Critical-sized Mandibular Defect Research Articles

3D-printed scaffold combined to 2D osteoinductive coatings to repair a critical-size mandibular bone defect.

The reconstruction of large bone defects (12 cm3) remains a challenge for clinicians. We developed a new critical-size mandibular bone defect model on a minipig, close to human clinical issues. We analyzed the bone reconstruction obtained by a 3D-printed scaffold made of clinical-grade polylactic acid (PLA), coated with a polyelectrolyte film delivering an osteogenic bioactive molecule (BMP-2). We compared the results (computed tomography scans, microcomputed tomography scans, histology) to the gold standard solution, bone autograft. We demonstrated that the dose of BMP-2 delivered from the scaffold significantly influenced the amount of regenerated bone and the repair kinetics, with a clear BMP-2 dose-dependence. Bone was homogeneously formed inside the scaffold without ectopic bone formation. The bone repair was as good as for the bone autograft. The BMP-2 doses applied in our study were reduced 20- to 75-fold compared to the commercial collagen sponges used in the current clinical applications, without any adverse effects. Three-dimensional printed PLA scaffolds loaded with reduced doses of BMP-2 may be a safe and simple solution for large bone defects faced in the clinic.

Local administration of HMGB-1 promotes bone regeneration on the critical-sized mandibular defects in rabbits

Reconstruction of a critical-sized osseous defect is challenging in maxillofacial surgery. Despite novel treatments and advances in supportive therapies, severe complications including infection, nonunion, and malunion can still occur. Here, we aimed to assess the use of a beta-tricalcium phosphate (β-TCP) scaffold loaded with high mobility group box-1 protein (HMGB-1) as a novel critical-sized bone defect treatment in rabbits. The study was performed on 15 specific pathogen-free New Zealand rabbits divided into three groups: Group A had an osseous defect filled with a β-TCP scaffold loaded with phosphate-buffered saline (PBS) (100 µL/scaffold), the defect in group B was filled with recombinant human bone morphogenetic protein 2 (rhBMP-2) (10 µg/100 µL), and the defect in group C was loaded with HMGB-1 (10 µg/100 µL). Micro-computed tomography (CT) examination demonstrated that group C (HMGB-1) showed the highest new bone volume ratio, with a mean value of 66.5%, followed by the group B (rhBMP-2) (31.0%), and group A (Control) (7.1%). Histological examination of the HMGB-1 treated group showed a vast area covered by lamellar and woven bone surrounding the β-TCP granule remnants. These results suggest that HMGB-1 could be an effective alternative molecule for bone regeneration in critical-sized mandibular bone defects.

Real-time assessment of guided bone regeneration in critical size mandibular bone defects in rats using collagen membranes with adjunct fibroblast growth factor-2

Background/purposeFibroblast growth factor-2 (FGF-2) regulates bone formation. The concept of guided bone regeneration using a resorbable collagen membrane (RCM) is generally accepted in implant dentistry. This study aimed to investigate the bone healing pattern in rat mandibular bone defects in real-time with and without RCM containing FGF-2 (RCM/FGF-2). Materials and methodsCritical-size circular bone defects (4.0 mm diameter) were created on both sides of the rat mandibular bone. The defects were randomly divided into the following groups: control, RCM alone, RCM containing low (0.5 μg) or high (2.0 μg) concentration of FGF-2. We performed real-time in vivo micro-computerized tomography scans at the baseline and at 2, 4, and 6 weeks, and measured the volume of newly formed bone (NFB), bone mineral density (BMD) of NFB, and the closure percentage of the NFB area. At 6 weeks, the mandibular specimens were assessed histologically and histomorphometrically to evaluate the area of new bone regeneration. ResultsReal-time assessment revealed a significant increase in the volume, BMD, and closure percentage of the NFB area in the RCM/FGF-2-treated groups than that in the control and RCM groups. In the H-FGF-2 group, the volume and BMD of NFB exhibited a significant increase at 6 weeks than that at the baseline. Histological evaluation revealed the presence of osteoblasts, osteocytes, and blood vessels within the NFB. ConclusionThe real-time in vivo experiment demonstrated that RCM/FGF-2 effectively promoted bone regeneration within the critical-size mandibular defects in rats and verified new bone formation starting in the early postoperative phase.

