8.1 S UBJECTIVE EVALUATION 8.1.1 Patients’ Survey

8 R ESULTS

8.1 S UBJECTIVE EVALUATION 8.1.1 Patients’ Survey

Intragroup analysis resulting from ANOVA showed that there was not significant difference between the level of pain/discomfort at 2 days and 2 weeks after surgery, but patients indicated the level of pain/discomfort significantly lower at 4 weeks after surgery when compared to 2 days after surgery, even though not significant when compared to 2 weeks after surgery. As regard for the aesthetic improvement, no significant differences were detected from 4 weeks to 12 weeks after surgery, but aesthetic improvement perception was significantly improved 1 year after surgery when compared to 4 weeks after surgery. The results of Pearson correlation analysis between the aesthetic improvement 1 year after surgery and aesthetic improvement according to expectations showed high significant correlation (r=0.89, P<0.05).

VAS score

Question Question n° Mean SD

LEVEL OF PAIN/DISCOMFORT 2 DAYS AFTER SURGERY 1 8.30 2.49 LEVEL OF PAIN/DISCOMFORT 2 WEEKS AFTER SURGERY 2 6.20 3.53 LEVEL OF PAIN/DISCOMFORT 4 WEEKS AFTER SUGERY 3 5.20

1.97 AESTHETIC IMPROVEMENT 4 WEEKS AFTER SURGERY 4 4.90 3.94 AESTHETIC IMPROVEMENT 8 WEEKS AFTER SURGERY 5 7.30 2.59 AESTHETIC IMPROVEMENT 12 WEEKS AFTER SURGERY 6 7.50 2.18 AESTHETIC IMPROVEMENT 1 YEAR AFTER SURGERY 7 8.40

1.56 AESTHETIC IMPROVEMENT ACCORDING TO EXPECTATIONS 8 8.60 1.87

Table 2 Patients’ survey. N = 14. Significant differences (p < 0.05) resulting from ANOVA and post hoc with pairwise comparison analysis for level of pain/discomfort and aesthetic improvement, respectively, are displayed. a Significant compared to Question n°1 (P=0.014) ; b significant compared to Question n°4 (P=0.008).

8.1.2 Surgeons’ Survey

Intragroup analysis resulting from ANOVA showed that there was not significant

difference in the perception of the aesthetic improvement from 4 weeks after surgery to

1 year after surgery. The results of Pearson correlation analysis between the aesthetic

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Question Question

n°

VAS score Mean SD LEVEL OF DIFFICULTY OF SURGERY COMPARED WITH SAME

SURGERY USING TRADITIONAL BONE GRAFT

1 3.55 2.86

LEVEL OF CORRESPONDANCE WITH THE VIRTUAL PLANNING

2 9.03 1.38

AESTHETIC IMPROVEMENT 4 WEEKS AFTER SURGERY 3 8.38 2.44 AESTHETIC IMPROVEMENT 8 WEEKS AFTER SURGERY 4 8.57 1.51 AESTHETIC IMPROVEMENT 12 WEEKS AFTER SURGERY 5 8.99 1.02 AESTHETIC IMPROVEMENT 1 YEAR AFTER SURGERY 6 9.15 1.28 AESTHETIC IMPROVEMENT ACCORDING TO EXPECTATIONS 7 9.05 1.50

Table 3 Surgeons’ survey. N = 11. Significant differences (p < 0.05) resulting from ANOVA and post hoc with pairwise comparison analysis for aesthetic improvement are displayed. No significant differences were found.

8.1.3 Patients versus surgeons perceptions for aesthetic improvement

Comparison between the two groups of respondents for the perception of aesthetic improvement showed significant differences between patients and surgeons perception of aesthetic improvement at 4 weeks and 1 year after surgery. Surgeons, in fact, showed significantly higher aesthetic improvement perception for the considered timepoints when compared to patients’ perception.

Patients (n=14)

Surgeons (n=11)

P

Mean SD Mean SD 0.14

AESTHETIC IMPROVEMENT 4 WEEKS AFTER SURGERY

4.90 3.94 8.38 2.44 0.03

AESTHETIC IMPROVEMENT 8 WEEKS AFTER SURGERY

7.30 2.59 8.57 1.51 0.18

AESTHETIC IMPROVEMENT 12 WEEKS AFTER SURGERY

7.50 2.8 8.99 1.02 0.49

AESTHETIC IMPROVEMENT 1 YEAR AFTER SURGERY

8.40 1.56 9.15 1.28 0.01

AESTHETIC IMPROVEMENT ACCORDING TO EXPECTATIONS

8.60 1.87 9.05 1.50 0.14

Table 4 Patients versus surgeons perceptions for aesthetic improvement. Significant differences (p < 0.05)

resulting from Student-t test comparison for level of aesthetic improvement between patients and surgeons at

the considered timepoints are displayed. * P<0.05.

