Combination of Autologous Protein-Rich Fibrin and Bone Graft: An Invaluable Option for Reconstruction of Segmental Mandibular Defects

Distraction osteogenesis is an established technique for the lengthening of long bones and correction of selected craniofacial deformities. Regenerate osteoid bone matrix formed during the distraction phase is malleable and can recreate the three-dimensional form of native bones. Animal experiments and early clinical experience have confirmed that distraction osteogenesis can be used for the reconstruction of segmental bony defects. Herein we discuss the principles of distraction osteogenesis in reference to reconstruction of segmental bony defects and report its clinical application of the mandible continuity defects. Four patients (age, 7-83 years) with critical segmental mandibular defects (range, 3.5 cm-6.5 cm), resulting from ablative oncologic head and neck surgery underwent primary mandibular reconstruction by transport distraction osteogenesis. Two defects were at the angle and body region, one at the body, and the other at the parasymphysis and body region. Synthes Titanium Multi-vector and Leibinger Multi-guide distractors in bifocal (n = 2) and trifocal (n = 2) architecture were used after the stabilization of the segmental continuity defect using a defect-bridging mandibular reconstruction plate. Osteodistraction was carried out at a rate of 1 mm per day, with once or twice a day rhythm, after a 1-week latency period. The consolidation period was equal to the period of distraction. All patients tolerated the distraction procedure. Satisfactory bone formation was observed in two patients, and partial bone formation was seen in one patient. Treatment failure was encountered in one patient who had a second oral cavity primary tumor observed during the consolidation period, requiring interruption of the treatment sequence. Mandibular reconstruction with distraction osteogenesis is a potentially useful technique in selected patients with segmental mandibular continuity defects after ablative head and neck cancer surgery.

Primate mandibular reconstruction with prefabricated, vascularized tissue-engineered bone flaps and recombinant human bone morphogenetic protein-2 implanted in situ

Comparison of miniplates and biodegradable plates in reconstruction of the mandible with a fibular free flap

A preliminary clinical study of trifocal distraction osteogenesis for reconstruction of segmental mandibular defects

Free flap surgery is currently the only successful method used by surgeons to reconstruct critical-sized defects of the jaw, and is commonly used in patients who have had bony lesions excised due to oral cancer, trauma, infection or necrosis. However, donor site morbidity remains a significant flaw of this strategy. Various biomaterials have been under investigation in search of a suitable alternative for segmental mandibular defect reconstruction. Hydrogels are group of biomaterials that have shown their potential in various tissue engineering applications, including bone regeneration, both through in vitro and in vivo pre-clinical animal trials. This review discusses different types of hydrogels, their fabrication techniques, 3D printing, their potential for bone regeneration, outcomes, and the limitations of various hydrogels in preclinical models for bone tissue engineering. This review also proposes a modified technique utilizing the potential of hydrogels combined with scaffolds and cells for efficient reconstruction of mandibular segmental defects.

Reconstruction of Mandibular Segmental Defects Using the Guided-Bone Regeneration Technique With Polylactide Membranes and/or Autogenous Bone Graft: A Preliminary Study on the Influence of Membrane Permeability

Bone fusion of defect broken ends is the basis of the functional reconstruction of critical maxillofacial segmental bone defects. However, the currently available treatments do not easily achieve this goal. Therefore, this study aimed to fabricate 3D-printing titanium grid scaffolds, which possess sufficient pores and basic biomechanical strength to facilitate osteogenesis in order to accomplish bone fusion in mandibular segmental bone defects. The clinical trial was approved and supervised by the Medical Ethics Committee of the Chinese PLA General Hospital on March 28th, 2019 (Beijing, China. approval No. S2019–065–01), and registered in the clinical trials registry platform (registration number: ChiCTR2300072209). Titanium grid scaffolds were manufactured using selective laser melting and implanted in 20 beagle dogs with mandibular segmental defects. Half of the animals were treated with autologous bone chips and bone substances incorporated into the scaffolds; no additional filling was used for the rest of the animals. After 18 months of observation, radiological scanning and histological analysis in canine models revealed that the pores of regenerated bone were filled with titanium grid scaffolds and bone broken ends were integrated. Furthermore, three patients were treated with similar titanium grid scaffold implants in mandibular segmental defects; no mechanical complications were observed, and similar bone regeneration was observed in the reconstructed patients’ mandibles in the clinic. These results demonstrated that 3D-printing titanium grid scaffolds with sufficient pores and basic biomechanical strength could facilitate bone regeneration in large-segment mandibular bone defects.

