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A Macroporous Bioreactor Super Activated by the Recombinant Human Transforming Growth Factor-β(3).

Ripamonti U, Teare J, Ferretti C - Front Physiol (2012)

Bottom Line: Bone formation was assessed on decalcified paraffin-embedded sections by measuring the fractional volume of newly formed bone.On day 30 and 90, single phase HA implants showed greater amounts of bone when compared to biphasic specimens; 5 and 13% HA/CC pre-loaded with 125 and 250 μg hTGF-β(3) showed substantial induction of bone formation; 250 μg hTGF-β(3) induced as yet unreported massive induction of bone formation as early as 20 days prominently outside the profile of the macroporous constructs.The unprecedented tissue induction by single doses of 250 μg hTGF-β(3) resulting in rapid bone morphogenesis of vast mineralized ossicles with multiple trabeculations surfaced by contiguous secreting osteoblasts is the novel molecular and morphological frontier for the induction of bone formation in clinical contexts.

View Article: PubMed Central - PubMed

Affiliation: Bone Research Unit, Faculty of Health Sciences, School of Physiology, Medical Research Council/University of the Witwatersrand Johannesburg, South Africa.

ABSTRACT
Macroporous single phase hydroxyapatite (HA) and biphasic HA/β-tricalcium phosphate with 33% post-sinter hydroxyapatite (HA/β-TCP) were combined with 25 or 125 μg recombinant human transforming growth factor-β3 (hTGF-β(3)) to engineer a super activated bioreactor implanted in orthotopic calvarial and heterotopic rectus abdominis muscle sites and harvested on day 30 and 90. Coral-derived calcium carbonate fully converted (100%) and partially converted to 5 and 13% hydroxyapatite/calcium carbonate (5 and 13% HA/CC) pre-loaded with 125 and 250 μg hTGF-β(3), and 1:5 and 5:1 binary applications of hTGF-β(3): hOP-1 by weight, were implanted in the rectus abdominis and harvested on day 20 and 30, respectively, to monitor spatial/temporal morphogenesis by high doses of hTGF-β(3). Bone formation was assessed on decalcified paraffin-embedded sections by measuring the fractional volume of newly formed bone. On day 30 and 90, single phase HA implants showed greater amounts of bone when compared to biphasic specimens; 5 and 13% HA/CC pre-loaded with 125 and 250 μg hTGF-β(3) showed substantial induction of bone formation; 250 μg hTGF-β(3) induced as yet unreported massive induction of bone formation as early as 20 days prominently outside the profile of the macroporous constructs. The induction of bone formation is controlled by the implanted ratio of the recombinant morphogens, i.e., the 1:5 hTGF-β(3):hOP-1 ratio by weight was greater than the inverse ratio. The unprecedented tissue induction by single doses of 250 μg hTGF-β(3) resulting in rapid bone morphogenesis of vast mineralized ossicles with multiple trabeculations surfaced by contiguous secreting osteoblasts is the novel molecular and morphological frontier for the induction of bone formation in clinical contexts.

No MeSH data available.


Related in: MedlinePlus

Induction of bone formation by orthotopic calvarial biphasic hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) harvested on day 30. (A,B) Low and high power views of untreated HA/β-TCP construct showing bone formation pericranially (light blue arrows) (A) within macroporous spaces (A,B). (C,D) Induction of bone formation within concavities (arrows) of the macroporous spaces of untreated HA/β-TCP constructs; the induction of bone forms exclusively within the concavities of the implanted substratum (blue arrows) (E,F) High power views of macroporous spaces treated with 125 μg hTGF-β3 with multiple osteoblasts surfacing the newly formed bone (dark blue arrows).
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Figure 6: Induction of bone formation by orthotopic calvarial biphasic hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) harvested on day 30. (A,B) Low and high power views of untreated HA/β-TCP construct showing bone formation pericranially (light blue arrows) (A) within macroporous spaces (A,B). (C,D) Induction of bone formation within concavities (arrows) of the macroporous spaces of untreated HA/β-TCP constructs; the induction of bone forms exclusively within the concavities of the implanted substratum (blue arrows) (E,F) High power views of macroporous spaces treated with 125 μg hTGF-β3 with multiple osteoblasts surfacing the newly formed bone (dark blue arrows).

Mentions: Control specimens of biphasic HA/β-TCP showed albeit minimal (Figure 3), the induction of bone formation classically forming within concavities of the macroporous substratum (Figure 6). Newly formed bone protruded within the macroporous spaces covered by numerous contiguous osteoblasts (Figure 6B). On day 30, scattered islands of newly formed woven bone formed in specimens pre-treated with 25 μg TGF-β3 (4.68 ± 3.5%) Figures 6E,F), though bone was not detected in specimens pre-treated with 125 μg TGF-β3 (Figure 3).


