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Article A Protocol for the Use of a Combined Microvascular Free Flap with Custom-Made 3D-Printed Total Temporomandibular Joint (TMJ) Prosthesis for Mandible Reconstruction in Children

Krzysztof Dowgierd 1,* , Rafal Pokrowiecki 2,*, Maciej Borowiec 2, Marcin Kozakiewicz 3 , Dominika Smyczek 4 and Łukasz Krakowczyk 5

1 Head and Neck Surgery Clinic for Children and Young Adults, Department of Clinical Pediatrics, University of Warmia and Mazury, ul. Oczapowskiego 2, 10-719 Olsztyn, Poland 2 Head and Neck Surgery Department—Maxillofacial Surgery Department, Craniofacial Center, Regional Specialized Children’s Hospital, ul. Zolnierska 18A, 10-561 Olsztyn, Poland; [email protected] 3 Department of Maxillofacial Surgery, Medical University in Lodz, Pl. Hallera 1, 90-647 Łodz, Poland; [email protected] 4 Department of Pediatric Surgery and Urology, John Paul II Upper Silesian Child Health Centre, Independent Public Clinical Hospital no. 6 of the Medical University of Silesia in Katowice, ul. Medykow 16, 40-752 Katowice, Poland; [email protected] 5 Branch in Gliwice, Oncological and Reconstructive Surgery Clinic, Maria Sklodowska-Curie Institute—Oncology Centre (MSCI), ul. Wybrzeze Armii Krajowej 15, 44-100 Gliwice, Poland; [email protected] Citation: Dowgierd, K.; Pokrowiecki, * Correspondence: [email protected] (K.D.); [email protected] (R.P.); R.; Borowiec, M.; Kozakiewicz, M.; Tel.: +48-604-436-411 (K.D.) Smyczek, D.; Krakowczyk, Ł. A Protocol for the Use of a Combined Abstract: Extended postoperative mandibular reconstructions due to orofacial disease involving the Microvascular Free Flap with temporomandibular joint (TMJ) in immature patients remain a challenge as a result of ongoing growth, Custom-Made 3D-Printed Total Temporomandibular Joint (TMJ) which is usually affected by the disease and treatment. Current reconstructive techniques based fully Prosthesis for Mandible on alloplastic total joint replacement fail to meet fully the anatomical and functional requirements for Reconstruction in Children. Appl. Sci. the masticatory system and speech development. Fourteen children aged 12.6 ± 2.6 with tumors or 2021, 11, 2176. https://doi.org/ congenital deformities affecting the mandible and TMJ were included in the study. Radical surgical 10.3390/app11052176 treatment according to our own protocol was performed through microvascular anastomotic flap reconstruction of the soft tissues and bones, together with total TMJ custom replacements. Follow-up Academic Editor: lasted 2–6 years. During the follow-up, increases in the mandible body (13% growth) and ramus Tommaso Lombardi (12% growth) were observed, both of which were related (p < 0.001). This is the first report concerning the immediate reconstruction of the mandible with ramus and total TMJ in children and adolescents Received: 28 December 2020 that combines a free vascularized graft and total individual prosthesis of the TMJ. The presented Accepted: 25 February 2021 technique enabled optimal function of the TMJ, growth of the mandible, and further rehabilitation of Published: 2 March 2021 the patients. The technique was demonstrated to be safe, reliable, and provide good functional and cosmetic outcomes. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- Keywords: maxillofacial; pediatric; surgery; cancer; reconstruction; microsurgery; TMJ; custom im- iations. plants

1. Introduction Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Restoring the anatomical shape and function of the temporomandibular joint (TMJ) This article is an open access article is one of the most demanding and complex treatments in craniofacial surgery due to the distributed under the terms and sophisticated and unique structure and physiology. In adults, TMJ reconstruction is most conditions of the Creative Commons frequently required due to degenerative diseases, accident trauma, or tumors [1]. There Attribution (CC BY) license (https:// are many surgical procedures and techniques for the treatment of a failed TMJ. The most creativecommons.org/licenses/by/ commonly described are: 4.0/).

Appl. Sci. 2021, 11, 2176. https://doi.org/10.3390/app11052176 https://www.mdpi.com/journal/applsci Appl. Sci. 2021, 11, 2176 2 of 14

• Attachment of the resected condyle as a nonvascularized transplant to the end of the bone free flap; • Insertion of a condylar prosthesis in addition to the vascularized bone graft into the glenoid fossa or the use a free bone graft alone, such as a fibula free flap, second metatarsophalangeal joint free flap, vascularized scapular, or clavicle flap; • Use of nonvascularized tissues, such as a costochondral rib flap with a deep circumflex iliac artery flap. At present, the use of alloplastic total joint replacement (TMJR) (with or without bone grafting) is widely accepted and has presented satisfactory long-term outcomes. While TMJR is the scientifically proven treatment of choice in adults, the optimal protocol for TMJ reconstruction in immature patients remains unclear. The resection of part of the mandible with its condyle and the need for reconstruction of its lost elements in children frequently have different pathological backgrounds and desired treatment needs. In children and adolescents, the TMJ loses its physiological function mostly due to malignancies, congenital deformities, and ankyloses [2]. As a consequence this results in the disturbance of orofacial development, asymmetry, malocclusion, breathing, and food intake problems, which require long-term multidisciplinary dental treatment, rehabilitation, physiotherapy, and psychological support since the disease frequently results in social distancing, depression, and mental health problems [3]. Therefore, there is an undisputable need to develop reliable techniques that enable functional reconstruction of the TMJ in children and adolescents while allowing for subsequent physiological growth of the orofacial skeleton, a reduction in postoperational complications and a reduction in the need for future secondary surgeries. The first reports describing the sole use of alloplastic devices in immature patients were published by Keyser et al. [4], Lypka et al. [5], and Cascone et al. [6]. While these described satisfactory results, they indicated the need for further studies in this area. Additionally, data from the clinical studies have implied the justified use of microvascularized bone grafting techniques in the reconstruction of the resected mandible in children [7–9]. Virtual surgical planning (VSP) and custom surgery protocols have found reliable application in contemporary dentistry and oral surgery when plastic, metal, or ceramic materials are used [10,11]. These materials are commonly used in dental implant positioning and peri-implant alveolar surgery (composite, acrylic resins, vacuum-formed thermoplastic matrix) as well as individualized abutment and prosthetic superstructure manufacture (CAD CAM, ceramic). They are also used in the manufacture of individualized maxillofacial osteosynthesis microplates and implants (titanium sinters and solid titanium) and face implants (silicone, high-density polyethylene, e.g., PEEK) [12–14]. The general goal of contemporary 3D planning, custom surgery, and prosthetics is to decrease patient morbidity, provide individualized and precise surgical treatment, reduce downtime, and perform body reconstruction with the highest functionality [14,15]. This study presents the first protocol for postresection reconstruction of the mandible with vascularized bone free flaps stabilized with VSP-planned and 3D custom temporomandibular joint replacement in children. The primary purpose of this manuscript is to introduce and further familiarize dentists and surgeons with the techniques of VSP and microsurgery in children, in order to better plan overall dental and orthopedic treatments.

