A Preclinical Trial Protocol Using an Ovine Model to Assess Scaffold Implant Biomaterials for Repair of Critical-Sized Mandibular Defects.

The present work describes a preclinical trial (in silico, in vivo and in vitro) protocol to assess the biomechanical performance and osteogenic capability of 3D-printed polymeric scaffolds implants used to repair partial defects in a sheep mandible. The protocol spans multiple steps of the medical device development pipeline, including initial concept design of the scaffold implant, digital twin in silico finite element modeling, manufacturing of the device prototype, in vivo device implantation, and in vitro laboratory mechanical testing. First, a patient-specific one-body scaffold implant used for reconstructing a critical-sized defect along the lower border of the sheep mandible ramus was designed using on computed-tomographic (CT) imagery and computer-aided design software. Next, the biomechanical performance of the implant was predicted numerically by simulating physiological load conditions in a digital twin in silico finite element model of the sheep mandible. This allowed for possible redesigning of the implant prior to commencing in vivo experimentation. Then, two types of polymeric biomaterials were used to manufacture the mandibular scaffold implants: poly ether ether ketone (PEEK) and poly ether ketone (PEK) printed with fused deposition modeling (FDM) and selective laser sintering (SLS), respectively. Then, after being implanted for 13 weeks in vivo, the implant and surrounding bone tissue was harvested and microCT scanned to visualize and quantify neo-tissue formation in the porous space of the scaffold. Finally, the implant and local bone tissue was assessed by in vitro laboratory mechanical testing to quantify the osteointegration. The protocol consists of six component procedures: (i) scaffold design and finite element analysis to predict its biomechanical response, (ii) scaffold fabrication with FDM and SLS 3D printing, (iii) surface treatment of the scaffold with plasma immersion ion implantation (PIII) techniques, (iv) ovine mandibular implantation, (v) postoperative sheep recovery, euthanasia, and harvesting of the scaffold and surrounding host bone, microCT scanning, and (vi) in vitro laboratory mechanical tests of the harvested scaffolds. The results of microCT imagery and 3-point mechanical bend testing demonstrate that PIII-SLS-PEK is a promising biomaterial for the manufacturing of scaffold implants to enhance the bone-scaffold contact and bone ingrowth in porous scaffold implants. MicroCT images of the harvested implant and surrounding bone tissue showed encouraging new bone growth at the scaffold-bone interface and inside the porous network of the lattice structure of the SLS-PEK scaffolds.

Medial Femoral Condyle Periosteal Free Flap for Bone Coverage Following Debridement of Intermediate-Stage Osteoradionecrosis of the Jaw.

STUDY DESIGN: Case report. Osteoradionecrosis (ORN) of the jaw is a potentially devastating consequence of head and neck irradiation. The progression of ORN can lead to loss of bone, teeth, soft tissue necrosis, pathologic fracture, and oro-cutaneous fistula. Reconstructive surgery has mostly been reserved for late-stage disease where segmental resections are frequently necessary. Evidence is emerging to support earlier treatment in the form of debridement in combination with soft tissue free flaps for intermediate-stage ORN. The authors present a case of a 76-year-old male with persistent Notani 2 ORN of the mandible, treated with surgical removal of all remaining mandibular teeth, transoral debridement of all necrotic mandibular bone, and bone coverage with a left medial femoral condyle (MFC) periosteal free flap based on the descending genicular artery. Treatment was uneventful both intraoperatively and postoperatively. Since surgery (15 mo) the patient has remained free from clinical and radiologic signs of ORN. The MFP periosteal free flap provided an excellent result with minimal surgical complexity and morbidity in this case. Such treatment at an intermediate stage likely results in a reduction in segmental resections, less donor site morbidity, less operative time, less overall treatment time, and possibly fewer postoperative complications compared with the status quo.

Novel Sheep Model to Assess Critical-Sized Bone Regeneration with Periosteum for In Vivo Bioreactors.

Considerable research is being undertaken to develop novel biomaterials-based approaches for surgical reconstruction of bone defects. This extends to three-dimensional (3D) printed materials that provide stable, structural, and functional support in vivo. However, few preclinical models can simulate in vivo human biological conditions for clinically relevant testing. In this study we describe a novel ovine model that allows evaluation of in vivo osteogenesis via contact with bone and/or periosteum interfaced with printed polymer bioreactors loaded with biomaterial bone substitutes. The infraspinous scapular region of 14 Dorset cross sheep was exposed. Vascularized periosteum was elevated either attached to the infraspinatus muscle or separately. In both cases, the periosteum was supplied by the periosteal branch of the circumflex scapular vessels. In eight sheep, a 3D printed 4-chambered polyetheretherketone bioreactor was wrapped circumferentially in vascularized periosteum. In 6 sheep, 12 double-sided 3D printed 2-chambered polyetherketone bioreactors were secured to the underlying bone allowing direct contact with the bone on one side and periosteum on the other. Our model enabled simultaneous testing of up to 24 (12 double-sided) 10 × 10 × 5 mm bioreactors per scapula in the flat contact approach or a single 40 × 10 mm four-chambered bioreactor per scapula using the periosteal wrap. De novo bone growth was evaluated using histological and radiological analysis. Of importance, the experimental model was well tolerated by the animals and provides a versatile approach for comparing the osteogenic potential of cambium on the bone surface and elevated with periosteum. Furthermore, the periosteal flaps were sufficiently large for encasing bioreactors containing biomaterial bone substitutes for applications such as segmental mandibular reconstruction.

