An Evaluation of Autologous Fat Injection as a Treatment for Velopharyngeal Insufficiency: A Review and Integrated Data Analysis.

BACKGROUND: Velopharyngeal insufficiency (VPI) is a condition characterized by incomplete separation of the oral and nasal cavities during speech production, thereby leading to speech abnormalities and audible nasal emissions. Subsequently, this adversely impacts communication and potentially interpersonal social interactions. Autologous fat grafting (AFG) to the velopharynx, a minimally invasive technique, aims to improve oronasal separation by providing bulk and advancing the posterior pharyngeal wall toward the soft palate. Despite its potential, the relative novelty of AFG in treating VPI has resulted in reporting of inconsistent indications, varied surgical techniques, and mixed outcomes across existing literature. METHODS: This systemic review examined the evidence of AFG for VPI treatment over the past decade (2013-2023). A thorough search across five electronic databases yielded 233 studies, with 20 meeting the inclusion criteria (e.g., utilized fat injection as their selected VPI treatment, conducted study in human subjects, did not perform additional surgical procedure at time of fat injection). Selected studies encompassed patient and surgical intervention characteristics, perceptual speech assessment (PSA) scores, gap sizes, nasalance measurements, and complications. RESULTS: The majority of patients had a prior cleft palate diagnosis (78.2%), in which nasoendoscopy was the prevalent method for visualizing the velopharyngeal port defect. Fat harvesting predominantly occurred from the abdomen (64.3%), with an average injection volume of 6.3 mL across studies. PSA and subjective gap size scores were consistently higher preoperatively than postoperatively. PSA score analysis from seven studies revealed significant and sustained improvements postoperatively. Gap size score analysis from four studies demonstrated similar preoperative and postoperative differences. Complications were reported in 17 studies, yielding a 2.7% summative complication rate among 594 cases. CONCLUSIONS: Autologous fat grafting has emerged as a minimally invasive, safe, and effective treatment for mild to moderate VPI. However, challenges remain because of variability in patient selection criteria, diagnostic modalities, and outcome measurements. This review underscores the need for randomized control trials to directly compare AFG with standard-of-care surgical interventions, providing more conclusive evidence of its clinical efficacy.

Odontogenic Cutaneous Fistula: A Zombie Diagnosis.

BACKGROUND: Odontogenic cutaneous fistula (OCF) is a pathologic communication between the cutaneous surface of the face and oral cavity. Majority of oral cutaneous fistulas are reported to arise from chronic dental infection. Delay in treatment may result in chronic tissue injury as well as cosmetic deformities. Lesions are often misdiagnosed, leading to delayed management. Misdiagnosis may be the result of the variability of clinical morphological presentation and location of lesions compounded by the lack of knowledge that these lesions can have dental etiology. It is estimated that half of patients with OCF undergo multiple dermatologic surgical operations, antibiotic regimens, and other excisions and biopsies before a correct diagnosis is made. Herein, we present a systematic review to detail cases of odontogenic cutaneous lesions that had been previously misdiagnosed or managed inappropriately. In addition, we include a case report from our own institution. The aims are to demonstrate various presentations of OCF, increase awareness of plastic surgeons and oral maxillofacial surgeons to this pathological condition, and reinforce the importance of prompt diagnosis and treatment. METHODS: The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A literature search was conducted in PubMed, Web of Science, and Cochrane databases from January 1, 2013 to July 24, 2023. The following search terms were utilized: "odontogenic cutaneous fistula" OR "odontogenic cutaneous sinus." RESULTS: Twenty-three articles published between 2013 and 2023 were included in this review. In addition, we report a case from our own institution. A total of 28 cases were included in the review. CONCLUSIONS: Diagnosis of OCF is challenging for numerous reasons. Misdiagnosis can lead to multiple trials of antibiotics and surgical procedures as well as reoccurrence of the lesion. Cases summarized highlight the importance of communication between oral maxillofacial surgery, plastic surgery, other medical subspecialists, and dentists in the evaluation of patients with head and neck lesions. Physicians should consider dental etiology in the differential diagnosis of orofacial skin lesions, even if teeth appear normal on oral examination.

Bone Tissue Engineering (BTE) of the Craniofacial Skeleton, Part II: Translational Potential of 3D-Printed Scaffolds for Defect Repair.

Computer-aided design/computer-aided manufacturing and 3-dimensional (3D) printing techniques have revolutionized the approach to bone tissue engineering for the repair of craniomaxillofacial skeletal defects. Ample research has been performed to gain a fundamental understanding of the optimal 3D-printed scaffold design and composition to facilitate appropriate bone formation and healing. Benchtop and preclinical, small animal model testing of 3D-printed bioactive ceramic scaffolds augmented with pharmacological/biological agents have yielded promising results given their potential combined osteogenic and osteoinductive capacity. However, other factors must be evaluated before newly developed constructs may be considered analogous alternatives to the "gold standard" autologous graft for defect repair. More specifically, the 3D-printed bioactive ceramic scaffold's long-term safety profile, biocompatibility, and resorption kinetics must be studied. The ultimate goal is to successfully regenerate bone that is comparable in volume, density, histologic composition, and mechanical strength to that of native bone. In vivo studies of these newly developed bone tissue engineering in translational animal models continue to make strides toward addressing regulatory and clinically relevant topics. These include the use of skeletally immature animal models to address the challenges posed by craniomaxillofacial defect repair in pediatric patients. This manuscript reviews the most recent preclinical animal studies seeking to assess 3D-printed ceramic scaffolds for improved repair of critical-sized craniofacial bony defects.