2. Materials and Methods Ethics approval for this study was received from the Maria Skłodowska-Curie Memo- rial Cancer Center Ethics Committee in Gliwice (KB 430-15/17). Patients and their legal guardians provided informed consent. A total of 14 patients (10 male/4 female) aged 8–17 years old, treated at our institution between 2015 and 2019 due to malignant/benign tumors or congenital deformities affecting the mandible and TMJ, were enrolled in the study. The protocol for TMJ reconstruction assumed the following: preoperative examination and imaging (orthopantomogram, head and neck, abdomen, pelvis, and lower limb CT scans with contrast), virtual imaging (Figure1), stereolithographic models, production of Appl. Sci. 2021, 11, x FOR PEER REVIEW 3 of 14

8–17 years old, treated at our institution between 2015 and 2019 due to malignant/benign tumors or congenital deformities affecting the mandible and TMJ, were enrolled in the Appl. Sci. 2021, 11, 2176 study. The protocol for TMJ reconstruction assumed the following: preoperative3 of 14 examination and imaging (orthopantomogram, head and neck, abdomen, pelvis, and lower limb CT scans with contrast), virtual imaging (Figure 1), stereolithographic models, production of 3D custom-made resection templates (Figures 1b,c and 2), and 3D custom-made resection templates (Figure1b,c and Figure2), and temporomandibular temporomandibular joint implants designed for graft fixation (Figures 1d and 2d) (ChM, joint implants designed for graft ﬁxation (Figures1d and2d) (ChM, Poland, EC Certiﬁcate, Poland, EC Certificate, NO:60099942 0001; ISO 9001:2015, ISO 3485:2016.3). NO:60099942 0001; ISO 9001:2015, ISO 3485:2016.3).

(a) (b)

FigureFigure 1. Virtual 1. Virtual imaging imaging and planning and planning,, with: ( with:a) planning (a) planning of the resection of the resection area; (b) s area;urgical (b ) surgical guideway for resection osteotomies; (c) surgical guideway for graft harvesting osteotomies; and guideway for resection osteotomies; (c) surgical guideway for graft harvesting osteotomies; and (d) microvascularized graft supported with customized temporomandibular joint (TMJ) prosthesis (d) microvascularized graft supported with customized temporomandibular joint (TMJ) prosthesis consisting of polymeric glenoid fossa and titanium, and osteosynthesis trauma plate 2.0 (ChM, Bialystokconsisting, Poland). of polymeric glenoid fossa and titanium, and osteosynthesis trauma plate 2.0 (ChM, Bialystok, Poland). Resection of the mandible ramus within the affected TMJ with/without the body of Resection of the mandible ramus within the affected TMJ with/without the body the mandible was performed through the conventional submandibular approach, and of the mandible was performed through the conventional submandibular approach, and exposure of the TMJ was performed through the conventional preauricular approach. exposure of the TMJ was performed through the conventional preauricular approach. Facial nerve branches were identified and preserved using intraoperative Facial nerve branches were identified and preserved using intraoperative neuromonitoring. neuromonitoring. Prior to resection osteotomy, customized surgical templates were applied Prior to resection osteotomy, customized surgical templates were applied in order to ensure in order to ensure a precise cut and adjust the osteotomy line to the graft (Figure 2a). The a precise cut and adjust the osteotomy line to the graft (Figure2a). The microvascularized microvascularized bone graft was harvested either from the fibula (fibula free flap (FFF)) bone graft was harvested either from the fibula (fibula free flap (FFF)) or iliac crest (iliac or iliac crest (iliac crest free flap (ICFF)) with use of customized resection templates to crest free flap (ICFF)) with use of customized resection templates to obtain the desired obtain the desired amount and shape of the graft (Figure 2b,c). After resection, the amount and shape of the graft (Figure2b,c). After resection, the microvascularized graft microwasvascularized conventionally graft connected was conventionally to the facial and/or connected temporal to the vesselsfacial inand/or order temporal to provide vesselssufficient in order blood to supply,provide connected sufficient toblood the 3Dsupply, customized connected TMJ to prosthesis the 3D customized and stabilized TMJ by prosthesisthe titanium and stabilized reconstruction by the plate titanium 2.0 (ChM, reconstruction Bialystok, plate Poland) 2.0 (ChM, (Figure Bialystok,2d). Poland) (Figure 2d). Appl. Sci. 2021, 11, 2176 4 of 14 Appl. Sci. 2021, 11, x FOR PEER REVIEW 4 of 14

(a) (b)

