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Calcium ions and osteoclastogenesis initiate the induction of bone formation by coral-derived macroporous constructs.

Klar RM, Duarte R, Dix-Peek T, Dickens C, Ferretti C, Ripamonti U - J. Cell. Mol. Med. (2013)

Bottom Line: Osteoclastic inhibition yielded minimal, if any, bone formation by induction. 7% HA/CC pre-loaded with the Ca(++) channel blocker verapamil hydrochloride strongly inhibited the induction of bone formation.Down-regulation of bone morphogenetic protein-2 (BMP-2) together with up-regulation of Noggin genes correlated with limited bone formation in 7% HA/CC pre-loaded with either verapamil or zoledronate, indicating that the induction of bone formation by coral-derived macroporous constructs is via the BMPs pathway.The spontaneous induction of bone formation is initiated by a local peak of Ca(++) activating stem cell differentiation and the induction of bone formation.

View Article: PubMed Central - PubMed

Affiliation: Bone Research Laboratory, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

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Untreated control 7% HA/CC coral-derived macroporous constructs on days 15 and 60 after heterotopic intramuscular implantation. Macroporous self-inducing geometric cues of untreated coral-derived biomimetic constructs induce angiogenesis with capillary sprouting and invasion, cellular trafficking, pattern formation and the morphogenesis of collagenous condensations attached to the macroporous surfaces facing a highly vascular penetrating mesenchymal tissue (magenta arrows in A–C) as early as 15 days after intramuscular implantation. By day 60 (D–H), there are further remodelling and tissue patterning with the induction of bone formation (dark blue arrows). Bone preferentially forms by induction within concavities of the 7% HA/CC macroporous constructs (dark blue arrows in F, H, K and L). Newly formed bone by induction with embedded osteocytes is tightly connected to the implanted biomatrix (I–L); the newly induced bone matrix is surfaced by plump contiguous secreting osteoblasts facing a highly angiogenic mesenchymal supporting matrix (dark blue arrows in K and L). Note how capillary basement membranes touch osteoblastic cells lining newly formed bone within concavities of the substratum (large arrow in L). (Decalcified sections cut at 4 μm stained with Goldner's trichrome).
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fig02: Untreated control 7% HA/CC coral-derived macroporous constructs on days 15 and 60 after heterotopic intramuscular implantation. Macroporous self-inducing geometric cues of untreated coral-derived biomimetic constructs induce angiogenesis with capillary sprouting and invasion, cellular trafficking, pattern formation and the morphogenesis of collagenous condensations attached to the macroporous surfaces facing a highly vascular penetrating mesenchymal tissue (magenta arrows in A–C) as early as 15 days after intramuscular implantation. By day 60 (D–H), there are further remodelling and tissue patterning with the induction of bone formation (dark blue arrows). Bone preferentially forms by induction within concavities of the 7% HA/CC macroporous constructs (dark blue arrows in F, H, K and L). Newly formed bone by induction with embedded osteocytes is tightly connected to the implanted biomatrix (I–L); the newly induced bone matrix is surfaced by plump contiguous secreting osteoblasts facing a highly angiogenic mesenchymal supporting matrix (dark blue arrows in K and L). Note how capillary basement membranes touch osteoblastic cells lining newly formed bone within concavities of the substratum (large arrow in L). (Decalcified sections cut at 4 μm stained with Goldner's trichrome).

Mentions: Digital iconographic images of 7% HA/CC untreated control are presented in Figure 2, at 15 and 60 days, and Figure 5, at 90 days. At harvest, all implants were firmly attached to the ventral fascia and the surrounding rectus abdominis muscle. On day 15, the most peripheral macroporous spaces were invaded by a highly vascular connective tissue matrix (Fig. 2A–C). Vascular invasion and capillary sprouting was pronounced in all treatment modalities. Previous experiments in the non-human primate P. ursinus have shown that the specific geometry and surface characteristics of the coral-derived substratum are conducive to rapid vessels ingrowths’ and capillary sprouting within the early mesenchyme penetrating the macroporous spaces 3.