Regeneration of critical-sized mandibular defect using a 3D-printed hydroxyapatite-based scaffold: An exploratory study.

Three-dimensional (3D) printing has become an available technology to fabricate customized tissue engineering scaffolds with delicate architecture. This exploratory study aimed to evaluate the potential of a 3D-printed hydroxyapatite-based scaffold as a biomaterial for obtaining guided bone regeneration (GBR) in vivo. Scaffolds composed of 90% hydroxyapatite and 10% poly(lactic-co-glycolic acid) were printed using a microextrusion process to fit 4mm diameter and 0.5mm thick through-and-through osseous defects on the mandibular ramus of rats, with unfilled defects serving as controls. Specimens were analyzed for regeneration-associated gene expression on day 7, and micro-computed tomography (micro-CT) and histology assessments were carried out on day 28. The scaffolds were 3.56 ± 0.43mm (x-axis) and 4.02 ± 0.44mm (y-axis) in diameter and 0.542 ± 0.035mm thick (z-axis), with a mean pore size of 0.420 ± 0.028×0.328 ± 0.005 mm2 . Most scaffolds fit the defects well. Type I collagen, VEGF, and Cbfa1 were upregulated in the scaffold-treated defects by day 7. By day 28, de novo osteogenesis and scaffold-tissue integration were evident in the scaffold-treated defects, and entire mineralized tissue, as well as newly formed bone, was significantly promoted, as seen in the micro-CT and histologic analyses. The 3D-printed hydroxyapatite-based scaffold showed acceptable dimensional stability and demonstrated favorable osteoregenerative capability that fulfilled the need for GBR.

Critical-sized mandibular defect reconstruction using human dental pulp stem cells in a xenograft model-clinical, radiological, and histological evaluation.

This research evaluated clinical, histological, and radiological osseous regeneration in a critical-sized bilateral cortico-medullary osseous defect in model rabbits from New Zealand after receiving a hydroxyapatite matrix and polylactic polyglycolic acid (HA/PLGA) implanted with human dental pulp stem cells (DPSCs). Eight New Zealand rabbits with bilateral mandibular critical-sized defects were performed where one side was treated with an HA/PLGA/DPSC matrix and the other side only with an HA/PLGA matrix for 4weeks. An osseointegration was clinically observed as well as a reduction of 70% of the surgical lumen on one side and a 35% on the other. Histologically, there was neo-bone formation in HA/PLGA/DPSC scaffold and angiogenesis. A bone radiodensity (RD) of 80% was radiologically observed achieving density levels similar to mandibular bone, while the treatment with HA/PLGA matrix achieves RD levels of 40% on its highest peaks. HA/PLGA/DPSC scaffold was an effective in vivo method for mandibular bone regeneration in critical-sized defects induced on rabbit models.

Xenogeneic mesenchymal stem cell transplantation for mandibular defect regeneration.

It is commonly accepted that xenogeneic stem cell transplantation for tissue engineering is faced with host immune rejection. Using a rat critical-size mandibular defect model, this study examined whether the immune rejection can be evaded by diminishing T-cell immunity. To examine donor cell survival and host immune reaction, pig bone marrow-derived mesenchymal stem cells (BM-MSCs) were labeled with CM-DiI, loaded onto gelatin sponge (5×106 cells/scaffold), and transplanted into 5-mm mandibular defects of immunocompetent and T cell-deficient athymic rats. To examine the effects of xenogeneic BM-MSCs on bone regeneration, athymic rats undergone the same surgeries were terminated at post-operative weeks 1, 3, and 6. Control rats underwent the same jaw surgery without BM-MSC transplantation. The density of CM-DiI-labeled BM-MSCs decreased with time in both strains of rats. Although it was substantially higher in athymic rats than in immunocompetent rats at post-operative day 1, by day 3-7 the density became comparable between the two strains of rats. Apoptosis reflected by cleaved Caspase-3 staining was low in both strains. Stronger infiltration of neutrophils, macrophages, B cells and CD8+ T cells was found in MSC-treated animals. In athymic rats, infiltration of neutrophils and macrophages was strong, but it occurred later than that in immunocompetent rats. While bone volume fraction significantly increased with time (P<.001), no difference was found between MSC-treated and control groups. Even in hosts with deficient T-cell immunity, xenogeneic BM-MSC transplantation into mandibular critical-sized defects still faces challenges from host innate immunity, which compromises their regenerative efficacy.