FigureFigure 2. Intraoperative 2. Intraoperative photographs photographs showing showing examples examples of: ( ofa): medial(a) medial mandible mandible resection resection template; template (b;) iliac(b) iliac graft graft harvesting harvesting template; (c) fibular graft harvesting template; and (d) intraoperative view of the graft (blue arrow) connected template; (c) fibular graft harvesting template; and (d) intraoperative view of the graft (blue arrow) connected to the to the customized prosthesis and reconstruction plate (green) before fixing. customized prosthesis and reconstruction plate (green) before fixing. After the surgery, a control orthopantomogram and CT scan were performed in order to confirmAfter the the surgery, proper position a controling orthopantomogram of the graft and prosthesis. and CT D scanuring were the post performedoperative in order toperiod confirm the theviability proper of the positioning osteocutaneous of the free graft flaps and was prosthesis. assessed via During clinical themonitoring postoperative period(Doppler the imaging viability and of thephysical osteocutaneous examination) free: the flapsflap was was inspected assessed every via clinical hour on monitoring the (Dopplerfirst day imagingand every and 3–5 physical h for the examination): next 4 days. Mean the flappost wasoperati inspectedve downtime every was hour 10 on–14 the first daydays. and All every patients 3–5 were h for referred the next to 4physiotherapy days. Mean postoperativeshortly after the downtime surgery. During was 10–14 the days. Allpreoperative patients were and follow referred-up periods, to physiotherapy maximal interincisal shortlyafter opening the (MIO), surgery. lateral During deflation the preop- erativeon the andreconstructed follow-up side, periods, asymmetry maximal, and growth interincisal of the operated opening and (MIO), contralateral lateral deflationsides on thewere reconstructed measured (orthopantomogram, side, asymmetry, cephalometric and growth X of-ray the superimposition, operated and CT contralateral scans). The sides werepatients measured were functionally (orthopantomogram, assessed by cephalometricexamining masticatory X-ray superimposition, function, speech, and CT scans). aesthetic appearance. Microplates were removed 3–6 months after the surgery in order to The patients were functionally assessed by examining masticatory function, speech, and allow further sufficient growth of the mandible. Statgraphics Centurion XVI, StarPoint aesthetic appearance. Microplates were removed 3–6 months after the surgery in order Technologies INC., Virginia, USA, was used for statistical analyses. Linear regression toanalysis allow further and one sufficient-way analysis growth of variance of the mandible. were used Statgraphics to evaluate the Centurion clinical material. XVI, StarPoint TechnologiesStatistical significance INC., The was Plains, established VA, USA, at p was< 0.05. used for statistical analyses. Linear regression analysis and one-way analysis of variance were used to evaluate the clinical material. Statistical3. Results significance was established at p < 0.05. A total of 14 patients aged 8–17 years old (10 male, 4 female) were enrolled in the 3.study. Results All patients underwent mandibulectomy (ramus and body n = 12; ramus only n = 2) withA total immediate of 14 patients3D-assisted aged TMJR 8–17 supported years old by microvascular (10 male, 4 female) free flap werereconstruction enrolled in the study.(FFF or All ICFF) patients (Table underwent 1). mandibulectomy (ramus and body n = 12; ramus only n = 2) with immediate 3D-assisted TMJR supported by microvascular free flap reconstruction (FFF or ICFF) (Table1). Appl. Sci. 2021, 11, 2176 5 of 14

Table 1. Summary of patients enrolled in the study, including: diagnosis, level of malignancy, resection extent, and reconstruction type. Additional surgery performed after the follow-up (2–6 years postoperative): none—orthodontic treatment and implant placement were performed with use of a primary graft after the follow-up; reconstructive—orthodontic treatment and implant placement required secondary bone grafting; orthognathic—additional orthognathic surgery was required in order to treat skeletal deformation at the time of the TMJR surgery or after the follow-up.

Mandibulectomy TMJ Reconstruction Follow-Up Additional Gender Age [Year] Diagnosis Malignancy Final Treatment Range Replacement Type [Years] Surgery Male 8 Fibroma Ossiﬁcans Benign Ramus only Unilateral ICFF 5 None Ortodontic Male 8 Fibrous Displasia Benign Ramus only Unilateral ICFF 5 None Ortodontic Female 10 Sarcoma Cancer Ramus & Body Unilateral FFF 4 None Ortodontic & Dental Implants Male 11 Sarcoma Cancer Ramus & Body Unilateral FFF 6 None Ortodontic Female 12 Severe Deformation Benign Ramus & Body Bilateral FFF 4 Ortognathic Ortodontic Male 13 Fibrous Displasia Benign Ramus & Body Bilateral FFF 2 None Ortodontic Male 13 Severe Deformation Benign Ramus & Body Unilateral FFF 5 Ortognathic Ortodontic & Dental Implants Male 13 Sarcoma Cancer Ramus & Body Unilateral FFF 5 None Ortodontic Male 13 Sarcoma Cancer Ramus & Body Unilateral ICFF 5 Reconstructive Ortodontic & Dental Implants Male 14 Amelobastoma Benign Ramus & Body Unilateral FFF 4 None Ortodontic & Dental Implants Male 15 Fibrous Displasia Benign Ramus & Body Unilateral FFF 2 None Ortodontic Female 15 Amelobastoma Benign Ramus & Body Unilateral FFF 5 Reconstructive Ortodontic & Dental Implants Female 17 Amelobastoma Benign Ramus & Body Unilateral ICFF 5 Ortognathic Ortodontic & Dental Implants Central Cell Giant Male 14 Benign Ramus & Body Unilateral FFF 4 None Ortodontic & Dental Implants Granuloma Appl. Sci. 2021, 11, x FOR PEER REVIEW 1 of 14