Surgical and health related quality of life outcomes following treatment with zygomatic implant perforated (ZIP) flaps.

BACKGROUND: The zygomatic implant perforated (ZIP) flap is a novel approach to the challenge of reconstructing the maxilla. We report on our experience using the ZIP flap technique for patients undergoing infrastructure maxillectomy at Chris O'Brien Lifehouse, Sydney, Australia. METHODS: Thirteen patients who underwent a ZIP flap reconstruction between August 2019 and August 2021 were identified. Demographic, surgical, and histopathological information was collected. Health Related Quality of Life (HRQOL) was assessed using the FACE-Q Head and Neck Cancer module, the M.D. Anderson Dysphagia Inventory, and the Speech Handicap Index. RESULTS: A total of 44 zygomatic implants were placed, of which 42 (95%) survived. The median time from surgery to dental rehabilitation was 35 days. HRQOL data was available for nine patients over 24 months, demonstrating improved speech and swallowing outcomes over the follow up period. CONCLUSIONS: The ZIP flap is a reproducible surgical technique that facilitates rapid dental rehabilitation post infrastructure maxillectomy.

A Comparison of In Vivo Bone Tissue Generation Using Calcium Phosphate Bone Substitutes in a Novel 3D Printed Four-Chamber Periosteal Bioreactor.

Autologous bone replacement remains the preferred treatment for segmental defects of the mandible; however, it cannot replicate complex facial geometry and causes donor site morbidity. Bone tissue engineering has the potential to overcome these limitations. Various commercially available calcium phosphate-based bone substitutes (Novabone®, BioOss®, and Zengro®) are commonly used in dentistry for small bone defects around teeth and implants. However, their role in ectopic bone formation, which can later be applied as vascularized graft in a bone defect, is yet to be explored. Here, we compare the above-mentioned bone substitutes with autologous bone with the aim of selecting one for future studies of segmental mandibular repair. Six female sheep, aged 7-8 years, were implanted with 40 mm long four-chambered polyether ether ketone (PEEK) bioreactors prepared using additive manufacturing followed by plasma immersion ion implantation (PIII) to improve hydrophilicity and bioactivity. Each bioreactor was wrapped with vascularized scapular periosteum and the chambers were filled with autologous bone graft, Novabone®, BioOss®, and Zengro®, respectively. The bioreactors were implanted within a subscapular muscle pocket for either 8 weeks (two sheep), 10 weeks (two sheep), or 12 weeks (two sheep), after which they were removed and assessed by microCT and routine histology. Moderate bone formation was observed in autologous bone grafts, while low bone formation was observed in the BioOss® and Zengro® chambers. No bone formation was observed in the Novabone® chambers. Although the BioOss® and Zengro® chambers contained relatively small amounts of bone, endochondral ossification and retained hydroxyapatite suggest their potential in new bone formation in an ectopic site if a consistent supply of progenitor cells and/or growth factors can be ensured over a longer duration.

Outcomes of immediate dental implants in vascularised bone flaps for mandibular reconstruction.

BACKGROUND: The aim of this study is to assess the outcomes of immediate implant placement for dental rehabilitation following mandibular reconstruction with vascularised bone flaps in a single Australian tertiary cancer centre. METHODS: A retrospective analysis of patients who underwent immediate dental implant or delayed placement in vascularised bone flaps was performed. Primary outcome measures assessed included the number of implants placed, operative time, complication rates, time to radiotherapy initiation, dental rehabilitation rates and time to dental rehabilitation. RESULTS: In total, 187 dental implants were placed in 52 patients, of which 34 patients underwent immediate implant placement and 18 had delayed implant placement. There were no significant differences in the postoperative complication rate (32% immediate vs. 33% delayed, P = 0.89) or time to postoperative radiotherapy (median 42 days immediate vs. 47 days delayed, P = 0.24). Dental rehabilitation was achieved in 62% of the immediate cohort versus 78% of the delayed cohort. The time to be fitted with a dental prosthesis was significantly shorter in the immediate cohort (median 150 days immediate vs. 843 days delayed, P = 0.002). CONCLUSIONS: The placement of immediate dental implants at the time of primary reconstruction of the mandible is a safe procedure and facilitates timely dental rehabilitation.

