In situ bone regeneration of large cranial defects using synthetic ceramic implants with a tailored composition and design

Abstract

The repair of large cranial defects with bone is a major clinical challenge that necessitates novel materials and engineering solutions. Three-dimensionally (3D) printed bioceramic (BioCer) implants consisting of additively manufactured titanium frames enveloped with CaP BioCer or titanium control implants with similar designs were implanted in the ovine skull and at s.c. sites and retrieved after 12 and 3 mo, respectively. Samples were collected for morphological, ultrastructural, and compositional analyses using histology, electron microscopy, and Raman spectroscopy. Here, we show that BioCer implants provide osteoinductive and microarchitectural cues that promote in situ bone regeneration at locations distant from existing host bone, whereas bone regeneration with inert titanium implants was confined to ingrowth from the defect boundaries. The BioCer implant promoted bone regeneration at nonosseous sites, and bone bonding to the implant was demonstrated at the ultrastructural level. BioCer transformed to carbonated apatite in vivo, and the regenerated bone displayed a molecular composition indistinguishable from that of native bone. Proof-of-principle that this approach may represent a shift from mere reconstruction to in situ regeneration was provided by a retrieved human specimen, showing that the BioCer was transformed into well-vascularized osteonal bone, with a morphology, ultrastructure, and composition similar to those of native human skull bone.

Monocytes and pyrophosphate promote mesenchymal stem cell viability and early osteogenic differentiation

“…The latter finding is also of clinical interest, emphasizing the important role of the initial inflammatory response after surgery and material implantation for triggering the subsequent regenerative processes. In addition, there is mounting evidence that calcium pyrophosphate can enhance bone formation in vivo when mixed with calcium phosphate cement [16,28]. We have demonstrated two mechanisms that may contribute to this phenomenon.…”

“…The physiological impact of this finding is that PPi may prolong the survival of recruited monocytes, thereby altering both the duration and magnitude of inflammatory signaling. These observations indicate that the role of monocytes and macrophages during bone regeneration induced by pyrophosphate-containing bone ceramics [16,17,28] should be explored.…”

“…Instead, pyrophosphate-containing materials [17] and coatings [26,27] have been shown to promote osteogenic effects. Recently, pyrophosphate-containing bioceramics were shown to considerably promote bone regeneration in osseous and nonosseous sites [28]. Histological evidence revealed that the pyrophosphate-containing bioceramic induces the differentiation of MSCs to osteoblastic cells in parallel to macrophage accumulation in the vicinity of the implant and bone-forming osteoblasts.…”

A Comparative Analysis of PMMA Versus CaP Titanium-Enhanced Implants for Cranioplasty After Decompressive Craniectomy

“…Uncertainty persists regarding the implications of the timing of CP in terms of complication rates and potential bene ts [2,3,35,39]. Materials for reconstruction of cranial defect ideally provide osteoinductive and osteoconductive properties to promote structural and functional restoration [25]. Autologous bone ap reinsertion is common after hemicraniectomy.…”

Guided bone tissue regeneration using a hollow calcium phosphate based implant in a critical size rabbit radius defect

“…However, all calcium phosphate materials do not behave in the same manner, and therefore large efforts have been carried out to optimize properties such as phase composition, substitute ions, porosity, drug delivery and implant design [8][9][10]. Recently, a particular calcium phosphate formulation containing monetite, β-tricalcium phosphate (β-TCP) and β-calcium pyrophosphate (β-CCP) has demonstrated promising bone regenerating properties in vivo [11][12][13][14][15]. The formulation was developed for use in a solid mosaic-scaffold for patients with severe skull defects, in which it was shown that vascularized bone covered the material after 50 months [11,12].…”