3D printed composite scaffolds with dual small molecule delivery for mandibular bone regeneration

Functional reconstruction of craniomaxillofacial defects is challenging, especially for the patients who suffer from traumatic injury, cranioplasty, and oncologic surgery. Three-dimensional (3D) printing/bioprinting technologies provide a promising tool to fabricate bone tissue engineering constructs with complex architectures and bioactive components. In this study, we implemented multi-material 3D printing to fabricate 3D printed PCL/hydrogel composite scaffolds loaded with dual bioactive small molecules (i.e. resveratrol and strontium ranelate). The incorporated small molecules are expected to target several types of bone cells. We systematically studied the scaffold morphologies and small molecule release profiles. We then investigated the effects of the released small molecules from the drug loaded scaffolds on the behavior and differentiation of mesenchymal stem cells (MSCs), monocyte-derived osteoclasts, and endothelial cells. The 3D printed scaffolds, with and without small molecules, were further implanted into a rat model with a critical-sized mandibular bone defect. We found that the bone scaffolds containing the dual small molecules had combinational advantages in enhancing angiogenesis and inhibiting osteoclast activities, and they synergistically promoted MSC osteogenic differentiation. The dual drug loaded scaffolds also significantly promoted in vivo mandibular bone formation after 8 week implantation. This work presents a 3D printing strategy to fabricate engineered bone constructs, which can likely be used as off-the-shelf products to promote craniomaxillofacial regeneration.

Injectable hydrogel delivering bone morphogenetic protein-2, vascular endothelial growth factor, and adipose-derived stem cells for vascularized bone tissue engineering

We aimed to evaluate the integration of stem cells with injectable microspheres loaded with growth factors using a chitosan (CS) scaffold to promote healthy bone regeneration. We prepared and injected CS scaffolds containing adipose-derived stem cell (ADSC)-, vascular endothelial growth factor (VEGF)-, and bone morphogenetic protein-2 (BMP-2)-loaded nanohydroxyapatite (nHA)/poly lactic-co-glycolic acid microspheres (PLGAs) into critical-sized mandibular bone defects in rabbits. This injectable hydrogel displayed excellent physicochemical properties and degradability and achieved sustainable release and bioactivity preservation for both BMP-2 and VEGF. Computed tomography imaging and gross and histological observations indicated that bone defect cavities in the control group did not narrow and were filled with granulation tissue. Limited new bone formation for the first 12 weeks post-operation was observed in the defect cavities of the VEGF group; the scaffold degraded gradually and was replaced with fibrous connective tissue. In the BMP-2 or BMP-2/VEGF groups, bone defect cavities narrowed with time and healed completely after 12 weeks; scaffolds gradually degraded and infiltrated tightly into the surrounding tissues. Overall, the BMP-2/VEGF group demonstrated greater new bone formation, faster healing, and better callus remodeling. Simultaneous application of VEGF and BMP-2, therefore, promoted ossification and vascularization in critical-sized rabbit mandibular bone defects.

Early therapeutic effect of platelet-rich fibrin combined with allogeneic bone marrow-derived stem cells on rats' critical-sized mandibular defects.