8.2 O BJECTIVE EVALUATION

The linear measurements of the virtual model and printed model are presented in Table 2. The mean maximum distance of the printed model was significantly smaller than that of the virtual model, with a mean difference of -0.075 mm.

Sintered-Original difference/ 10mm

p-value

Maximum distance -0,075 0,013

Table 5 linear difference

The surface measurements are presented in Tables 3 and and4. Compared to the original model, most surface measurements of the sintered model showed significantly decreased values. The volume ratio measurement of each model was calculated assuming that the volume measurement of the original model was 100%. Compared to the sintered model, the mean volume of the printed model a 1.48% decrease showed a statistically significant change in surface.

Sintered-Original difference /mm2

p-value

Surface mm2 -12,11 0,001

Table 6 surface difference

The comparison of mean deviation measurements with best-fit alignment is presented in Table 5. The mean value of 100,000 point deviations was 0.036 mm.

Sintered-original model p-value Mean deviation (mm() 0.036 (0,004) 0,001

Table 7 volume difference

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9 D ISCUSSION

The aim of the present study was to test the reliability of the workflow to perform custom made bone graft in patients needing craniofacial surgery rehabilitation due to pathological reasons. The second aim of the present study was to test the quality of the custom-made grafts for different categories of respondents, comprising patients and surgeons who performed surgery.

First the virtual model of the custom-made bone graft was modeled on the basis of the pre-treatment imaging (cbct or CT). The error between the virtual planning and the real custom-made titanium model was calculated by linear and surface measurements.

Several parameters might be involved in the accuracy outcome when using laser sintering techniques such as slice thickness when the CAD model is resliced, diameter, angle of the CO

laser beam, type and size of powder particles and direction of fabrication [76].

Previous studies showed mean differences of Ϭ͘ϲϮнͬ-0.35 mm [77] for titanium bone graft. In the present study, the results confirmed previous evidence. Linear measurements on the maximum width showed a difference of less than 1 mm (Table 2) between the virtual model and the sintered model in titanium. The difference does also consider the level of accuracy and error of the 3D scanner employed for the scan of the real model to have the stl file to do the comparison. The superimposition method used was a best fit since no changes occurred between the models [78]. As regard for the linear measurements the difference is largely acceptable from a clinical point of view due to the elasticity of the bone and the capability of the surgeon to adapt the graft, considering the even lower correspondence of the traditional bone allografts to the receiving site [79]. Chang et al.(2003) evaluated the accuracy of the laser sintering technique of three types of bone defects: unilateral maxillectomy, maxillectomy, and orbitomaxillectomy in fresh cadaver skulls[80]. The defects simulated resections of a tumour in the maxillary sinus. Their results showed that mean error was lower than 2 mm, then consistent with the results of the present study.

Together with the linea rmeasurements, the surface measurements revealed encouraging results. They were performed in percentage considering the virtual model as the 100%.

The mean difference was of 1.48% with a smaller surface of the sintered model compared

to the virtual model. The lower correspondances were found on the boundaries of the

model where the main adaptation needed to be performed during the surgery. This

aspect might represent a difficulty in managing this kind of grafts that should be

considered from the beginning of the procedure. Previous studies measured also

percentage of differences and showed as 3DP prototypes have an accuracy around 2% in

replicating bones of the craio-maxillo-facial district. The present investigation showed an

error less than 2% which was clinically acceptable.

The second aim of the present study was the evaluation of quality of surgery and post- treatment outcomes from the patients and the surgeons point of view. Several studies nowadays consider the different point of view of different respondents categories since it was suggested it might improve diagnostic precision and treatment planning [81]. The expectations of treatment, expecially a surgical treatment involving cranio-facial area, might greatly differ from the patient to the surgeon according to the different experience rate. Indeed, this kind of surgery does not only involve rehabilitation of functions but an important role of aesthetics needs to be considered. Most of the selected patients presented social impairment due to aesthetic consequences of the trauma or pathological situation that caused the bone defect and the expectation from surgery might be over- rated from the patients. For the afore mentioned reasons surveys were prepared to be answered from patients and surgeons participating the study.

