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.

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.

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.

Viral Integration Plays a Minor Role in the Development and Prognostication of Oral Squamous Cell Carcinoma.

Viruses are well known drivers of several human malignancies. A causative factor for oral cavity squamous cell carcinoma (OSCC) in patients with limited exposure to traditional risk factors, including tobacco use, is yet to be identified. Our study aimed to comprehensively evaluate the role of viral drivers in OSCC patients with low cumulative exposure to traditional risk factors. Patients under 50 years of age with OSCC, defined using strict anatomic criteria were selected for WGS. The WGS data was interrogated using viral detection tools (Kraken 2 and BLASTN), together examining >700,000 viruses. The findings were further verified using tissue microarrays of OSCC samples using both immunohistochemistry and RNA in situ hybridisation (ISH). 28 patients underwent WGS and comprehensive viral profiling. One 49-year-old male patient with OSCC of the hard palate demonstrated HPV35 integration. 657 cases of OSCC were then evaluated for the presence of HPV integration through immunohistochemistry for p16 and HPV RNA ISH. HPV integration was seen in 8 (1.2%) patients, all middle-aged men with predominant floor of mouth involvement. In summary, a wide-ranging interrogation of >700,000 viruses using OSCC WGS data showed HPV integration in a minority of male OSCC patients and did not carry any prognostic significance.

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.

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.

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.

Tracheostomy in free-flap reconstruction of the oral cavity: can it be avoided? A cohort study of 187 patients.

BACKGROUND: Head and neck surgeons are moving away from routine tracheostomy in free-flap reconstruction. We reviewed prophylactic tracheostomy use in patients undergoing oral cavity or oropharynx free-flap reconstruction to identify patient groups who avoided tracheostomy. Secondary aims were to describe complications associated with and without tracheostomy. METHODS: A retrospective cohort study was undertaken, using a prospectively maintained database. Inclusion criteria was free-flap reconstruction for an oral cavity or oropharyngeal defect, excluding partial or total laryngectomy. Variables collected included demographics, comorbidity, American Society of Anesthesiologists grade, Charlson Comorbidity Index, tumour site and subsite, extent of resection, surgery duration, tracheostomy, complications, return to theatre and re-intubation. RESULTS: A total of 344 head and neck free-flap reconstructions were performed between January 2017 and July 2019. A total of 164 (87.7%) oral cavity and 23 (12.3%) oropharyngeal reconstructions were included totalling 187 free flaps. A total of 107 (57.2%) were males and 80 (42.8%) females, mean age 62.4 years (range 21-89). Of 187 patients, 100 (53.5%) underwent prophylactic tracheostomy at time of reconstruction. Longer operative time (P < 0.001), resection site (P < 0.001), number of subsites resected (P = 0.007), segmental mandibulectomy (P = 0.04), lip-split (P = 0.05), floor of mouth resection (P < 0.001), lingual release (P = 0.007), glossectomy (P < 0.001), extent of tongue resection (P < 0.001), extent of hard palate resection (P = 0.04), soft palate resection (P < 0.001) and double free-flap reconstruction (P = 0.04) were associated with tracheostomy use. CONCLUSION: A personalized approach to postoperative airway management allowed almost half of our cohort to avoid tracheostomy. In high-volume institutions with the necessary expertise and support, appropriately selected patients may be safely managed without routine tracheostomy.

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.

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.