Critically sized bone defects represent a significant challenge to orthopaedic surgeons worldwide. These defects generally result from severe trauma or resection of a whole large tumour. Autologous bone grafts are the current gold standard for the reconstruction of such defects. However, due to increased patient morbidity and the need for a second operative site, other lines of treatment should be introduced. To find alternative unconventional therapies to manage such defects, bone tissue engineering using a combination of suitable bioactive factors, cells, and biocompatible scaffolds offers a promising new approach for bone regeneration. To evaluate the healing capacity of platelet-rich fibrin (PRF) membranes seeded with allogeneic mesenchymal bone marrow-derived stem cells (BMSCs) on critically sized mandibular defects in a rat model. Sixty-three Sprague Dawley rats were subjected to bilateral bone defects of critical size in the mandibles created by a 5-mm diameter trephine bur. Rats were allocated to three equal groups of 21 rats each. Group I bone defects were irrigated with normal saline and designed as negative controls. Defects of group II were grafted with PRF membranes and served as positive controls, while defects of group III were grafted with PRF membranes seeded with allogeneic BMSCs. Seven rats from each group were killed at 1, 2 and 4 wk. The mandibles were dissected and prepared for routine haematoxylin and eosin (HE) staining, Masson's trichrome staining and CD68 immunohistochemical staining. Four weeks postoperatively, the percentage area of newly formed bone was significantly higher in group III (0.88 ± 0.02) than in groups I (0.02 ± 0.00) and II (0.60 ± 0.02). The amount of granulation tissue formation was lower in group III (0.12 ± 0.02) than in groups I (0.20 ± 0.02) and II (0.40 ± 0.02). The number of inflammatory cells was lower in group III (0.29 ± 0.03) than in groups I (4.82 ± 0.08) and II (3.09 ± 0.07). Bone regenerative quality of critically sized mandibular bone defects in rats was better promoted by PRF membranes seeded with BMSCs than with PRF membranes alone.

3D Printed Scaffold Combined to 2D Osteoinductive Coatings&amp;nbsp;To Repair a Critical-Size Mandibular Bone Defect

the reconstruction of large bone defects (12 cm3) remains a challenge for clinicians. We developed a new critical-size mandibular bone defect model on a mini-pig, close to human clinical issues. We analyzed the bone reconstruction obtained by a 3D printed scaffold made of clinical-grade PLA, coated with a polyelectrolyte film delivering an osteogenic bioactive molecule (BMP-2). We compared the results (CT-scan, μCT, histology) to the gold standard solution, bone autograft. We demonstrated that the dose of BMP-2 delivered from the scaffold significantly influenced the amount of regenerated bone and the repair kinetics, with a clear BMP-2 dose-dependence. Bone was homogeneously formed inside the scaffold without ectopic bone formation. The bone repair was as good as for the bone autograft. The BMP-2 doses applied in our study were reduced 20 to 75-fold compared to the commercial collagen sponges used in the current clinical applications, without any adverse effects. 3D printed PLA scaffolds loaded with reduced doses of BMP-2 can be a safe and simple solution for large bone defects faced in the clinic.

Transplantation of dedifferentiated fat cells combined with a biodegradable type I collagen-recombinant peptide scaffold for critical-size bone defects in rats.

Tissue engineering is a promising approach to supplement existing treatment strategies for craniofacial bone regeneration. In this study, a type I collagen scaffold made from a recombinant peptide (RCP) with an Arg-Gly-Asp motif was developed, and its effect on regeneration in critical-size mandibular bone defects was evaluated. Additionally, the combined effect of the scaffold and lipid-free dedifferentiated fat (DFAT) cells was assessed. Briefly, DFAT cells were separated from mature adipocytes by using a ceiling culture technique based on buoyancy. A 3 cm × 4 cm critical-size bone defect was created in the rat mandible, and regeneration was evaluated by using RCP with DFAT cells. Then, cultured DFAT cells and adipose-derived stem cells (ASCs) were seeded onto RCP scaffolds (DFAT/RCP and ASC/RCP) and implanted into the bone defects. Micro-computed tomography imaging at 8 weeks after implantation showed significantly greater bone regeneration in the DFAT/RCP group than in the ASC/RCP and RCP-alone groups. Similarly, histological analysis showed significantly greater bone width in the DFAT/RCP group than in the ASC/RCP and RCP-alone groups. These findings suggest that DFAT/RCP is effective for bone formation in critical-size bone defects and that DFAT cells are a promising source for bone regeneration.