Effect of operative time on complications associated with free flap reconstruction of the head and neck.

OBJECTIVE: To evaluate whether prolonged operative time is negatively associated with post-operative complications and length of stay in patients undergoing microvascular free flap reconstruction for complex head and neck defects. METHODS: 342 consecutive patients undergoing microvascular reconstruction for head and neck defects between 2017-2019 at a single institution were evaluated. Operative outcomes and operative time were compared whilst controlling for patient and treatment related factors. RESULTS: Mean operative time was 551 min and length of stay was 16.2 days. An 11% increase in the risk of a post-operative complication was observed for every additional hour of operative time (OR 1.11, 95% CI 1.03-1.21, p = 0.011) after adjusting for patient and treatment factors. A cut-off of 9 h yielded a 92% increase in complications on either side of this (OR 1.92, 95% CI 1.18-3.13, p = 0.009). Increased operative time was also associated with increased length of stay and return to theatres, but not medical complications. CONCLUSION: Prolonged operative time is significantly associated with increased surgical complications, length of stay and return to theatres when performing microvascular reconstructive surgery for head and neck defects.

Expanding the digital workflow for a prefabricated prelaminated fibula flap: A dental technique.

The workflow for a prefabricated prelaminated fibula free flap has been almost entirely digitized. One of the last 2 remaining steps is the impression making in stage 1 surgery. This article describes a novel computed-tomography based digital scanning technique with an assessment of the resultant accuracy.

Effect of Radiotherapy on Functional and Health-Related Quality of Life Outcomes after Jaw Reconstruction.

Long-term health-related quality of life (HRQOL) and functional outcomes following mandibular and maxillary reconstruction are lacking. To determine these outcomes, a cross-sectional study of patients with a history of cancer who underwent jaw reconstruction was undertaken. Participants were identified from a database of jaw reconstruction procedures at the Chris O'Brien Lifehouse (Sydney, Australia). Eligible patients had at least one month follow-up, were aged ≥18 years at surgery, and had history of malignancy. HRQOL was measured using the FACE-Q Head and Neck Cancer Module (FACE-Q H&N). Functional outcomes were measured using the FACE-Q H&N, MD Anderson Dysphagia Inventory (MDADI) and Speech Handicap Index (SHI). Ninety-seven questionnaires were completed (62% response rate). Mean age of respondents was 63.7 years, 61% were male, and 64% underwent radiotherapy. Treatment with radiotherapy was associated with worse outcomes across 10/14 FACE-Q H&N scales, three MDADI subscales and one composite score, and the SHI. Mean differences in scores between irradiated and non-irradiated patients exceeded clinically meaningful differences for the MDADI and SHI. Issues with oral competence, saliva, speaking, and swallowing worsened with increasing time since surgery. Younger patients reported greater concerns with appearance, smiling, speaking, and cancer worry. Women reported greater concerns regarding appearance and associated distress. History of radiotherapy substantially impacts HRQOL and function after jaw reconstruction. Age at surgery and gender were also predictors of outcomes and associated distress. Pre-treatment counselling of patients requiring jaw reconstruction may lead to improved survivorship for patients with head and neck cancer.

Patient specific implant with high condylar neck osteotomy for temporomandibular joint preservation in segmental mandibulectomy.

STUDY DESIGN: Letter to the Editor. OBJECTIVE: Disarticulation may be considered during segmental mandibulectomy where margins necessitate high condylar neck osteotomy. Although a number of techniques have been reported for reconstruction of the condyle, successful preservation of normal joint anatomy, where possible, should be considered as a superior alternative. This report demonstrates a safe and predictable approach to condylar head preservation with high condylar neck osteotomy. METHODS: We present two cases of native TMJ preservation with a very short salvageable condylar component utilising 3D-printed patient specific cutting guides and implants. RESULTS: The condyle preserving reconstructive technique described successfully preserves the capsule of the TMJ, and with careful execution can preserve the intra-articular components of the joint and their relationships to each other. Both patients have experienced excellent outcomes to date. CONCLUSIONS: As opposed to disarticulation reconstructions, this technique is more likely to achieve long-term normal occlusion, maintain normal alignment of reconstructed segments, and preserve condylar translation as opposed to simple hinging, in addition to avoiding the potential pitfalls of alternative techniques.

Health-related quality of life in maxillectomy patients undergoing dentoalveolar rehabilitation.

