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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

Surgical models and implantation designs in the Chacma baboons Papio ursinus for tissue induction and morphogenesis by calcium phosphate-based macroporous constructs implanted in orthotopic calvarial and heterotopic rectus abdominis intramuscular sites. (A) A calvarial Latin square block design resulted in the rotational allocation of macroporous disks of single phase (single phase HA) and biphasic hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) constructs solo or pre-loaded with 25 and 125 μg human transforming growth factor-β3 (hTGF-β3) within a total of 24 calvarial defects in four animals with a balanced distribution between anterior and posterior regions of the calvaria (Ripamonti, 2006a; Ripamonti et al., 2007b). (B–D) Heterotopic intramuscular rectus abdominis model and implantation designs in eight adult Chacma baboons P. ursinus. (B) Heterotopic implantation of 4 disks 25 mm in diameter 3.5/4 mm in thickness and 4 cylinders 12 mm in diameter in 4 P. ursinus for a total of 32 specimens in the rectus abdominis muscle. (C) Intramuscular rectus abdominis implantation of 12 coral-derived calcium carbonate-based macroporous constructs fully converted to hydroxyapatite (100% HA/CC), and partially converted to 5 and 13% hydroxyapatite (5 and 13% HA/CC) pre-loaded with 125 and 250 μg hTGF-β3 implanted in two adult P. ursinus and harvested on day 20. (D) Intramuscular rectus abdominis implantation in two adult P. ursinus of 4 13% and 4 5% partially converted HA/CC constructs pre-loaded with binary applications of hTGF-β3: hOP-1 at 5:1 and 1:5 ratios and harvested on day 30.
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Figure 1: Surgical models and implantation designs in the Chacma baboons Papio ursinus for tissue induction and morphogenesis by calcium phosphate-based macroporous constructs implanted in orthotopic calvarial and heterotopic rectus abdominis intramuscular sites. (A) A calvarial Latin square block design resulted in the rotational allocation of macroporous disks of single phase (single phase HA) and biphasic hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) constructs solo or pre-loaded with 25 and 125 μg human transforming growth factor-β3 (hTGF-β3) within a total of 24 calvarial defects in four animals with a balanced distribution between anterior and posterior regions of the calvaria (Ripamonti, 2006a; Ripamonti et al., 2007b). (B–D) Heterotopic intramuscular rectus abdominis model and implantation designs in eight adult Chacma baboons P. ursinus. (B) Heterotopic implantation of 4 disks 25 mm in diameter 3.5/4 mm in thickness and 4 cylinders 12 mm in diameter in 4 P. ursinus for a total of 32 specimens in the rectus abdominis muscle. (C) Intramuscular rectus abdominis implantation of 12 coral-derived calcium carbonate-based macroporous constructs fully converted to hydroxyapatite (100% HA/CC), and partially converted to 5 and 13% hydroxyapatite (5 and 13% HA/CC) pre-loaded with 125 and 250 μg hTGF-β3 implanted in two adult P. ursinus and harvested on day 20. (D) Intramuscular rectus abdominis implantation in two adult P. ursinus of 4 13% and 4 5% partially converted HA/CC constructs pre-loaded with binary applications of hTGF-β3: hOP-1 at 5:1 and 1:5 ratios and harvested on day 30.

Mentions: For orthotopic calvarial implantation, single phase hydroxyapatite (single phase HA) and biphasic hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) constructs (Council for Scientific and Industrial Research, Materials Science and Manufacturing, Pretoria, South Africa) were sintered into macroporous disks, 25 mm in diameter by 4 mm in thickness (Ripamonti et al., 2007b); the contra-lateral calvarial implantation design for the allocation of the treatment variables is illustrated in Figure 1A.


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

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

Surgical models and implantation designs in the Chacma baboons Papio ursinus for tissue induction and morphogenesis by calcium phosphate-based macroporous constructs implanted in orthotopic calvarial and heterotopic rectus abdominis intramuscular sites. (A) A calvarial Latin square block design resulted in the rotational allocation of macroporous disks of single phase (single phase HA) and biphasic hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) constructs solo or pre-loaded with 25 and 125 μg human transforming growth factor-β3 (hTGF-β3) within a total of 24 calvarial defects in four animals with a balanced distribution between anterior and posterior regions of the calvaria (Ripamonti, 2006a; Ripamonti et al., 2007b). (B–D) Heterotopic intramuscular rectus abdominis model and implantation designs in eight adult Chacma baboons P. ursinus. (B) Heterotopic implantation of 4 disks 25 mm in diameter 3.5/4 mm in thickness and 4 cylinders 12 mm in diameter in 4 P. ursinus for a total of 32 specimens in the rectus abdominis muscle. (C) Intramuscular rectus abdominis implantation of 12 coral-derived calcium carbonate-based macroporous constructs fully converted to hydroxyapatite (100% HA/CC), and partially converted to 5 and 13% hydroxyapatite (5 and 13% HA/CC) pre-loaded with 125 and 250 μg hTGF-β3 implanted in two adult P. ursinus and harvested on day 20. (D) Intramuscular rectus abdominis implantation in two adult P. ursinus of 4 13% and 4 5% partially converted HA/CC constructs pre-loaded with binary applications of hTGF-β3: hOP-1 at 5:1 and 1:5 ratios and harvested on day 30.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Surgical models and implantation designs in the Chacma baboons Papio ursinus for tissue induction and morphogenesis by calcium phosphate-based macroporous constructs implanted in orthotopic calvarial and heterotopic rectus abdominis intramuscular sites. (A) A calvarial Latin square block design resulted in the rotational allocation of macroporous disks of single phase (single phase HA) and biphasic hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) constructs solo or pre-loaded with 25 and 125 μg human transforming growth factor-β3 (hTGF-β3) within a total of 24 calvarial defects in four animals with a balanced distribution between anterior and posterior regions of the calvaria (Ripamonti, 2006a; Ripamonti et al., 2007b). (B–D) Heterotopic intramuscular rectus abdominis model and implantation designs in eight adult Chacma baboons P. ursinus. (B) Heterotopic implantation of 4 disks 25 mm in diameter 3.5/4 mm in thickness and 4 cylinders 12 mm in diameter in 4 P. ursinus for a total of 32 specimens in the rectus abdominis muscle. (C) Intramuscular rectus abdominis implantation of 12 coral-derived calcium carbonate-based macroporous constructs fully converted to hydroxyapatite (100% HA/CC), and partially converted to 5 and 13% hydroxyapatite (5 and 13% HA/CC) pre-loaded with 125 and 250 μg hTGF-β3 implanted in two adult P. ursinus and harvested on day 20. (D) Intramuscular rectus abdominis implantation in two adult P. ursinus of 4 13% and 4 5% partially converted HA/CC constructs pre-loaded with binary applications of hTGF-β3: hOP-1 at 5:1 and 1:5 ratios and harvested on day 30.
Mentions: For orthotopic calvarial implantation, single phase hydroxyapatite (single phase HA) and biphasic hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) constructs (Council for Scientific and Industrial Research, Materials Science and Manufacturing, Pretoria, South Africa) were sintered into macroporous disks, 25 mm in diameter by 4 mm in thickness (Ripamonti et al., 2007b); the contra-lateral calvarial implantation design for the allocation of the treatment variables is illustrated in Figure 1A.

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