Minor Review: An Overview of a Synthetic Nanophase Bone Substitute.

Material is reviewed that consists of reconstituted collagen fibril gel mineralized in a manner that produces biomimetically sized nanoapatites intimately associated with the fibrils. This gel is formed into usable shapes with a modulus and strength that allow it to be surgically press fitted into bony defects. The design paradigm for the material is that the nanoapatites will dissolve into soluble Ca2+ as the collagen is degraded into RGD-containing peptide fragments due to osteoclastic action. This is intended to signal to the osteoclasts to continue removing the material in a biomimetic fashion similar to bony remodeling. Preliminary experiments in a subcutaneous rat model show that the material is biocompatible with respect to inflammatory and immunogenic responses, and that it supports cellular invasion. Preliminary experiments in a critical-sized mandibular defect in rats show that the material is resorbable and functions well as a bone morphogenetic 2 (BMP-2) carrier. We have produced a range of mechanical and biological responses by varying mechanical and chemical processing of the material.

Gelfoam haemostatic agent with or without autologous bone marrow-derived stem cells for the regeneration of critical-size mandibular defects in the rabbit

This study evaluated the effect of Gelfoam sponge with and without autologous bone marrow-derived stem cells (BMSCs) on bone regeneration in critical-size mandibular defects. The study involved 56 New Zealand rabbits assigned to four groups (14 in each). The osseous defects in group I were irrigated with normal saline, those in group II were grafted with autogenous tibial bone, and those in group III were filled with Gelfoam sponge. Group IV defects were treated as for group III, but the interface between the Gelfoam sponge and bone surface was injected with BMSCs. At the end of 4weeks, seven rabbits in each group were euthanized; the remaining animals were euthanized at the end of the experiment, at 8 weeks postoperative. The percentage area of newly formed bone was significantly higher in group IV at week 4 (0.030±0.01%) and week 8 (0.060±0.03%) than in group I (0.01±0.00% and 0.02±0.00%, respectively) and group III (0.08±0.01% and 0.015±0.02%, respectively), but was lower than that in group II (0.038±0.02% and 0.082±0.01%, respectively). Thus, the combination of Gelfoam and autologous BMSCs promoted the regeneration of mandibular critical-size defects better than the use of Gelfoam alone. However, the amount of newly generated bone was lower than in defects grafted with autogenous bone.

EVALUATION OF THE OSTEOINDUCTIVE POTENTIAL OF FREEZE-DRIED HUMAN AMNIOTIC MEMBRANE (EXPERIMENTAL STUDY)

INTRODUCTION: Bone regeneration represents an important challenge in oral surgery. Several means have been employed to improve bonehealing, each having several advantages and disadvantages. The search for new materials and methods is an ongoing process.OBJECTIVES: The aim of the present study was to evaluate the bone inductive effect of the freeze-dried human amniotic membrane (FDAM)as a novel biomaterial for bone regeneration.MATERIALS AND METHODS: Twelve adult male dogs were involved in this study. Bilateral critical-sized mandibular defects were createdin each dog. One defect was left uncovered as a control. The other defect was covered with a double layered sterile freeze-dried human amnioticmembrane (FDAM) to serve as a study. At each of three time points - 4, 8, and 12 weeks - four dogs were euthanized and their mandibles wereharvested en bloc and osteotomy sites were submitted for histochemical examination to evaluate bone healing.RESULTS: The tissue samples were obtained after 4, 8, and 12 weeks for histochemical examination. The FDAM was found to enhance theblood supply to the defect area in the study group and gave rise to bone induction (P ˂0.001).CONCLUSIONS: Our study findings indicate that the FDAM has the potential for the enhancement of bone healing and bone induction.KEYWORDS: Amniotic membrane, freeze-dried, bone regeneration, critical-sized bone defect.

Erratum to "Collagen Sponge Functionalized with Chimeric Anti-BMP-2 Monoclonal Antibody Mediates Repair of Critical-Size Mandibular Continuity Defects in a Nonhuman Primate Model".