OBJECTIVES: Surgical resection of the maxilla impairs aesthetics, speech, swallowing, and mastication. Maxillary reconstruction is increasingly performed with virtual surgical planning (VSP) to enhance functional dental rehabilitation with a conventional denture or osseointegrated implants. The aim of this study was to determine whether dental status and VSP is associated with health-related quality of life (HRQOL) and function in patients who have undergone maxillectomy. MATERIALS AND METHODS: A cross-sectional study was conducted among patients who underwent free flap reconstruction or obturation of the maxilla between July 2009 and December 2020. The FACE-Q Head and Neck Cancer (FACE-Q) module, M.D. Anderson Dysphagia Inventory (MDADI), and Speech Handicap Index (SHI) were used to evaluate HRQOL. RESULTS: Forty-three patients (response rate 59%) completed questionnaires and 48% underwent dental rehabilitation. In Okay Class II and III defects, adjusting for the effect of radiotherapy and time from surgery, there was a positive association between denture status and FACE-Q smiling (p = 0.020), eating (p = 0.012), smiling (p = 0.015), and MDADI global (p = 0.015), emotional (p = 0.027), functional (p = 0.028), and composite (p = 0.029) scores. VSP was associated with FACE-Q swallowing (p = 0.005), drooling (p = 0.030), eating (p = 0.008), smiling (p = 0.021), MDADI global (p = 0.017), emotional (p = 0.041), functional (p = 0.040), composite (p = 0.038), and SHI total scores (p = 0.042). CONCLUSIONS: Dentoalveolar rehabilitation and VSP were associated with higher HRQOL scores relating to eating and drinking, smiling, and speaking.

Dentoalveolar outcomes in maxillary reconstruction: A retrospective review of 85 maxillectomy reconstructions.

BACKGROUND: Although microvascular free flaps are often used to reconstruct maxillary defects, dentoalveolar rehabilitation is arguably less common despite its importance to midface function and aesthetics. The aim of this study is to review the contemporary management of maxillary defects in a single quaternary referral institution to identify factors that assist or impede dentoalveolar rehabilitation. METHODS: A retrospective review of maxillary reconstructions performed between February 2017 and December 2020 was performed. Patient characteristics, defect classification, operative techniques, complications and dentoalveolar outcomes were recorded. RESULTS: A total of 85 maxillary reconstructions were performed in 73 patients. Of the 64 patients where dental rehabilitation was required, 31 received a functional denture (48%) with 24 (38%) being implant-retained. Significant predictors of successful rehabilitation included the use of virtual surgical planning (VSP; 86% vs. 25%, p < 0.001), preoperative prosthodontic assessment (82% vs. 21%, p < 0.001), prefabrication (100% vs. 40%, p = 0.002) and use of the zygomatic implant perforator flap technique (100% vs. 39%, p = 0.001). Preoperative prosthodontic consultation was associated with 21-fold increase in the odds of rehabilitation (odds ratio 20.9, 95% confidence interval 6.54-66.66, p < 0.005). CONCLUSION: Preoperative prosthodontic evaluation, VSP and reconstructive techniques developed to facilitate implant placement are associated with increased dental rehabilitation rates. Despite using an institutional algorithm, functional dentures are frequently prevented by factors including soft tissue constraints, disease recurrence and patient motivation.

Maxillofacial reconstruction with prefabricated prelaminated osseous free flaps.

BACKGROUND: The prefabricated fibula flap is an advanced method of occlusal-based reconstruction that combines placement of osseointegrated dental implants with prelamination, using a split skin graft on the fibula, weeks prior to the definitive reconstruction. This approach is resource intensive but has several advantages including eliminating the delay from reconstruction to dental rehabilitation. METHODS: A retrospective cohort study of all prefabricated fibula flaps used for mandible and maxillary reconstruction from 2012 to 2020 was performed. Outcome measures were implant survival, implant utilization and functional dental rehabilitation. RESULTS: A total of 17 prefabricated fibula flaps were performed including two analogue and 15 digital plans. There were nine maxillary and eight mandibular reconstructions, of which 11 were primary and seven were secondary. There were no free flap failures. A total of 65 implants were placed (average 3.8, median 3 implants). There was one implant failure at 6 years giving a 1.5% failure rate. There was 91% implant utilization and 94% functional dental rehabilitation. CONCLUSION: The prefabricated fibula flap provides outstanding dental rehabilitation in well-selected patients.

Occlusal-based planning for dental rehabilitation following segmental resection of the mandible and maxilla.

Reconstruction of the maxilla and mandible incorporating a dental prosthesis supported by dental implants is a complex process but has tremendous benefit to patient rehabilitation following ablative procedures. This study presents a protocol that can be used to aid other institutions to provide the highest standard of reconstruction.