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Ten patients were operated on due to benign diseases: ameloblastoma (n = 3), fibrous dysplasiaTen patients (n = 3), were central operated giant on cell due tumorto benign (n diseases:= 1), and ameloblastoma fibroma ossificans (n = 3), (n fi- = 1). brousMandibulectomy dysplasia (n with = 3), centralTMJ was giant performed cell tumor due (n to = 1),sarcoma and fibroma in four ossificans patients (nand = 1).due to Mandibulectomy with TMJ was performed due to sarcoma in four patients and due to congenital deformations in two patients: one due to congenital deformations (hemifacial congenital deformations in two patients: one due to congenital deformations (hemifacial macrosomia) and one for acquired ankylosis of the TMJ. The vast majority of cases were macrosomia) and one for acquired ankylosis of the TMJ. The vast majority of cases were treatedtreated with with an an FFF FFF graft graft (n = (n 11) = ( p 11)< 0.005). (p < Unilateral0.005). Unilateral defects requiring defects requiring surgical inter- surgical ventionintervention were the were most the common most co (pmmon< 0.005). (p Only< 0.005). two patients Only two required patients bilateral required surgery bilateral (alsosurgery performed (also performed immediately): immediately): one due to one fibrous due dysplasiato fibrous and dysplasia the other and due the to other severe due to deformation.severe deformation. In the group In the of group patients of patients operated operated on unilaterally, on unilaterally, mandible mandible growth was growth evaluated.was evaluated. The distance The distanc betweene between reference reference points on thepoints day on of surgerythe day and of atsurgery the endpoint and at the ofendpoint the study of was the measured study was in eachmeasured patient. in In each order patient. to evaluate In order the growth to evaluate of the mandiblethe growth of ramusthe mandible and body, ramus auricular and (Ar)–gonion body, auricular (Go) and (Ar) gonion–gonion (Go)–pogonion (Go) and gonion (Po) were (Go) used–pogonion as reference(Po) were points, used respectively,as reference onpoints, the operated respectively side and, on thethe opposite, operated healthy side and control the opposite, side. Additionally,healthy control the si SNBde. anglesAdditionally, were measured the SNB after angle thes were surgery measured and during after the the follow-up surgery and (Seeduring Figure the3 ).follow-up (See Figure 3).

FigureFigure 3. 3. RepresentativeRepresentative laterallateral photographphotograph of of 3D3D imagingimagingof of thethe referencereference pointspointsused used forfor thethe measurements described in the Table 2. The auricular (Ar)–gonion (Go) sections were used to measurements described in the Table2. The auricular (Ar)–gonion (Go) sections were used to measure changes in height of the mandible ramus; the gonion (Go)–pogonion (Po) sections were measure changes in height of the mandible ramus; the gonion (Go)–pogonion (Po) sections were used to measure changes in the length of the mandible body. The SNB angle was used to measure used to measure changes in the length of the mandible body. The SNB angle was used to measure the anterior growth of the mandible. the anterior growth of the mandible.

TheThe measurements measurements enabled enabled straightforward straightforward evaluation evaluation of the overall of the mandible overall growth mandible aftergrowth the surgeryafter the and surgery allowed and the allowed growth ofthe the growth grafted of side the to grafted be compared side to with be thecompar healthyed with sidethe healthy in each patientside in (Tableeach 2patient). (Table 2).

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Table 2. Measurements of mandible growth on the day of surgery and during the follow-up (2–6 years postoperative), where MIOpre is maximal interincisal opening before resection and reconstruction; MIOpost is maximal interincisal at the ﬁnal follow-up; Ramus OP is the height of the operated ramus before surgery; Ramus OP’ is the height of the operated ramus after surgery; Body OP is the length of the operated body before surgery; Body OP’ is the length of the operated body after surgery; Ramus C is the height of the nonoperated ramus before surgery; Ramus C’ is the height of the nonoperated ramus after surgery; Body C is the length of the nonoperated body before surgery; and Body C’ is the length of the nonoperated body after surgery. Bilateral N/A: as the procedure was done bilaterally in two patients there was no reference point for estimating the operated vs. nonoperated side for statistical purposes.

Ramus Ramus Body Body Ramus Ramus Body Body Age Mandibulectomy TMJ Reconstruction MIOpre MIOpost SNBpre SNBpost Assymetry Gender OP OP’ OP OP’ C C’ C C’ [Years] Range Replacement Type [mm] [mm] [deg.] [deg.] [mm] [mm] [mm] [mm] [mm] [mm] [mm] [mm] [mm] Male 8 Ramus only Unilateral f_Iliac_F 5 30 69.2 72.5 19.3 20.7 47.3 50 52 54 47.2 51 6 Male 8 Ramus only Unilateral f_Iliac_F 10 35 77 74 28.7 28.7 68.4 68.4 49 51 56 57 0 Female 10 Ramus & Body Unilateral f_Fibula_F 0.5 30 77.2 74.7 41 43.3 89 91 58 65 68 70 0 Male 11 Ramus & Body Unilateral f_Fibula_F 5 35 78.5 79 43 43.5 63.8 64 50 53 53 56 0 Female 12 Ramus & Body Bilateral f_Fibula_F 25 35 56 82.6 n/a n/a n/a n/a n/a n/a n/a n/a 0 Male 13 Ramus & Body Bilateral f_Fibula_F 5 35 74 80 n/a n/a n/a n/a n/a n/a n/a n/a 3 Male 13 Ramus & Body Unilateral f_Fibula_F 0.5 35 69.1 75.5 45.8 51.8 50.5 58.6 52.7 53 54.8 61 5 Male 13 Ramus & Body Unilateral f_Fibula_F 15 35 77.2 75.4 29.9 31 35.4 37.5 56 57.5 70 77.4 5 Male 13 Ramus & Body Unilateral f_Iliac_F 40 40 65 73.1 34 42.2 41 42.9 51 56 67 70 0 Male 14 Ramus & Body Unilateral f_Fibula_F 10 40 64 76 37 39 98 99 47.7 56 62.1 72 4 Male 15 Ramus & Body Unilateral f_Fibula_F 10 35 72 74.4 41.6 43 27.5 27.5 45 56 49 72 6 Female 15 Ramus & Body Unilateral f_Fibula_F 10 45 69.4 71 32.3 37.2 56.3 61.5 53 61 64 73 7 Female 17 Ramus & Body Unilateral f_Iliac_F 35 45 68 74 30.3 30.5 30 29 48 58 49 61 0 Male 14 Ramus & Body Unilateral f_Fibula_F 10 40 71 74 35 38.6 31.1 47.2 55 59 60 67 4 Appl.Appl. Sci. Sci. 2021 20, 2111,, 11x FOR, x FOR PEER PEER REVIEW REVIEW 1 of1 of14 14