Objective/Hypothesis: To demonstrate that the osteocutaneous radial forearm free flap provides equivalent functional outcomes and improved morbidity compared to the fibular free flap in mandibular reconstruction. Study Design: Retrospective review. Methods: There were 168 patients requiring free flap reconstruction of segmental mandibular defects between January 2001 and December 2008. Mean follow-up was 31 months for fibula free flap (FFF) (n = 117) and 20 months for osteocutaneous radial forearm free flaps (OCRFFF) (n = 51), reflecting an increasing use of forearms. Results: OCRFFF were more commonly used in older patients (mean 63.7 years vs. 59 years, P = .03). The majority (96.2%) of reconstruction was for malignant pathology. Flap failure was 3.4% for the fibula group and 3.9% in the forearm group. Malunion was infrequent (2.0% OCRFFF, 6.0% FFF, P = .26). Donor site complications were higher in the FFF group (4.3%) versus none in the OCRFF group (P = .13). Despite a high rate of long-term survival in this patient population (75% at 5 years for carcinoma), dental implants were rarely placed (2.3% of patients) and were more common in forearm than fibula free flaps. Functional outcomes demonstrated no significant difference between groups with respect to oral diet (FFF 72.6% vs. OCRFFF 79.1%, P = .49) or retained enterogastric feeding tube (20.9% OCRFFF vs. 27.4% FFF, P = .49). Conclusions: Osteocutaneous radial forearm flaps provide comparable functional outcomes with less morbidity compared to fibula free flaps for selected segmental mandibulectomy defects. The overall dental implantation rate was low and more commonly performed in osteocutaneous radial forearm flaps compared to fibula flaps. Laryngoscope, 2010

Mandibular segmental defect reconstruction is most often necessitated by tumor resection, trauma, infection, or osteoradionecrosis. The standard of care treatment for mandibular segmental defect repair involves using metallic plates to immobilize fibula grafts, which replace the resected portion of mandible. Surgical grade 5 titanium (Ti-6Al-4V) is commonly used to fabricate the fixture plate due to its low density, high strength, and high biocompatibility. One of the potential problems with mandibular reconstruction is stress shielding caused by a stiffness mismatch between the Titanium fixation plate and the remaining mandible bone and the bone grafts. A highly stiff fixture carries a large portion of the load (e.g., muscle loading and bite force), therefore the surrounding mandible would undergo reduced stress. As a result the area receiving less strain would remodel and may undergo significant resorption. This process may continue until the implant fails. To avoid stress shielding it is ideal to use fixtures with stiffness similar to that of the surrounding bone. Although Ti-6Al-4V has a lower stiffness (110 GPa) than other common materials (e.g., stainless steel, tantalum), it is still much stiffer than the cancellous (1.5–4.5 GPa) and cortical portions of the mandible (17.6–31.2 GPa). As a solution, we offer a nitinol in order to reduce stiffness of the fixation hardware to the level of mandible. To this end, we performed a finite element analysis to look at strain distribution in a human mandible in three different cases: I) healthy mandible, II) resected mandible treated with a Ti-6Al-4V bone plate, III) resected mandible treated with a nitinol bone plate. In order to predict the implant’s success, it is useful to simulate the stress-strain trajectories through the treated mandible. This work covers a modeling approach to confirm superiority of nitinol for mandibular reconstruction. Our results show that the stress-strain trajectories of the mandibular reconstruction using nitinol fixation is closer to normal than if grade 5 surgical titanium fixation is used.

PRP, cPRP, PRF, PRG, PRGF, FC … How to find your way in the jungle of platelet concentrates?