A Macroporous Bioreactor Super Activated by the Recombinant Human Transforming Growth Factor-β(3).

Ripamonti U, Teare J, Ferretti C - Front Physiol (2012)

Induction of bone formation by orthotopic calvarial biphasic hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) harvested on day 30. (A,B) Low and high power views of untreated HA/β-TCP construct showing bone formation pericranially (light blue arrows) (A) within macroporous spaces (A,B). (C,D) Induction of bone formation within concavities (arrows) of the macroporous spaces of untreated HA/β-TCP constructs; the induction of bone forms exclusively within the concavities of the implanted substratum (blue arrows) (E,F) High power views of macroporous spaces treated with 125 μg hTGF-β3 with multiple osteoblasts surfacing the newly formed bone (dark blue arrows).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3369251&req=5

Figure 6: Induction of bone formation by orthotopic calvarial biphasic hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) harvested on day 30. (A,B) Low and high power views of untreated HA/β-TCP construct showing bone formation pericranially (light blue arrows) (A) within macroporous spaces (A,B). (C,D) Induction of bone formation within concavities (arrows) of the macroporous spaces of untreated HA/β-TCP constructs; the induction of bone forms exclusively within the concavities of the implanted substratum (blue arrows) (E,F) High power views of macroporous spaces treated with 125 μg hTGF-β3 with multiple osteoblasts surfacing the newly formed bone (dark blue arrows).
Mentions: Control specimens of biphasic HA/β-TCP showed albeit minimal (Figure 3), the induction of bone formation classically forming within concavities of the macroporous substratum (Figure 6). Newly formed bone protruded within the macroporous spaces covered by numerous contiguous osteoblasts (Figure 6B). On day 30, scattered islands of newly formed woven bone formed in specimens pre-treated with 25 μg TGF-β3 (4.68 ± 3.5%) Figures 6E,F), though bone was not detected in specimens pre-treated with 125 μg TGF-β3 (Figure 3).

Bottom Line: Bone formation was assessed on decalcified paraffin-embedded sections by measuring the fractional volume of newly formed bone.On day 30 and 90, single phase HA implants showed greater amounts of bone when compared to biphasic specimens; 5 and 13% HA/CC pre-loaded with 125 and 250 μg hTGF-β(3) showed substantial induction of bone formation; 250 μg hTGF-β(3) induced as yet unreported massive induction of bone formation as early as 20 days prominently outside the profile of the macroporous constructs.The unprecedented tissue induction by single doses of 250 μg hTGF-β(3) resulting in rapid bone morphogenesis of vast mineralized ossicles with multiple trabeculations surfaced by contiguous secreting osteoblasts is the novel molecular and morphological frontier for the induction of bone formation in clinical contexts.

View Article: PubMed Central - PubMed

Affiliation: Bone Research Unit, Faculty of Health Sciences, School of Physiology, Medical Research Council/University of the Witwatersrand Johannesburg, South Africa.

ABSTRACT
Macroporous single phase hydroxyapatite (HA) and biphasic HA/β-tricalcium phosphate with 33% post-sinter hydroxyapatite (HA/β-TCP) were combined with 25 or 125 μg recombinant human transforming growth factor-β3 (hTGF-β(3)) to engineer a super activated bioreactor implanted in orthotopic calvarial and heterotopic rectus abdominis muscle sites and harvested on day 30 and 90. Coral-derived calcium carbonate fully converted (100%) and partially converted to 5 and 13% hydroxyapatite/calcium carbonate (5 and 13% HA/CC) pre-loaded with 125 and 250 μg hTGF-β(3), and 1:5 and 5:1 binary applications of hTGF-β(3): hOP-1 by weight, were implanted in the rectus abdominis and harvested on day 20 and 30, respectively, to monitor spatial/temporal morphogenesis by high doses of hTGF-β(3). Bone formation was assessed on decalcified paraffin-embedded sections by measuring the fractional volume of newly formed bone. On day 30 and 90, single phase HA implants showed greater amounts of bone when compared to biphasic specimens; 5 and 13% HA/CC pre-loaded with 125 and 250 μg hTGF-β(3) showed substantial induction of bone formation; 250 μg hTGF-β(3) induced as yet unreported massive induction of bone formation as early as 20 days prominently outside the profile of the macroporous constructs. The induction of bone formation is controlled by the implanted ratio of the recombinant morphogens, i.e., the 1:5 hTGF-β(3):hOP-1 ratio by weight was greater than the inverse ratio. The unprecedented tissue induction by single doses of 250 μg hTGF-β(3) resulting in rapid bone morphogenesis of vast mineralized ossicles with multiple trabeculations surfaced by contiguous secreting osteoblasts is the novel molecular and morphological frontier for the induction of bone formation in clinical contexts.

No MeSH data available.


Related in: MedlinePlus