Calcium ions and osteoclastogenesis initiate the induction of bone formation by coral-derived macroporous constructs.

Klar RM, Duarte R, Dix-Peek T, Dickens C, Ferretti C, Ripamonti U - J. Cell. Mol. Med. (2013)

Untreated control 7% HA/CC coral-derived macroporous constructs on days 15 and 60 after heterotopic intramuscular implantation. Macroporous self-inducing geometric cues of untreated coral-derived biomimetic constructs induce angiogenesis with capillary sprouting and invasion, cellular trafficking, pattern formation and the morphogenesis of collagenous condensations attached to the macroporous surfaces facing a highly vascular penetrating mesenchymal tissue (magenta arrows in A–C) as early as 15 days after intramuscular implantation. By day 60 (D–H), there are further remodelling and tissue patterning with the induction of bone formation (dark blue arrows). Bone preferentially forms by induction within concavities of the 7% HA/CC macroporous constructs (dark blue arrows in F, H, K and L). Newly formed bone by induction with embedded osteocytes is tightly connected to the implanted biomatrix (I–L); the newly induced bone matrix is surfaced by plump contiguous secreting osteoblasts facing a highly angiogenic mesenchymal supporting matrix (dark blue arrows in K and L). Note how capillary basement membranes touch osteoblastic cells lining newly formed bone within concavities of the substratum (large arrow in L). (Decalcified sections cut at 4 μm stained with Goldner's trichrome).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4117557&req=5

fig02: Untreated control 7% HA/CC coral-derived macroporous constructs on days 15 and 60 after heterotopic intramuscular implantation. Macroporous self-inducing geometric cues of untreated coral-derived biomimetic constructs induce angiogenesis with capillary sprouting and invasion, cellular trafficking, pattern formation and the morphogenesis of collagenous condensations attached to the macroporous surfaces facing a highly vascular penetrating mesenchymal tissue (magenta arrows in A–C) as early as 15 days after intramuscular implantation. By day 60 (D–H), there are further remodelling and tissue patterning with the induction of bone formation (dark blue arrows). Bone preferentially forms by induction within concavities of the 7% HA/CC macroporous constructs (dark blue arrows in F, H, K and L). Newly formed bone by induction with embedded osteocytes is tightly connected to the implanted biomatrix (I–L); the newly induced bone matrix is surfaced by plump contiguous secreting osteoblasts facing a highly angiogenic mesenchymal supporting matrix (dark blue arrows in K and L). Note how capillary basement membranes touch osteoblastic cells lining newly formed bone within concavities of the substratum (large arrow in L). (Decalcified sections cut at 4 μm stained with Goldner's trichrome).
Mentions: Digital iconographic images of 7% HA/CC untreated control are presented in Figure 2, at 15 and 60 days, and Figure 5, at 90 days. At harvest, all implants were firmly attached to the ventral fascia and the surrounding rectus abdominis muscle. On day 15, the most peripheral macroporous spaces were invaded by a highly vascular connective tissue matrix (Fig. 2A–C). Vascular invasion and capillary sprouting was pronounced in all treatment modalities. Previous experiments in the non-human primate P. ursinus have shown that the specific geometry and surface characteristics of the coral-derived substratum are conducive to rapid vessels ingrowths’ and capillary sprouting within the early mesenchyme penetrating the macroporous spaces 3.

Bottom Line: Osteoclastic inhibition yielded minimal, if any, bone formation by induction. 7% HA/CC pre-loaded with the Ca(++) channel blocker verapamil hydrochloride strongly inhibited the induction of bone formation.Down-regulation of bone morphogenetic protein-2 (BMP-2) together with up-regulation of Noggin genes correlated with limited bone formation in 7% HA/CC pre-loaded with either verapamil or zoledronate, indicating that the induction of bone formation by coral-derived macroporous constructs is via the BMPs pathway.The spontaneous induction of bone formation is initiated by a local peak of Ca(++) activating stem cell differentiation and the induction of bone formation.

View Article: PubMed Central - PubMed

Affiliation: Bone Research Laboratory, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Show MeSH
Related in: MedlinePlus