Introduction: Reconstruction of bony defects represents a challenging problem for the surgical community. Autologous bone grafting involves utilizing bone obtained from the same individual receiving the graft. Bone can be harvested from the mandibular symphysis (chin area). Autologous platelet rich-fibrin (PRF) is considered to be a healing biomaterial, which has been widely used for accelerating soft and hard tissue regeneration. The use of bone graft in combination with platelet rich-fibrin helps in rapid bone regeneration when compared to natural healing. Objectives: is to compare the effect of platelet rich-fibrin with and without autogenous bone graft on bone regeneration following enucleation of maxillary cysts. Materials and methods: Twenty-one patients with maxillary cysts had been treated with autogenous bone graft with platelet-rich fibrin versus platelet rich-fibrin without autogenous bone graft following cyst enucleation, and the follow up was done for 6 months using Cone Beam Computerized Tomography (CBCT) to evaluate bone regeneration in the defect site. Results:All groups showed increasing in bone density. Group A showed the best results with a mean 330.71, while Group B showed results with a mean 184. Group C showed results with a mean 117.71. Conclusions: PRF can be considered a healing biomaterial, as it features all the necessary parameters permitting bone regeneration without any adverse reaction. The addition of autogenous bone graft to PRF accelerates the regenerative capacity of bone. They give a predictable clinical and radiographic evidence of bone formation and faster healing than using PRF alone.

Medicine related osteonecrosis of jaw (MRONJ) is incidental in patients receiving certain bone modifying agents in oncology. These lesions may not respond to conservative management and aggravate. Autologous platelet derivatives contain bone growth factors, which help in bone regeneration. The aim of this pilot study is to develop protocol for treatment of refractory MRONJ with pizosurgical debridement and advanced platelet rich fibrin.In this feasibility study, refractory MRONJ lesions were treated by piezosurgical debridement and insertion of autologous advanced platelet rich fibrin in 15 patients. One patient had 2 lesion sites, so in all 16 MRONJ sites were treated. These patients were evaluated at the end of 1 month and 4 months for healing of MRONJ lesion. Statistical analysis was done by using Fisher test for response assessment in relation to variable. Eight lesions (50%) showed complete healing at the end of 1 month. At the end of 4 months 13 lesions (81.50%) were completely healed, 2 lesions (12.5%) were downgrades, and 1 lesion (6.25%) did not respond to treatment. Number of doses of bone modifying agent was only factor found associated with nonhealing of MRONJ when treated with this protocol.In this pilot study, feasibility of use of piezosurgical debridement and platelet rich fibrin was evaluated. The results of the study suggest complete healing can be achieved with this treatment protocol. Further research with increased sample size is warranted to determine optimum use of autologous platelet concentrates in treatment of MRONJ.

To investigate the feasibility of using computer-aided design (CAD) in double-step distraction osteogenesis in the reconstruction of mandibular segmental defects after tumor resection. Eight cases of unilateral mandibular segmental defects were reconstructed using distraction osteogenesis secondary to oncologic surgery, with the help of CT and CAD system. The mandibular body was lengthened first, and then the residual defect of mandibular ramus was restored using a distraction device. No incidence of infection or other complications were observed. The maximal amount of the lengthening reached 55 mm in the mandibular body, and 45 mm in the mandibular ramus. The average amount of the lengthening reached 49 mm in the mandibular body, and 36 mm in the mandibular ramus. The aesthetic and functional results of bone lengthening were excellent in all cases. The retractor was removed eight months postoperatively. Using CAD in double-step distraction osteogenesis in the reconstruction of unilateral mandibular segmental defects has the advantages of precise diagnosis, operation planning and assuring success of operation. It has the disadvantage of a long period for the overall treatment time.