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In Inthe the follow follow-up,-up, there there were were no no statistical statistical difference differences observeds observed in inheight height (p (=p 0 =.39 0.)39 or) or InIn the the follow-up, follow-up, there there were were no no statistical statistical differences difference observeds observed in height in height (p = 0.39)(p = 0 or.39) or in inlength length (p (=p 0=. 140.)14 (Figure) (Figure 4) 4)between between the the graft graft and and the the control. control. Therefore, Therefore, the the operated operated inin length length ( p(p= = 0.14) 0.14 (Figure) (Figure4) between4) between the the graft graft and and the control.the control. Therefore, Therefore, the operated the operated sidsied exhibitede exhibited similar similar growth growth of ofthe the ramus ramus and and body body in incomparison comparison to tothe the control control at atthe the sideside exhibited exhibited similar similar growth growth of of the the ramus ramus and and body body in comparison in comparison to the to controlthe control at the at the endpoint of the study. endpointendpoint of of the the study. study.

Box-and-Whisker Plot Box-and-Whisker Plot Box-and-WhiskerBox-and-Whisker Plot Plot Box-and-Whisker Plot Box-and-Whisker Plot

RamusGrowthC[%]RamusGrowthC[%] BodyGrowthC[%]BodyGrowthC[%] RamusGrowthC[%] BodyGrowthC[%]

RamusGrowthOP[%]RamusGrowthOP[%] BodyGrowthOP[%]BodyGrowthOP[%] RamusGrowthOP[%] BodyGrowthOP[%]

96 106 116 126 136 146 156 100 100 105 105 110 110 115 115 120 120 125 125 96 106 116 126 136 146 156 100 105 110 115 120 125 96 106 116 126 136 146 156

(a)( a) (b)( b) FigureFigureFigure 4. Student 4.4. Student’sStudent’s t’s-ttest -testt-test evaluating evaluating evaluating statistical statistical statistical differencesdifferences differences in in the inthe mean the mean mean growth growth growth of the of ramusofthe the ramus (ramusa) and (a ) body(anda) and (bodyb )body of the(b )( graftbof) ofthe andthe graft graft andandhealthy healthy healthy control. control. control. Statistical Statistical Statistical signiﬁcance significance significance was was established was established established at p

TheTheThe difference difference difference between between between the the mean mean valuesvalues values ofof the ofthe the SNB SNB SNB angles angles angles before before before and and afterand after after surgery surgery surgery was signiﬁcant (p = 0.000), which conﬁrms that physiological anterioinferior growth of the waswas significant significant (p (=p 0 =.000) 0.000), which, which confirms confirms that that physiological physiological anterioinferior anterioinferior grow growth thof ofthe the mandible occurred after the surgery in all patients (Figure5). mandiblemandible occurred occurred after after the the surgery surgery in inall all patients patients (Figure (Figure 5). 5).

Box-and-WhiskerBox-and-Whisker Plot Plot Box-and-Whisker Plot

SNBpostSNBpost [deg.] [deg.] SNBpost [deg.]

SNBpreSNBpre [deg.] [deg.] SNBpre [deg.]

56 56 61 61 66 66 71 71 76 76 81 81 86 86 56 61 66 71 76 81 86

FigureFigureFigure 5. 5. Student5.Student’s Student’s t’s-t-testtest t-test evaluating evaluating evaluating statisticalstatistical statistical differences differences differences in in the thein mean the mean mean value value value of theof theof SNB the SNB angle SNB angle beforeangle before and after surgery. Statistical significance was established at p < 0.005. andbefore after and surgery. after surgery. Statistical Statistical signiﬁcance significance was established was established at p < 0.005. at p < 0.005.

TheTheThe post postoperative postoperativeoperative improvement improvement improvement in inthe the the range range range of of mouth of mouth mouth opening opening opening was was was statistically statistically statistically significantsigniﬁcantsignificant (p (p (=p= 0 = 0.001).001) 0.001) (Figure (Figure (Figure 66)). .6) .

Box-and-WhiskerBox-and-Whisker Plot Plot Box-and-Whisker Plot

MIOpostMIOpost [mm] [mm] MIOpost [mm]

MIOpreMIOpre [mm] [mm] MIOpre [mm]

0 0 10 10 20 20 30 30 40 40 50 50 0 10 20 30 40 50

Figure 6. Student’s t-test evaluating statistical differences in MIO (maximal interincisal opening) FigureFigure 6. 6.Student’s Student’st -testt-test evaluating evaluating statistical statistical differences differences in in MIO MIO (maximal (maximal interincisal interincisal opening) opening) beforebefore and and after after the the surgery. surgery. Statistical Statistical significance significance was was established established at pat < p 0 <.005. 0.005. beforebefore and and after after the the surgery. surgery. Statistical Statistical signiﬁcance significance was was established established at p < at 0.005. p < 0.005.

TheThe average average post postoperativeoperative MIO MIO was was 38 .3875. 75mm mm (mean (mean improvement improvement of of+13. +13.75 75mm) mm), , whichwhich confirms confirms the the beneficial beneficial effect effect of ofthe the surgery surgery on on mouth mouth opening opening (Figure (Figure 7). 7). Appl. Sci. 2021, 11, 2176 9 of 14 Appl. Sci. 2021, 11, x FOR PEER REVIEW 2 of 14

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The average postoperative MIO was 38.75 mm (mean improvement of +13.75 mm), which conﬁrms the beneﬁcial effect of the surgery on mouth opening (Figure7).