First the results were analyzed separately for the two categories of respondents, then they were compared for the same questions. As regard for the patients the level of pain/discomfort and the level of aesthetic perception at different timepoints after surgery were analyzed. Patients revealed to have a significant reduction of the pain/discomfort only 4 weeks after surgery compared with the immediate post-treatment. Apparently, they did not significantly feel the difference between the pain/discomfort at 2 weeks and at 4 weeks after surgery. Moreover, the level of aesthetic perception was evaluated showing that the perception improved only from 1 year after surgery if compared to the immediate post-treatment. Indeed, the aesthetic perception of the improvement of the patient might be related to the presence of edema in the first months after surgery that might not show the real aesthetic result. Fortunately, a good correspondence between the real and the expected aesthetic result was found.

Also, surgeons who performed the surgeries answered a survey which was different for some questions from the patients’ questionnaire and similar for others. Surgeons found easier to perform surgery with custom made graft compared to their experience with traditional bone graft. This result might be related first to the difficulty to perform the surgery by managing the donor site which is not needed with the custom-made graft.

Moreover, the virtual planning might help the surgeon in visualizing the surgery technique and plan the surgery as best as it is possible, then reducing the need for improvisation during the surgery itself.

Regarding the aesthetic improvement perception from the surgeons no differences were

detected from the time immediately after the surgery to 1 year after surgery. This result

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This study was performed with a limited number of patients, a large-scale, multicenter study with a longer follow-up should be encouraged. Another limitation of the present study is that all patients enrolled were adults. In hydroxyapatite bone cement cranioplasty, secondary head asymmetry has been frequently observed in pediatric patients.[82]

Although the number of cases was small with short follow-up period, custom-made implants are highly reasonable options for skull reconstruction. The mean follow- up was 49 months and there were no serious medium-term complications.

The method has many advantages including shorter operating time, decreased technical demand, and the lack of need for a donor graft. Autologous bone is widely used in maxilla-facial reconstruction. It has excellent osteoconductive properties and has been the gold standard [83]. However, it requires meticulous harvesting technique. Donor site morbidity is an issue, and bone grafts cannot be used to fill large defects. In some studies, bone resorption has been reported at rates from 3% to 12% [84-86], which often necessitate secondary interventions to compensate for the loss [87, 88].

Plastic surgeons have searched for an ideal material to use in skull reconstruction. Such material should be easy to manufacture, be durable, strong, lightweight, non- ferromagnetic, and noncarcinogenic. The bio-compatibility of titanium is well established[89]. It is robust enough to resist secondary trauma while providing maximal stability of the cranial vault. Furthermore, titanium implants generally cause less inflammation and conducts well with surrounding mineralized bone [90].

In a previous experience with porous titanium implants (not custom made), we found tissue ingrowth into the implant. With advancement in computer-assisted manufacturing processes, titanium implants could be fabricated using electron beams to print titanium structure in 3D [91].

In our experience, the implants fit the defect precisely without any dead space. The precision of the marginal reproductions has improved the stability of the implant. Defect, the graft can be made precisely.

However, titanium is resistant to bacterial colonization and causes less inflammation.

Though our experience none of the titanium implants became infected during the follow up period. We feel that proper perioperative antibiotic prophylaxis and adequate soft tissue coverage was helpful in minimizing these complications.

The costs of implants range from €2500 to €5050 (mean, €3733) [92]. Despite this,

patients were satisfied with the choice to receive custom titanium implants and did not

complain regarding the cost of implant.

The limitations of this study are small sample size and lack of long-term follow-up data.

Although there are no early complications and patients remain satisfied, long-term follow up is needed for signs of infection and impaired wound healings as reported in previously published cases[92].

Biomechanical stability, cerebral protection, and cosmetic outcome are significant factors to consider when selecting a source material. In these aspects, custom-made 3D titanium implants can be a great option for skull reconstruction.

The 3D design allows the anatomy to be respected, and the operation is significantly simplified with the use of the cutting guides and the pre-drilling. There is also no morbidity of a donor area, which is a considerable advantage for the patient in terms of postoperative comfort in the short and long term.

The mechanical behavior and the mechanical strength of the porous titanium used for these prostheses has been assessed and compared to cortical bone. These titanium prostheses are hollow, but implants can be included on demand.

This option is accessible to all surgeons, without any need to master microsurgical

techniques. There is also no donor area complication for the patient. The results achieved

are encouraging, and at the same time, technological advances will probably allow

implantology solutions to be provided.

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10 C ONCLUSION

According to the results of the present study custom made bone graft made with laser sintering technique represents a valid alternative to traditional bone grafts with high clinical accuracy and the advantage to avoid morbility of the donor site or of the patient due to animal grafting. The level of pain and discomfort for the patients was acceptable and like the surgery with traditional bone graft, moreover the aesthetic improvement perception grew over the first year after surgery. The custom-made bone graft for the cranio-facial region were found easy to place and plan by the surgeons, who noted an aesthetic improvement from the immediate post-treatment interval time and found this aesthetic improvement like the expectations, as for the patients.

