Case ReportOsteointegration in Custom-made Porous Hydroxyapatite Cranial Implants: From Reconstructive Surgery to Regenerative Medicine
Introduction
Bone tissue regeneration is an important challenge in the field of orthopedic and craniofacial surgery. Due to the increasing need of clinical solutions able to recover the functional properties of missing or diseased bone, the past implants design is increasingly evolving into scaffolds intended to sustain and assist extensive cell colonization and anchorage to the existing bone, finally leading to osteointegration, which also allows the bone/biomaterial construct to gather biomechanical competence 3, 17.
To do this, regenerative bone scaffolds must exhibit good biocompatibility without inducing inflammation or toxic reactions and exchange suitable chemical signals with the surrounding extracellular matrix in order to activate and promote the series of events at the cell level, thus triggering the formation and organization of new bone tissue (13). In this respect, the first interactions between the cells and the scaffold surface define the quality of the tissue implant interface, which is a key issue for the regenerative ability of the bio-device. The implantation of a three-dimensional (3D) porous scaffold is required, with characteristics of bioactivity and osteoconductivity associated to bio-mechanic performance suitable for the specific implant site 1, 15. More specifically, scaffolds have to provide the space for new bone formation and the necessary support for cells to proliferate and maintain their differential function. Moreover, they should exhibit suitable architectures for inducing the formation and maturation of well-organized tissue (2).
In an attempt to find a balance among composition, structure, porosity, and mechanical strength, biomedical engineers and material scientists developed many different approaches to create structures with open and interconnected pores by imposing different geometries or by forming complex microstructures through the use of natural templates.
Pore volume and size, both at the macroscopic and the microscopic level, are important morphological properties of a scaffold for bone regeneration 7, 10, 11. Macroscopic porosity (i.e., several hundreds of μm), which promotes activation and enhancement of bone ingrowth and osteointegration of the implant after surgery, should also be interconnected with channel-like microporosity that enables fluid exchange throughout the whole scaffold, thus providing a supply of nutrients and the elimination of metabolic waste products. The pore interconnection in a bone scaffold is relevant to avoid a spatially discontinuous ingrowth of the new bone with the formation of bone islands throughout the whole scaffold.
A preclinical study on an animal model implanted with porous HA devices has been recently published by Martini et al (10). The in vivo assessment of this prosthetic device with functions of cranial bone substitute made of porous HA showed the actual capacity of osteointegration of the device with the margins of the host bone and the capability of the device to be hosted by the newly formed bone over time.
The osteointegration process of porous HA device in human patients has been described particularly in the proximity of the bone/implant interface (6). This also affects the mechanical performance of the bone/implant construct. Spontaneous healing of fractured HA devices has been shown, indicating that viable bone and cells had fully colonized the implants (16). In recent years, the behavior of the CustomBone HA prosthesis in humans has also been characterized in 57-year-old and 69-year-old women 5, 12. In both cases the etiology of craniotomy was meningioma, and HA prostheses were explanted because of tumor relapse and subsequent cranioplasty with back-up CustomBone used to repair skull defect. Explantations occurred 3 years and 1 year, respectively, after CustomBone implant. Histological results detected the presence of newly formed bone on the inner perimeter and internal pores of the prostheses. These were the first reported human cases of effective bone-HA integration, but the etiology of treatment, meningioma, should leave open questions about potential tumor infiltration capability.
Here we report two cases of patients who were implanted with custom-made bioceramic porous hydroxyapatite prosthesis after cranial decompression. Both patients experienced postoperative wound complications that required removal of the cranial prosthesis. Both cases subsequently underwent cranial repair using back-up custom-made devices. One patient also went through an intervention of back-up prosthesis removal. To evaluate quantitatively and qualitatively the ossification of HA prosthesis before explantation, computed tomography (CT) scans were carried out. Finally, the three explants obtained from two different patients were analyzed microtomographically and histologically.
Section snippets
Surgical Procedures
Each implant was placed according to the standard manufacturer protocol and as described by Staffa et al. (16). Bone margins were freshened in order to guarantee the maximum contact between the device and cranium. Dural substitutes or growth factors were not used.
