Abstract
Coral-derived calcium carbonate/hydroxyapatite macroporous constructs of the genus Goniopora with limited hydrothermal conversion to hydroxyapatite (7% HA/CC) initiate the induction of bone formation. Which are the molecular signals that initiate pattern formation and the induction of bone formation? To evaluate the role of released calcium ions and osteoclastogenesis, 7% HA/CC was pre-loaded with either 500 μg of the calcium channel blocker, verapamil hydrochloride, or 240 μg of the osteoclast inhibitor, biphosphonate zoledronate, and implanted in the rectus abdominis muscle of six adult Chacma baboons Papio ursinus. Generated tissues on days 15, 60 and 90 were analysed by histomorphometry and qRT-PCR. On day 15, up-regulation of type IV collagen characterized all the implanted constructs correlating with vascular invasion. Zoledronate-treated specimens showed an important delay in tissue patterning and morphogenesis with limited bone formation. 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.
Highlights
The future of the continuing evolution of biomaterials [1] is to functionalize the implanted biomaterials surfaces by activating the surface biology to directly induce specific molecular and tissue biology phenomena initiating regenerative responses as inductive biomaterials [2,3,4,5,6,7,8,9,10,11,12]
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]
The future of the continuing evolution of biomaterials [1] is to functionalize the implanted biomaterials’ surfaces to evoke a pattern of gene expression that invocates selected tissue biology and morphological cascades [3, 6, 10, 25]. Such novel biomaterials when interacting with multipotent pleiotropic stem cells ‘niches’ induce specific molecular and tissue biology phenomena initiating regenerative responses as inductive biomaterials [2, 3, 6, 25]
Summary
The future of the continuing evolution of biomaterials [1] is to functionalize the implanted biomaterials surfaces by activating the surface biology to directly induce specific molecular and tissue biology phenomena initiating regenerative responses as inductive biomaterials [2,3,4,5,6,7,8,9,10,11,12]. The paradigm has been modified by the language of geometry [4,5,6, 12, 22]; a number of systematic studies in heterotopic sites of the Chacma baboon Papio ursinus have shown that the driving force of the intrinsic osteoinductivity by bioactive biomaterial matrices is the shape and surface characteristics of the implanted scaffold [4, 5].
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