Tissue engineering bone formation in novel recombinant human bone morphogenic protein 2-atelocollagen composite scaffolds.
BACKGROUND
Bone morphogenic proteins (BMPs) are important bone-induction factors, and the development of a suitable carrier for BMPs is a critical step to achieve osteoinductive function. The aims of the present study were to evaluate, at the cellular and molecular levels, the feasibility of recombinant human BMP-2 (rhBMP-2)-collagen composite scaffold and its efficiency for carrying BMP-2 in ectopic bone formation in rats.


METHODS
Scaffolds with (test) or without rhBMP-2 (control) were made and implanted into the calf muscle of 16 5-week-old rats. The tissue responses to the scaffolds were examined by histology. Masson's trichrome and von Kossa stainings were performed to examine collagen matrix deposition and calcification at 3, 7, 10, and 14 days. Expressions of bone phenotypic markers, alkaline phosphatase, osteocalcin, osteopontin, and bone sialoprotein were detected by reverse transcription-polymerase chain reaction and immunohistochemistry.


RESULTS
No detectable adverse responses were noted around the implanted scaffolds, and the area of the resorbed scaffold had been replaced by young connective tissue by 3 to 7 days in both groups. In the rhBMP-2 composite scaffold, collagen matrix deposition was found in the implanted site on day 7 and initial signs of endochondral differentiation also appeared. Mineralization and the expressions of key bone proteins were demonstrated in chondroblasts and osteoblasts at 7 to 14 days. Molecular cascades of bone induction were not shown in control specimens.


CONCLUSIONS
The rhBMP-2-atelocollagen scaffold showed excellent biocompatibility and possessed a bone-inducing capacity in rat within 2 weeks, and, thus, may provide a potential application in tissue engineering of bone tissue.
Hou
Lein-Tuan
LT
Graduate Institute of Clinical Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan. lthou@ha.mc.ntu.edu.tw
Liu
Cheng-Meei
CM
Liu
Bu-Yuan
BY
Chang
Po-Chun
PC
Chen
Min-Huei
MH
Ho
Ming-Hua
MH
Jehng
Su-Min
SM
Liu
Hwa-Chang
HC
D020341:Absorbable Implants; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D020219:Chondrogenesis; D003094:Collagen; D004337:Drug Carriers; D005240:Feasibility Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D020007:Implants, Experimental; D058574:Integrin-Binding Sialoprotein; D010006:Osteoblasts / Q000378:metabolism; D015675:Osteocalcin / Q000096:biosynthesis; D010012:Osteogenesis; D053495:Osteopontin / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000096:biosynthesis; D023822:Tissue Engineering / Q000379:methods*; D016212:Transforming Growth Factor beta
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; C546871:IBSP protein, human; C546873:Ibsp protein, rat; D058574:Integrin-Binding Sialoprotein; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D016212:Transforming Growth Factor beta; C059821:atelocollagen; C499469:recombinant human bone morphogenetic protein-2; D015675:Osteocalcin; D053495:Osteopontin; D003094:Collagen