(a) (b) (a) (b) Figure 7. Photographs of an 8-year-old patient (a) before and (b) one year after the surgery, showing significant improvementFigure 7. Photographs in theFigure range of 7. ofPhotographsan mouth8-year -openingold of patient an8-year-old and ( asatisfactory) before patient and a (aesthetic )( beforeb) one results. and year (b ) after one year the aftersurgery the, surgery,showing showing significant improvement in thesigniﬁcant range of improvementmouth opening in and the rangesatisfactory of mouth aesthetic opening results. and satisfactory aesthetic results. During the follow-up, genial asymmetry of 3–6 mm was diagnosed in 8 patients During(Table theDuring follow-up,2). Thethe followpatterns genial-up, asymmetryof genial the ramus asymmetry of 3–6 and mm of body 3 was–6 growth mm diagnosed was were diagnos in analyzed 8 patientsed in 8 using patients simple (Table2) .(Tableregression The patterns 2). The testing of patterns the of ramus the of subgroups and the body ramus growth (operated and body were vs analyzedgrowth. control) were using (Figure analyzed simple 8). regres- using simple sion testingregression of the subgroups testing of the (operated subgroups vs. control) (operated (Figure vs. control)8). (Figure 8).

Plot of Fitted Model Plot of Fitted Model RamusGrowthC[%] = sqrt(-13040,6 + 2378,51*sqrt(BodyGrowthC[%])) RamusGrowthOP[%] Plot= 1/(0,00700204 of Fitted Model + 0,248583/BodyGrowthOP[%]) Plot of Fitted Model RamusGrowthOP[%] = 1/(0,00700204 + 0,248583/BodyGrowthOP[%]) RamusGrowthC[%] = sqrt(-13040,6 + 2378,51*sqrt(BodyGrowthC[%])) 125 125 125 125 120 120 120 120

115 115 115 115

110 110

RamusGrowthC[%]

RamusGrowthOP[%] RamusGrowthC[%]

RamusGrowthOP[%] 105 105 105 105

100 100 100 100 96 106 116 126 136 146 156 100 110 120 130 140 150 96 106 116 126 136 146 156 100 110 120 130 140 150 BodyGrowthOP[%] BodyGrowthC[%] BodyGrowthOP[%] BodyGrowthC[%]

(a()a ) (b) (b)

FigureFigure 8. Simple regressionFigureregression 8. Simple tests tests evaluating regressionevaluating pattern tests pattern evaluatings ofs ofmandible mandible patterns growth ofgrowth mandible, (a), (Operateda) growth,Operated site, (a) site, Operated(b) Control(b) Control site, site (b.) Itsite Con- can. It be can be observedobserved that thethe operatedtroloperated site. Itsi si canddee exhibited beexhibited observed decreased decreased that the capacity operated capacity for side for growth exhibitedgrowth over over decreasedtime time when when capacity compared compared for with growth with the over healthy the time healthy side. side. StatisticalStatistical significancewhen was was compared established established with at theat p p< healthy 0.005< 0.005. side.. Statistical signiﬁcance was established at p < 0.005.

During theDuringDuring follow-up the the follow follow period-up-upit period was period observed it wasit was observed that, observed in somethat that, in cases, ,some in some the cases grafted cases, the, side graftedthe grafted side side exhibitedexhibitedexhibited decreased decreased decreased potential potential for potential growth for for in growth comparison growth in comparisonin comparison to the nonoperated to the to nonthe operatednon side,operated but si therede, si bdute, there but there was no statisticallywaswas no no statistically statistically significant significant significant difference difference (differencep > 0.005). (p >There( p0 .>0 05).0. were005). There noThere were free were flap no free failures no freeflap inflapfailures the failures in the in the postoperativepostpostoperativeoperative period or period duringperiod or theor during during 4–5-year the the 4 follow-up.– 54-–year5-year follow Allfollow patients-up.- up.All All exhibitedpatients patients exhibited satisfactory exhibited satisfactory satisfactory functionfunctionfunction of the TMJ, of of the exceptthe TMJ, TMJ, for except except one patient,for for one one who patient patient had, who posterior, who had had posterior dislocation posterior dislocation of dislocation the TMJ of the of TMJthe TMJ prosthesis,prosthesis which was, which treated was bytreated additional by additional rehabilitation. rehabilitation. Contralateral Contralateral excursion excursion was was prosthesis, which was treated by additional rehabilitation. Contralateral excursion was observedobserved in five patients in five afterpatients reconstruction. after reconstruc Theretion. were There no inflammatorywere no inflammatory complications complications observed in five patients after reconstruction. There were no inflammatory complications or biomechanicalor biomechanical problems problems with the with prosthesis the prosthesis itself, such itself as, dislocations such as dislocations or inappropriate or inappropriate or biomechanical problems with the prosthesis itself, such as dislocations or inappropriate positioningposition of theing mandible. of the mandible. Furthermore, Furthermore there were, there no were incidents no incidents of the prosthesis of the prosthesis loosening.loosening.position All patientsing All of patients had the orthodontic mandible. had ortho andFurthermoredontic dental and implant dental, there implant treatment were treatment no performed incidents performed as of the the as prosthesis the final stagefinalloosening. of stage oral rehabilitation ofAll oral patients rehabilitation (Figurehad ortho9 ).(Figuredontic In three 9) and. patients, In dentalthree additionalpatientsimplant, additionaltreatment orthognathic performed orthognath icas the surgerysurgery hadfinal to stage be had undertaken. ofto be oral undertaken. rehabilitation In another In another three (Figure patients, three 9). Inpatients, additional three patientsadditional bone, grafting additional bone grafting was orthognat was hic necessarynecessarysurgery due to the haddue placement to thebe placementundertaken. of the dental of theIn implants. anotherdental implants three patients, additional bone grafting was necessary due to the placement of the dental implants Appl. Sci. 2021, 11, 2176 10 of 14 Appl. Sci. 2021, 11, x FOR PEER REVIEW 3 of 14

