Guiding bone formation using semi‐onlay calcium phosphate implants in an ovine calvarial model

Abstract

The restoration of cranio‐maxillofacial deformities often requires complex reconstructive surgery in a challenging anatomical region, with abnormal soft tissue structures and bony deficits. In this proof‐of‐concept, the possibility of vertical bone augmentation was explored by suspending hemispherically shaped titanium‐reinforced porous calcium phosphate (CaP) implants (n = 12) over the frontal bone in a sheep model (n = 6). The animals were euthanized after week 13 and the specimens were subject to micro‐computed tomography (μCT) and comprehensive histological analysis. Histology showed that the space between implant and the recipient bone was filled with a higher percentage of newly formed bone (NFB) versus soft tissue with a median of 53% and 47%, respectively. Similar results were obtained from the μ‐CT analysis, with a median of 56% NFB and 44% soft tissue filling the void. Noteworthy, significantly higher bone‐implant contact was found for the CaP (78%, range 14%–94%) versus the Titanium (29%, range 0%–75%) portion of the implant exposed to the surrounding bone. The histological analysis indicates that the CaP replacement by bone is driven by macrophages over time, emphasized by material‐filled macrophages found in close vicinity to the CaP with only a small number of single osteoclasts found actively remodeling the NFB. This study shows that CaP based implants can be assembled with the help of additive manufacturing to guide vertical bone formation without decortification or administration of growth factors. Furthermore, it highlights the potential disadvantage of a seamless fit between the implant and the recipient's bone.

Bone formation beyond the skeletal envelope using calcium phosphate granules packed into a collagen pouch—a pilot study

“…Furthermore, given the large number of CaP-filled macrophages and very low numbers of osteoclasts observed in this current study, it seems that CaP resorption is mainly macrophage-driven. This is consistent with the findings of recent studies which was reported the presence of CaP particles in macrophages after 12, 13, and 52 weeks following implantation in calvarial sheep models of similar CaP composition [28,56,57].…”

“…Depending on their polarization [49] (M1 or M2), macrophages are in fact involved in each phase of the process, i.e. : (1) by cleaning up damaged tissue at the peri-implant area immediately after clot formation [16,50] (2) by initiating tissue reorganization through large enzyme production (3) by inducing [28] bone formation through the secretion of growth hormones such as transforming growth factors, fibroblast growth factors, epithelial growth factors, or also bone morphogenic proteins [48], all involved in recruitment and differentiation of osteogenic cell lines [42,48,51,52] (4) by supporting tissue neovascularization via the secretion of angiogenic molecules [49,50,53,54] and finally (5) by playing a prominent role in the biodegradation of materials [55]. Furthermore, given the large number of CaP-filled macrophages and very low numbers of osteoclasts observed in this current study, it seems that CaP resorption is mainly macrophage-driven.…”

“…The phase compositions of the intact CaP granules samples were determined using x-ray diffraction (XRD; Aeris Panalytical, Malvern) on two samples (n = 2) with a theta-theta (2θ) setup with Nifiltered Cu-K irradiation and Rietveld refinement, as described previously [28]. The diffraction patterns were collected with a beam knife between 2θ of 10 • -60 • and a step of 0.011 • and 21.5 s. Rietveld refinements were applied to perform a quantitative phase composition analysis with HighScore Plus [29].…”

Human Whole Blood Interactions with Craniomaxillofacial Reconstruction Materials: Exploring In Vitro the Role of Blood Cascades and Leukocytes in Early Healing Events

“…A considerable presence of osteoblasts has been observed at early and late stages in preclinical models. Interestingly, minimal osteoclast activity was observed [19,20,[46][47][48]; instead, a moderate to substantial presence of material-filled macrophages was observed, which are also responsive to the complement proteins C3a, C5a, and bradykinin [49]. Contrarily, titanium meshes [19], solid titanium implants, and PEEK have been found to trigger a foreign body reaction, leading to chronic inflammation that promotes fibrous encapsulation rather than bone formation [19,25,50].…”

“…A macro contact angle meter (DM-CE1, Kyowa, Japan) with appropriate software (FAMAS, Kyowa, Japan) was used to perform the wettability tests and calculate the contact angles. The contact angle (θ) was defined as the angle between the solid phase and the liquid phase as described [20]. Prior to the contact angle experiments all materials were cleaned in water and dried in a desiccator.…”