11 F UTURE RESEARCH

11.1 I NTRODUCTION

Polyetheretherketone (PEEK) is a polymer that has many potentials uses in dentistry: the aim of this work is to highlight the fields of applications of this material and to foresee other potential future applications.

PEEK is an aromatic, rigid semi-crystalline thermoplastic polymer originally introduced by Victrex PLC in the early 1980s, and in the last three decades has been increasingly employed as a biomaterial for orthopedic and spinal implants [93, 94] whether the most common material for dental implants has been titanium, due to its features of biocompatibility and high resistance to corrosion and strain[95].In dentistry PEEK has been employed, at first, as a material for removable dentures and fixed crown and bridges. Recently, some studies speculated on the possibility to develop hypersensitivity or allergy against titanium and its alloys[96] and argued on effective inertness of metal alloys exposed to oral environment[97]: these are the main reasons that lead to test efficient alternatives to traditional implants; the main branches of study are zirconia implants[97, 98] and PEEK implants[99]. PEEK enhance bone healing and osseointegration, it has an elastic modulus of 3,6GPa, much more similar to bone than titanium’s one, it has bacteriostatic activity and neither allergy nor electrosensibility risk;

moreover, being white it provides better aesthetic qualities, avoiding the presence of the metal grey halo in thin biotypes.

Furthermore, PEEK is feasible for fused filament formation (FFF) with 3D printing systems:

this features allows the deployment with CAD-CAM protocols and the realisation of

custom made items either for prosthetic or orthodontic appliances[100].

The wide variety of its employments relies on its features of bone-like stiffness, good biocompatibility, excellent mechanical properties in load bearing. Moreover, PEEK composites have been reinforced by adding fibres like graphite (PTFE, Carbon, Graphite Filled PEEK), hydroxyapatite (PEEK-HA) as a possible scaffold for bone reconstructive ƉƵƌƉŽƐĞƐ Žƌ ɴ-tricalcium phosphate. A new biocompatible biomaterial : PEEK / ɴ-TCP / TiO

composite this material engineering leads to a huge amount of capacity and yields an adaptivity and a suppleness that make PEEK feasible for almost any kind of use in dental field.

As far as the wide range of application of PEEK in dental is concerned, this material could play a key role in the next few years: improving the bioactivity of PEEK and his mechanical performances will be a major challenge that perhaps could be extremely rewarding.

11.2 L ABORATORY TESTS

In order to verify the citocompatibility of the polymer, laboratory test with blood and with human fibroblast were carried out. The materials verified were a rod of printed ŶĂƚƵƌĂůW<ĂŶĚĂ^ŵĂƌƚƉŝŬΠŝŵƉůĂŶƚƚƌĞĂƚĞĚǁŝƚŚɴ-TCP/TiO

.

11.3 M ATERIALS AND M ETHODS

The first trial was a SEM scan with a drop of blood in order to verify blood cell behaviour in a short-term exposure. Both materials had been sterilized at 134º and blood was collected from the same donor. A single drop was drained off, interface was fixed with Karnofsky liquid and SEM scans were performed.

11.4 R ESULTS

The two PEEK materials showed two very different demeanour yet interfacing the blood:

printed pure PEEK showed its hydrophobic features whether implant PEEK, treated with

ɴ-TCP/TiO

displayed the wettability gained from the engineering. This converse activity

may lead ƚŽĐŽŶĨŽƵŶĚŝŶŐƌĞƐƵůƚƐ͗ŝŶƚŚĞĨŝƌƐƚƐĂŵƉůĞƚŚĞĐŽŶƚĂĐƚĂŶŐůĞȺ

was wide and

the drop of blood was difficult to spread over the surface, whether in the implant, thanks

ƚŽŝƚƐƐƵƉĞƌĨŝĐŝĂůƚƌĞĂƚŵĞŶƚǁŝƚŚɴ-TCP/TiO

, scattered openly and yielded a thin layer with

ĂƚŚŝŶĐŽŶƚĂĐƚĂŶŐůĞȺ

. This occurrence led to oxidation stress of red blood cells (RBC)

before the fixation process was over and outbreak of schistocyte, irregularly shaped,

jagged and with pointed ends (Fig. X).

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Figure 43 erythrocyte biocompatibility test

Nevertheless this sign of RBC distress is not related to the material itself, because PEEK

showed a good biocompatibility in the areas where the layer was thicker, especially at the

bottom of the thread where it merged: there is no sign of cellular lysis and the RBCs are

healthy and organised (Figure 42).