A wide range of regenerative materials have been tried and tested in the treatment of furcation defects. Rosuvastatin (RSV) is a new synthetic, second-generation, sulfur-containing, hydrophilic statin with potent anti-inflammatory and osseodifferentiation mechanisms of action. Platelet-rich fibrin (PRF) is a platelet concentrate having sustained release of various growth factors with regenerative potential to treat periodontal defects. Porous hydroxyapatite (HA) bone grafting material has a clinically satisfactory response when used to fill periodontal intrabony defects. This double-masked randomized study is designed to evaluate the potency of a combination of 1.2 mg RSV in situ gel with a 1:1 mixture of autologous PRF and HA bone graft in the surgical treatment of mandibular Class II furcation defects compared with autologous PRF and HA bone graft placed after open-flap debridement (OFD). One hundred five mandibular furcation defects were treated with OFD + placebo gel (group 1), PRF + HA with OFD (group 2), or 1.2 mg RSV gel + PRF + HA with OFD (group 3). Clinical and radiologic parameters (i.e., probing depth [PD], relative vertical and relative horizontal clinical attachment level [rvCAL and rhCAL], intrabony defect depth, and percentage of defect fill) were recorded at baseline and 9 months postoperatively. Mean PD reduction was greater in group 2 (3.68 ± 1.07 mm) and group 3 (4.62 ± 1.03 mm) than group 1 (2.11 ± 1.25 mm), and mean rvCAL and rhCAL gain were greater in group 2 (3.31 ± 0.52 and 2.97 ± 0.56 mm, respectively) and group 3 (4.17 ± 0.70 and 4.05 ± 0.76 mm) compared with group 1 (1.82 ± 0.78 and 1.62 ± 0.64 mm). A significantly greater percentage of mean bone fill was found in group 2 (54.69% ± 1.93%) and group 3 (61.94% ± 3.54%) compared with group 1 (10.09% ± 4.28%). Treatment of furcation defects with 1.2 mg RSV in situ gel combined with autologous PRF and porous HA bone graft results in significant improvements of clinical and radiographic parameters compared with OFD alone. These results imply that the combination of RSV, PRF, and HA has synergistic effects, explaining their role as a regenerative material in the treatment of furcation defects.

The purpose of this study was to compare spontaneous bone regeneration, osteoconduction, and bone autografting in critical size calvarial and mandibular defects (defects which do not heal spontaneously during the lifetime of the animal) that were protected from soft-tissue interposition. Eighteen adult mongrel dogs underwent osteotomies to create a unilateral 30-mm segmental defect in the midbody of the edentulated right mandible and bilateral 15-mm x 20-mm full-thickness window defects in the parietal bones. The defects were either left empty, implanted with coralline hydroxyapatite (HA) blocks, or autografted with iliac cancellous bone. All defects were protected with a macroporous titanium mesh and the segmental mandibular defects were additionally stabilized by internal plate fixation. Specimens were retrieved after 2 and 4 months and three undecalcified longitudinal central sections including the osteotomy interfaces were prepared from each specimen for histometry and histology. Sections were analyzed for volume fractions of bone, soft tissue, and implant using scanning electron microscopy, backscatter electron imaging and histometric computer software. In the mandibular model, the empty defects exhibited the greatest amount of bone formation after 4 months (47.3 percent), which was greater than the amount of bone in the autografted group (34.8 percent) and significantly greater than the amount of bone within the hydroxyapatite implants (19.0 percent, p < 0.05). In the cranial defects, the autografted specimens demonstrated the greatest volume fraction of bone after 4 months (27.3 percent), which was significantly greater than within both the empty defects (18.2 percent, p < 0.05) and the hydroxyapatite implants (18.2 percent, p < 0.05). New bone formation in the mandibular defects united the cut ends at 4 months regardless of treatment and originated predominantly from the periosteum which remained present only along the alveolar border after surgical closure. In the calvarial defects, periosteum was not preserved and bone regenerated centripetally, originating from the diploë without any evidence of dural osteogenesis. Bone bridging was incomplete in the empty cranial defects at 4 months. In both the mandibular and cranial specimens, new bone at 2 months was a mixture of woven and parallel fibered bone. At 4 months, the new bone had remodeled almost entirely into mature Haversian bone. This study demonstrated a remarkable ability of defect protection with a macroporous protective sheet to facilitate bone regeneration in critical size mandibular and cranial bone defects. When active osteogenic periosteum was present, as in our mandibular model, we concluded that defect protection alone was sufficient to allow for healing even of critical size defects. When periosteum was absent as in our cranial defects, the limited spontaneous bone formation benefited from the added contributions of cancellous grafting and osteoconductive implants, both of which promoted bone bridging across the defects. We suggest that in the future a resorbable macroporous protective sheet would be advantageous in comparison to a titanium mesh to facilitate bone regeneration by preventing soft-tissue prolapse and allowing the migration of mesenchymal cells and the proliferation of blood vessels from the adjacent soft tissues into the bone defect. Finally, this study identified the need to differentiate critical size defects into those with and without defect protection and periosteum.