[This corrects the article DOI: 10.1155/2017/8094152.].

Three dimensionally printed bioactive ceramic scaffold osseoconduction across critical-sized mandibular defects

BackgroundVascularized bone tissue transfer, commonly used to reconstruct large mandibular defects, is challenged by long operative times, extended hospital stay, donor-site morbidity, and resulting health care. 3D-printed osseoconductive tissue-engineered scaffolds may provide an alternative solution for reconstruction of significant mandibular defects. This pilot study presents a novel 3D-printed bioactive ceramic scaffold with osseoconductive properties to treat segmental mandibular defects in a rabbit model. MethodsFull-thickness mandibulectomy defects (12 mm) were created at the mandibular body of eight adult rabbits and replaced by 3D-printed ceramic scaffold made of 100% β-tricalcium phosphate, fit to defect based on computed tomography imaging. After 8 weeks, animals were euthanized, the mandibles were retrieved, and bone regeneration was assessed. Bone growth was qualitatively assessed with histology and backscatter scanning electron microscopy, quantified both histologically and with micro computed tomography and advanced 3D image reconstruction software, and compared to unoperated mandible sections (UMSs). ResultsHistology quantified scaffold with newly formed bone area occupancy at 54.3 ± 11.7%, compared to UMS baseline bone area occupancy at 55.8 ± 4.4%, and bone area occupancy as a function of scaffold free space at 52.8 ± 13.9%. 3D volume occupancy quantified newly formed bone volume occupancy was 36.3 ± 5.9%, compared to UMS baseline bone volume occupancy at 33.4 ± 3.8%, and bone volume occupancy as a function of scaffold free space at 38.0 ± 15.4%. Conclusions3D-printed bioactive ceramic scaffolds can restore critical mandibular segmental defects to levels similar to native bone after 8 weeks in an adult rabbit, critical sized, mandibular defect model.

The synergistic effects of Sr and Si bioactive ions on osteogenesis, osteoclastogenesis and angiogenesis for osteoporotic bone regeneration.

Bioactive ions released from bioceramics play important roles for bone regeneration; however, it is unclear how each of ionic compositions in complex bioceramics exerts its specific effect on bone regeneration. The aim of present study is to elucidate the functional effects of Sr and Si ions in complex bioceramics on the regeneration of osteoporotic bone. A model bioceramic with Sr and Si-containing components (SMS) was successfully fabricated and the effects of ionic products from SMS bioceramics on the osteogenic, osteoclastic and angiogenic differentiation of rBMSCs-OVX and RANKL-induced osteoclasts were investigated. The results showed that SMS bioceramics could enhance ALP activity and expression of Col 1, OCN, Runx2 and angiogenic factors including VEGF and Ang-1. SMS bioceramics not only rebalanced the ratio of OPG/RANKL of OVX-BMSCs at early stage, but also repressed RANKL-induced osteoclast formation and expression of TRAP, DC-STAMP, V-ATPase a3, and NFATc1. The synergistic effects of Sr and Si ions were further investigated as compared with the similar concentration of Sr and Si ions alone. It was found that Sr and Si ions possessed synergistic effects on osteogenesis, osteoclastogenesis and angiogenesis, attributed to the dominant effects of Sr ions on enhancing angiogenesis and repressing osteoclastogenesis, and the dominant effects of Si ions on stimulating osteogenesis. The in vivo study using critical-size mandibular defects of OVX rat models showed that SMS bioceramics could significantly enhance bone formation and mineralization as compared with β-TCP bioceramics. It is suggested that SMS bioceramics may be a promising biomaterial for osteoporotic bone regeneration. To our knowledge, this is the first time to elucidate the specific effect of each ion from bioceramics on osteogenesis, osteoclastogenesis and angiogenesis for osteoporotic bone regeneration, paving the way to design functional biomaterials with complex compositions for tissue engineering and regenerative medicine.