Figure 44 erythrocyte biocompatibility test

In the printed sample, instead, RBCs didn’t suffered from osmotic distress and issued a

good pattern of organisation and the creation of a consistent fibrin network. (Figure 43)

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Figure 45 erythrocyte biocompatibility test.

11.5 C ONCLUSIONS

As far as this preliminary test is considered, PEEK proved to be fully biocompatible

ǁŚĞƚŚĞƌŝŶƉƌŝŶƚĞĚŽƌŐĂŶŝĐĨŽƌŵĂŶĚŝŶƚŚĞɴ-TCP/TiO

treated milled formula. Though,

the fields of deployment could be different: the treated surface performs a better

wettability and then a better clot formation and stabilisation, utterly relevant in peri-

implant bone healing; the printed PEEK instead could be exploited for creation of surgical

guides, also for the easily managing of printing and customising and its hydrophobicity

could also be favourable in manteinance of neatness of the surgical site.

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12 C ASE E XAMPLE

In this chapter we will illustrate the most complex case we have treated. The patient B.A

of 61 years after a dental visit due to a frontal anterior sector of parodontopathy

performed a CT scan that showed the presence of a tumor mass in this site.

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144

After the resective surgery of this lesion the patient presented tumor recurrence

within a few months. For this reason he underwent 2 additional resective surgery

in order to remove the tumor recurrences. At the end presented the complete

removal of the body of the jaw. Previous reconstructive surgery interventions

carried out together with the resective request have failed. The patient was unable

to perform a regular diet and had severe impairment of language and aesthetic-

functional.

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148

150

Therefore, it was decided to reconstruct the mandible with a CAD-cam modeling technique and a medical titanium construction with laser sintering technology. First difficulty of the case is due to the fact that the patient has undergone a series of resective interventions, radiotherapy and the non-functionalization of the remaining structures.

Therefore the mandibular branches are displaced due to the temporal contraction.

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The pre-intervention CT has been superimposed with the post tac in order to have the

original position of the mandible.

154

156

Afterwards the post-operative mandibular branches were superimposed on the pre-

mandible, to have the mandibular branches in the desired position, ie the one before the

reset surgery.

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From this new anatomy it has begun to shape a mandibular body that had the following characteristics:

- reflected the original anatomy

- allowed to suture the structures (therefore with the presence of holes) - had the possibility of fixing with osteosynthesis screws

- was prepared for a future dental prosthesis

- be as small as possible, having lost the anatomical loggia of the jaw

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168

One month after the surgical intervention, the patient was discharged and now presented

an improved functionality and aesthetics.

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13 O THER W ORKS DURING P H D (2014-2017)

13.1 F ASTUCA R, L ORUSSO P, L AGRAVÈRE MO, M ICHELOTTI A, P ORTELLI M, Z ECCA

PA, D'A NTÒ V, M ILITI A, N UCERA R, C APRIOGLIO A. D IGITAL EVALUATION OF NASAL CHANGES INDUCED BY RAPID MAXILLARY EXPANSION WITH DIFFERENT ANCHORAGE AND APPLIANCE DESIGN . BMC O RAL H EALTH . 2017 J UL

14;17(1):113. DOI : 10.1186/ S 12903-017-0404-3. P UB M ED PMID:

28705206; P UB M ED C ENTRAL PMCID: PMC5513127.

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13.2 C APRIOGLIO A, B ERGAMINI C, F RANCHI L, V ERCELLINI N, Z ECCA PA, N UCERA R, F ASTUCA R. P REDICTION OF C LASS II IMPROVEMENT AFTER RAPID MAXILLARY EXPANSION IN EARLY MIXED DENTITION . P ROG O RTHOD . 2017 D EC ;18(1):9. DOI : 10.1186/ S 40510-017-0163-3. E PUB 2017 A PR 3. P UB M ED PMID:

28367605; P UB M ED C ENTRAL PMCID: PMC5376539.

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13.3 C APRIOGLIO A, F ASTUCA R, Z ECCA PA, B ERETTA M, M ANGANO C, P IATTELLI A, M ACCHI A, I EZZI G. C ELLULAR M IDPALATAL S UTURE C HANGES AFTER R APID

M AXILLARY E XPANSION IN G ROWING S UBJECTS : A C ASE R EPORT . I NT J M OL S CI . 2017 M AR 11;18(3). PII : E615. DOI : 10.3390/ IJMS 18030615. P UB M ED

PMID: 28287481; P UB M ED C ENTRAL PMCID: PMC5372631.

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