FigureFigure 9. 9.3D 3D CTCT reconstructionsreconstructions of of representative representative patients. patientsPatient. Patient 1 1:: (a) (a) tumor tumor of of the the right right mandible mandible bodybody and and ramus, ramus, (b) (b) defect defect after after nonradical nonradical resection resection in another in another department department and andsecondary secondary de- deformation, (c) 3D virtual surgical planning (VSP) reconstruction of the mandible and custom TMJ, formation, (c) 3D virtual surgical planning (VSP) reconstruction of the mandible and custom TMJ, (d) 6 months postoperative, and (e) 24 months postoperative. Patient 2: (a) tumor of the left (d) 6 months postoperative, and (e) 24 months postoperative. Patient 2: (a) tumor of the left mandible mandible body and ramus, (b) defect after nonradical resection in another department and bodysecondary and ramus, deformation, (b) defect (c) afterreconstruction nonradical of resection the mandible in another with departmentfibula without and 3D secondary VSP in another deformation,facility— (c)lack reconstruction of functionality, of the (d) mandible reconstruction with fibulaof the withoutTMJ with 3D stock VSP TMJ in another prosthesis facility—lack and maxillary of functionality,advancement (d) in reconstructionorder to improve of thefunction TMJ with and stockocclusion TMJ— prosthesisfailure due and to maxillary resorption advancement of the previous in orderbone tografting, improve and function (e) 3D VSP and reconstruction occlusion—failure of the due mandible to resorption body, ramus of the and previous custom bone TMJ. grafting, Patient and3: (a) (e) tumor 3D VSP of reconstructionthe left mandible of the body mandible and ramus, body, (b) ramus 3D VSP and customreconstruction TMJ. Patient of the 3 :mandible (a) tumor and of thecustom left mandible TMJ, and body (c) 4 andyears ramus, postop (b)erative 3D VSP. reconstruction of the mandible and custom TMJ, and (c) 4 years postoperative. 4. Discussion 4. DiscussionThe reconstruction of mandibular defects in children is technically and aesthetically challengingThe reconstruction. Additional of mandibular TMJ reconstruction defects in children protocols is technically that provide and aesthetically long-term challenging.functionality Additional in this group TMJ of reconstruction patients are still protocols not full thaty developed provide long-term. In most cases functionality of adult inpatients, this group simple of patients total are joint still replacement not fully developed. (TMJR) In is most usually cases satisfactory of adult patients, because simple the totalrequirements joint replacement related (TMJR)to a growing is usually child satisfactory do not need because to be the met requirements. For children related the main to a growingissues are child associated do not needwith tothe be development met. For children of speec the mainh, the issues masticatory are associated system with, and thethe developmententire craniofacial of speech, region the, which masticatory are dramatically system, and hampered the entire craniofacialwhen the TMJ region, is lost. which The arebest dramatically treatment hampered should restore when the functionality, TMJ is lost. The including best treatment adequate should mouth restore opening, functionality,improving including the airway adequate patency mouth, prevent opening,ing the improving recurrence the of airway the disease patency,, and preventing providing thesatisfactory recurrence aesthetic of the disease,results [2 and,4]. T providingo date, there satisfactory is no proven aesthetic track for results mandible [2,4]. Toand date, TMJ theregrafting is no techniques proven track that for can mandible assist in andthe TMJpostoperati graftingve techniques growth of thatthe jaws can assist of pediatric in the postoperativepatients. Resnik growth claimed of thethat jaws the pediatric of pediatric TMJ patients. may be Resnikreconstructed claimed either that by the distraction pediatric TMJosteogenesis, may be reconstructed autologous reconstruction either by distraction (costochondral osteogenesis, graft, autologous free fibula reconstruction flap), or total (costochondralalloplastic joint graft, replacement free fibula [2] flap),. However, or total alloplastic the growth joint potential replacement of the [ 2 mandible]. However, in thepediatric growth patients potential depends of the mandible on the preservation in pediatric of patients the mandibular depends on epiphyseal the preservation growth of the mandibular epiphyseal growth plates, which are located in the proximal zone of plates, which are located in the proximal zone of the conical subcondylar ridge [16]. the conical subcondylar ridge [16]. Because of this, in immature patients it is advised Because of this, in immature patients it is advised that the condyle be preserved at all costs that the condyle be preserved at all costs when a mandibulectomy is necessary. Condylar when a mandibulectomy is necessary. Condylar preservation has been shown to preservation has been shown to positively influence the growth potential of the mandible positively influence the growth potential of the mandible in the postoperative period [17]. in the postoperative period [17]. The protocol for the reconstruction of a child’s mandible The protocol for the reconstruction of a child’s mandible is more complicated when a is more complicated when a condyle must be removed due to malignancy, is deformed, or condyle must be removed due to malignancy, is deformed, or is absent due to is absent due to deformation, as was the case in the described population of the patients deformation, as was the case in the described population of the patients operated on operated on within this study. within this study. Appl. Sci. 2021, 11, 2176 11 of 14

