein-2. , 1996, Endocrinology.

[15]  K. Takagi,et al.  The Reaction of the Dura To Bone Morphogenetic Protein (BMP) in Repair of Skull Defects , 1982, Annals of surgery.

[16]  H. Uludaǧ,et al.  Establishing an Immortalized Human Osteoprecursor Cell Line: OPC1 , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[17]  V. Rosen,et al.  Purification and characterization of other distinct bone-inducing factors. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[18]  G. Gillies,et al.  Utilization of type I collagen gel, demineralized bone matrix, and bone morphogenetic protein-2 to enhance autologous bone lumbar spinal fusion. , 1997, Journal of neurosurgery.

[19]  J. Allay,et al.  LacZ and interleukin-3 expression in vivo after retroviral transduction of marrow-derived human osteogenic mesenchymal progenitors. , 1997, Human gene therapy.

[20]  J. Wozney,et al.  Poly(α-hydroxy acid) carrier for delivering recombinant human bone morphogenetic protein-2 for bone regeneration , 1996 .

[21]  Michi Ken-ichi,et al.  The Effect of Aging on the Healing of Hydroxylapatite Implants , 1993 .

[22]  V. Rosen,et al.  Novel regulators of bone formation: molecular clones and activities. , 1988 .

[23]  J. Wozney,et al.  The bone morphogenetic protein family and osteogenesis , 1992, Molecular reproduction and development.

[24]  Jeffrey O. Hollinger,et al.  Chapter III.2 – Options For Engineering Bone , 1998 .

[25]  G. Stein,et al.  The influence of type I collagen on the development and maintenance of the osteoblast phenotype in primary and passaged rat calvarial osteoblasts: modification of expression of genes supporting cell growth, adhesion, and extracellular matrix mineralization. , 1995, Experimental cell research.

[26]  J. Wozney,et al.  Recombinant human bone morphogenetic protein-2 and collagen for bone regeneration. , 1998, Journal of biomedical materials research.

[27]  A. Reddi.  Bone and cartilage differentiation. , 1994, Current opinion in genetics & development.

[28]  V. Rosen,et al.  The BMP proteins in bone formation and repair. , 1992, Trends in genetics : TIG.

[29]  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.

[30]  J O Hollinger,et al.  The critical size defect as an experimental model for craniomandibulofacial nonunions. , 1986, Clinical orthopaedics and related research.

[31]  R. Langer,et al.  Wetting of poly(L-lactic acid) and poly(DL-lactic-co-glycolic acid) foams for tissue culture. , 1994, Biomaterials.

[32]  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.

[33]  Hyun D Kim,et al.  Bone Morphogenetic Protein 2-Coated Porous Poly-L-lactic Acid Scaffolds: Release Kinetics and Induction of Pluripotent C3H10T1/2 Cells , 1998 .