Radiological Analysis and Hounsfield Measures
Postoperative CT scans were performed to evaluate implant positioning and margin adhesion. Further radiologic evaluations on bone/implant density were performed using Mimics software (Mimics Innovation Suite v17.0 Medical, Materialise,
Radiologic Evaluation (Positioning, Hounsfield Values at Bone-Implant Margin)
The radiological examination confirmed that the correct position (Figure 1A) of the cranial bone substitute in the implant was maintained over time and that HA implant was completely merged with the host bone. The Hounsfield bone density graph showed a continuity between the implant and host bone: The implant bone density (Hounsfield unit value above 2000 HU) was higher than the host bone density (400–1000 HU) without values below bone threshold (Figure 1B). We also excluded the formation of
Discussion
The aim of the study was to evaluate the repair trend and the osteointegration of custom-made porous HA implants for cranioplasty. Radiological, microtomographical, and histological analyses were performed on two patients who underwent surgical explantation of cranial implants after postoperative complication.
The search for osteointegration using inorganic bone substitutes in cranioplasty should be considered useless because cranial repair is mainly considered a replacement of cranial voids
Acknowledgement
Dr. Fricia and Dr. Passanisi performed the surgeries and collected the clinical cases. Histological and microtomographical analysis were performed at Rizzoli Orthopaedic Institute.
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Design of customized implants and 3D printing of symmetric and asymmetric cranial cavities
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2021, NeurochirurgieCitation Excerpt :These adverse events led to hospitalization extension for 5 patients (4.5%, p = 0.02) and revision surgery for 1 patient (p = 0.02). The CUSTOMBONE device is supported by a growing number of scientific projects concerning implanted patients both adults and children [15–29] demonstrating the clinical performance and reliability of the device in craniofacial procedures. For many years, series and reviews of the literature have multiplied to study and compare cranioplasty implants; whether they be made of titanium, poly-methyl-methacrylate (PMMA), polyetheretherketone (PEEK), autologous bone or hydroxyapatite (25 articles in 2000 to 168 in 2017) [30,31].
Influence of electrochemical parameters on the characteristics of sono-electrodeposited calcium phosphate-coated carbon fiber cloth
2020, Surface and Coatings TechnologyCitation Excerpt :The choice of specific CaP-derived biomaterial depends on the targeted applications. For example, biocompatible ceramics, such as stoichiometric hydroxyapatite (HA) or biphasic calcium phosphate (BCP), are used as commercial bone substitutes [13–21]. In view of the brittleness of CaP ceramics, organic-inorganic composite CaP-derived materials such as chitosan-reinforced calcium phosphate cements [22] or apatite-collagen nanocomposites [23,24] have also been introduced to improve the mechanical properties of the device [25–31].
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2019, International Journal of Non-Linear MechanicsCranioplasty with Porous Hydroxyapatite Custom-Made Bone Flap: Results from a Multicenter Study Enrolling 149 Patients Over 15 Years
2019, World NeurosurgeryCitation Excerpt :The above differences may reflect the different characteristics of the implanted materials: bioinertia (such as in titanium, which offers direct contact with bone tissue), biotolerance (such as in polyether ether ketone or polymethyl methacrylate, which create fibrous tissue at the interface with bone), and bioactivity (such as in autologous graft or PHA, which induces osseointegration by chemical bonding of bone tissue with the implant). In 2015, Fricia et al.34 demonstrated bony cell colonization of the graft in a 2-year histologic analysis of PHA CP with newly formed bone remarking PHA bony-induction capacity. In our series, we had an infection rate of 6.7%, of which 4.8% of patients required surgical revision.
Long-Term Follow-Up Comparative Study of Hydroxyapatite and Autologous Cranioplasties: Complications, Cosmetic Results, Osseointegration
2018, World NeurosurgeryCitation Excerpt :The animal study of the CB prosthesis demonstrated a colonization of the pores by bone cells, spreading from the periphery toward the center of the implant over 12 months, with only very partial resorption.24 Only isolated clinical case reports have described osseointegration limited to partial colonization of the pores, insufficient to ensure adequate resistance.11,15,22,24,25,30,31 To date, there is no validated method to assess the osseointegration of CB prostheses in patients.
Supplementary digital content available online.
Conflict of interest statement: The authors declare that they have no conflicts of interest.