In the literature, costochondral grafts have been reported as the gold standard for mandible and TMJ reconstruction in children, but nonvascularized autological bone grafts have a tendency to induce osteogenesis [18]. This is the reason that they are not the treatment of choice for the ankylosis of the joints [19]. Costochondral graft fractures, hy- pertrophy of the bone grafts, their unpredictable growth with separation of bone from the chondral part, and resorption in the donor site have been described [20]. Resection of the lower face region without simultaneous reconstruction leads to constrictions of the native soft tissues and dislocations of other bones and, eventually, extreme malocclusion and deformation of the face. These often lead to the need for secondary reconstructions, which are always more difficult and sometimes impossible to conduct. Resection with simultaneous reconstruction of the mandible allows orthodontic treatment and dental rehabilitation for the early restoration of teeth while preventing malocclusion. Indeed, simultaneous microvascular mandibular grafting techniques with satisfactory results have been described by other authors but, again, surgery did not involve the TMJ or enable its sufficient reconstruction when necessary [18,21,22]. Virtual surgical planning and custom biomaterials have already found clinically proven applications in the treatment of orbital trauma [11], cosmetic facial surgery [23], orthognathic surgery [24], free flap reconstruction of midface defects [25], and treatment of facial gunshot wounds and other injuries [26], providing improved efficiency and precision for complex surgical operations and assisting in the restoration of maxillofacial unit functionality, facial volume, symmetry, and har- mony [26,27]. However, no data have been reported to date regarding the reconstruction of the pediatric mandible, its implication in further growth, and the possibilities for dental and orofacial treatment. In this study, we describe the first protocol where VSP and alloplastic prosthesis of the TMJ with microvascular free flaps is combined with 3D planning of the resection areas and shape of the graft, and the precision operation was performed using individually designed surgical guides, which are more commonly used in the reconstructive facial surgery of adults [21,25]. This approach minimizes the risk of unwanted trauma and over-resection, reduces the duration of the surgery, and ensures a perfect fit of the graft at the donor site. The alloplastic 3D custom TMJ prosthesis allows full reconstruction of the lost joint and ensured physiological functioning. Similarly to the previously published results, VSP provides improved reconstruction, precision bony segment contact, and anatomical correction of the bone deficiency [25]. No resorption of the bone grafts was observed in the follow-up. The microvascular graft, fixed to the TMJ prosthesis and mandible by a customized microplate, allows further mandible growth and prevents TMJ ankylosis. In the follow-up, growth of the operated side was observed in comparison to the contralateral healthy side. It must be noted that in pediatric patients, reconstruction plates must be removed within 3–4 months of the reconstruction surgery to allow the continued proper and undisturbed growth of the facial skeleton. The surgical procedure described within this study provides significant improvement in TMJ functionality, mouth opening range, food intake effectiveness and satisfactory aesthetic results. It is worth mentioning that in some cases the planning of the surgery and bone reconstruction should include hypercorrection of the grafted side in order to reduce or eliminate genial asymmetry at the follow up. Three-dimensional VSP has inherent issues that have to be taken into account during the planning stage. Pitfalls resulting from excessive tumor growth, nonfitting of the guides, or misconceived osteotomy lines may lead to incomplete adherence or complete abandonment of VSP-based treatment. Furthermore, it must be noted that communication with the manufacturing engineer is critical for the successful application of 3D-designed biomaterials [28]. Frequently, a multidisciplinary 3D-VSP meeting with a maxillofacial surgeon, orthodontist, oncologic surgeon, and clinical engineer or technician is arranged in order to develop a coherent and prospective surgery and treatment plan [29]. In some cases the design and size of either the surgical guide or the implant itself requires modified and extended operational access in order to properly fit the device. This represents the Appl. Sci. 2021, 11, 2176 12 of 14

most disturbing intraoperative factor as 3D-printed biomaterials usually cannot be easily modified, bent, cut, or trimmed, unlike stock solid titanium implants. VSP requires a highly skilled and experienced surgeon and suitable preoperative planning to take full advantage of VSP’s possibilities. The use of 3D custom implants may increase the overall cost of a single hospitalization, but the benefits of limited downtime and fewer subsequent operations balance the costs of this treatment approach [30,31]. By applying this novel concept to TMJ surgery in immature patients, one may reduce the number of operations, such as distraction osteogenesis or secondary bone grafts, which are frequently performed in cases treated with free grafts only or stock biomaterials. Early reconstruction of the defects may support more physiological mandible growth which, in turn, favors logopedic, orthodontic, dental, and pediatric prosthodontics. With special design of the flap and reconstruction it is possible to reconstruct not only the facial bones but also the soft tissues that are crucial for facial aesthetics. Moreover, more physiological growth of the TMJ and mandible ramus after surgery is beneficial for the reduction in the magnitude of secondary reconstructive and orthognathic surgery as the final treatment for the restoration of occlusion and facial balance.

5. Conclusions This is the ﬁrst report on the immediate reconstruction of the mandible with the ramus and total TMJ in children and adolescents that combines a free vascularized graft and total individual prosthesis of the TMJ. The presented technique allows the optimal function of the TMJ, growth of the mandible, and further rehabilitation of the patients. It is safe, reliable, and provides good functional and cosmetic outcomes. VSP may present some limitations, such as the increased cost of surgery and extensive, multidisciplinary planning and preparation prior to the surgery. However, a properly designed and performed treatment reduces downtime, morbidity, the surgery time, and the number of subsequent operations. Custom guides and implants may not ﬁt correctly when the osteotomy lines are poorly designed or extensive tumor growth is diagnosed. Therefore, it is crucial to implement reliable, quick, and precise planning to enable rapid intervention, from the primary diagnosis to the surgery itself. There is an undisputable need for further studies to establish a gold standard for TMJ reconstruction in immature patients, which is of great importance in pediatric dentistry and orthodontics. Furthermore, the evaluation of this approach on the active growth of a larger group of patients and a longer follow-up period are required in future studies.

Author Contributions: K.D.: conceptualization, methodology, writing—original draft preparation, project administration, funding acquisition, resources; R.P.; writing—original draft preparation, writing—review and editing, visualization, investigation, data curation; M.B.: investigation, software, methodology; M.K.: data curation, formal analysis; D.S.: data curation, validation; Ł.K.: supervi- sion, writing—review and editing. All authors have read and agreed to the published version of the manuscript. Funding: This research was funded by ChM SP. Z O.O., Poland. Institutional Review Board Statement: The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board (or Ethics Committee) of Maria Sklodowska-Curie Memorial Cancer Center Ethics Committee in Gliwice (KB 430-15/17). Informed Consent Statement: Informed consent was obtained from all subjects involved in the study. Conﬂicts of Interest: The authors declare no conﬂict of interest. Appl. Sci. 2021, 11, 2176 13 of 14

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