Small molecule-mediated tribbles homolog 3 promotes bone formation induced by bone morphogenetic protein-2

Although bone morphogenetic protein-2 (BMP2) has demonstrated extraordinary potential in bone formation, its clinical applications require supraphysiological milligram-level doses that increase postoperative inflammation and inappropriate adipogenesis, resulting in well-documented life-threatening cervical swelling and cyst-like bone formation. Recent promising alternative biomolecular strategies are toward promoting pro-osteogenic activity of BMP2 while simultaneously suppressing its adverse effects. Here, we demonstrated that small molecular phenamil synergized osteogenesis and bone formation with BMP2 in a rat critical size mandibular defect model. Moreover, we successfully elicited the BMP2 adverse outcomes (i.e. adipogenesis and inflammation) in the mandibular defect by applying high dose BMP2. Phenamil treatment significantly improves the quality of newly formed bone by inhibiting BMP2 induced fatty cyst-like structure and inflammatory soft-tissue swelling. The observed positive phenamil effects were associated with upregulation of tribbles homolog 3 (Trib3) that suppressed adipogenic differentiation and inflammatory responses by negatively regulating PPARγ and NF-κB transcriptional activities. Thus, use of BMP2 along with phenamil stimulation or Trib3 augmentation may be a promising strategy to improve clinical efficacy and safety of current BMP therapeutics.

Three-dimensionally printed polyetherketoneketone scaffolds with mesenchymal stem cells for the reconstruction of critical-sized mandibular defects.

Additive manufacturing offers a tailored approach to tissue engineering by providing anatomically precise scaffolds onto which stem cells and growth factors can be supplied. Polyetherketoneketone (PEKK), an ideal candidate biomaterial, is limited by a poor implant-bone interface but can be functionalized with adipose-derived stem cells (ADSC) to promote integration. This in vivo study examined the interaction of a three-dimensional printed PEKK/ADSC implant within the critical-sized mandibular defect in a rabbit model. Trapezoidal porous scaffolds with dimensions of 1.5 × 1.0 × 0.5 cm were printed using selective laser sintering. ADSCs were seeded on the scaffolds that were then implanted in marginal defects created in New Zealand rabbits. Rabbits were euthanized at 10- and 20-week intervals. Microcomputed tomography was used to characterize bone ingrowth and was correlated with histological analysis. Stress testing was performed on the scaffolds before and after implantation. All scaffolds were well integrated into adjacent bone. Bone-to-tissue volume increased from 30.34% ( ± 12.46) to 61.27% ( ± 8.24), and trabecular thickness increased from 0.178 mm ( ± 0.069) to 0.331 mm ( ± 0.0306) in the 10- and 20-week groups, respectively, compared to no bone regrowth on the control side (P < 0.05). Histology confirmed integration at the bone-implant interface. Biomechanical testing revealed a compressive resistance 15 times that of bone alone (P < 0.05) CONCLUSION: 3D-printed PEKK scaffolds combined with ADSCs present a promising solution to improve the bone-implant interface and increase the resistance to forces of mastication after mandibular reconstruction. NA. Laryngoscope, 127:E392-E398, 2017.

ASSESSMENT OF BONE REGENERATION OF CRITICAL SIZE MANDIBULAR DEFECTS USING ADIPOSE DERIVED STEM CELLS: AN EXPERIMENTAL COMPARATIVE STUDY

Objectives: this study was to assess the effect of adipose derived stem cells on bone regeneration of mandibular defects of rabbits.Material and methods: Twenty four adult male New Zealand white rabbits were divided into two groups. Group A (control group) in which surgically created critical size mandibular defects were created and left to heal without grafting. Group B (test/stem group) from which adipose tissue was withdrawn and stem cells were processed and then seeded on the gel-foam scaffold to be grafted in the surgically created critical size mandibular defects. The treatment outcome was evaluated at 2, 4, 8 weeks postoperatively both radiographically and histologically. Mineralization ratio was statistically analyzed.Results: histologic and radiographic evaluation revealed significant (p ≤0.05) enhancement of bone regeneration at test group (A) as compared to control group (B). Conclusion: the use Adipose derived mesenchymal stem cells proved to be effective for enhancing bone regeneration in mandibular critical-size bone defects.