Nasopharyngoscopic Evaluation of Velopharyngeal Closure During Speech.

Definitive oronasal separation through closure of the velopharyngeal (VP) sphincter is necessary for the development of normal speech and feeding. Individuals with velopharyngeal incompetence or insufficiency often exhibit hypernasal speech, poor speech intelligibility, and nasal regurgitation. Assessment of VP sphincter function using nasopharyngoscopy is a key element in identifying VP dysfunction. A foundational understanding of normal anatomy and physiology of the velopharyngeal mechanism is paramount to successful diagnosis. This includes recognition of 4 distinct VP sphincter closure patterns: coronal, sagittal, circular, and circular with Passavant's ridge. In this study, the authors showcase 2 patients with velopharyngeal competence who presented to an ear, nose, and throat clinic for nasopharyngoscopic evaluation. This study sought to demonstrate the use of nasopharyngoscopy to recognize velopharyngeal closure patterns and discuss how they may influence the surgical management of VP dysfunction.

Evaluation of Porcine-Derived Collagen Membranes for Soft Tissue Augmentation in the Oral Cavity: An In Vivo Study.

The use of porcine-derived collagen membranes (PDCM) to improve intraoral soft tissue rehabilitation remains under investigation. Different degrees of crosslinking have yielded differences in resorption time and inflammation surrounding collagen membranes. The aim of this study was to evaluate the in vivo performance of bilayered PDCMs with varying degrees of crosslinking for the regeneration of oral soft tissue defects. Bilateral split-thickness oral mucosa defects were created in mandibles of beagles (n=17) and assigned to one of the following: bilayer PDCM (high crosslinking porcine dermis in sheet form-H-xlink) and (low crosslinking porcine dermis in sheet form-L-xlink), bilayer PDCM (non-crosslinked predicate collagen membrane in spongy form-Ctrl), or negative control (Sham) and compared with positive control (unoperated). Animals were euthanized after 4-, 8-, or 12-weeks of healing to evaluate soft tissue regeneration and remodeling through histomorphometric analyses. H-xlink membranes presented delayed healing with a poorly developed epithelial layer (analogous to the sham group) across time points. Relative to Ctrl at 8 and 12 weeks, defects treated with H-xlink presented no difference in semiquantitative scores ( P > 0.05), while L-xlink exhibited greater healing ( P = 0.042, P = 0.043, at 8 and 12 weeks, respectively). Relative to positive control, L-xlink exhibited similar healing at 8 weeks and greater healing at 12 weeks ( P = 0.037) with a well-developed epithelial layer. Overall, groups treated with L-xlink presented with greater healing relative to the positive control after 12 weeks of healing and may serve as an alternative to autologous grafts for intraoral soft tissue regeneration.

Application of 3D Printing in Cleft Lip and Palate Repair.

This manuscript reviews the transformative impact of 3-dimensional (3D) printing technologies in the treatment and management of cleft lip and palate (CLP), highlighting its application across presurgical planning, surgical training, implantable scaffolds, and postoperative care. By integrating patient-specific data through computer-aided design and manufacturing, 3D printing offers tailored solutions that improve surgical outcomes, reduce operation times, and enhance patient care. The review synthesizes current research findings, technical advancements, and clinical applications, illustrating the potential of 3D printing to revolutionize CLP treatment. Further, it discusses the future directions of combining 3D printing with other innovative technologies like artificial intelligence, 4D printing, and in situ bioprinting for more comprehensive care strategies. This paper underscores the necessity for multidisciplinary collaboration and further research to overcome existing challenges and fully utilize the capabilities of 3D printing in CLP repair.

Translational Experimental Basis of Indirect Adenosine Receptor Agonist Stimulation for Bone Regeneration: A Review.

Bone regeneration remains a significant clinical challenge, often necessitating surgical approaches when healing bone defects and fracture nonunions. Within this context, the modulation of adenosine signaling pathways has emerged as a promising therapeutic option, encouraging osteoblast activation and tempering osteoclast differentiation. A literature review of the PubMed database with relevant keywords was conducted. The search criteria involved in vitro or in vivo models, with clear methodological descriptions. Only studies that included the use of indirect adenosine agonists, looking at the effects of bone regeneration, were considered relevant according to the eligibility criteria. A total of 29 articles were identified which met the inclusion and exclusion criteria, and they were reviewed to highlight the preclinical translation of adenosine agonists. While preclinical studies demonstrate the therapeutic potential of adenosine signaling in bone regeneration, its clinical application remains unrealized, underscoring the need for further clinical trials. To date, only large, preclinical animal models using indirect adenosine agonists have been successful in stimulating bone regeneration. The adenosine receptors (A1, A2A, A2B, and A3) stimulate various pathways, inducing different cellular responses. Specifically, indirect adenosine agonists act to increase the extracellular concentration of adenosine, subsequently agonizing the respective adenosine receptors. The agonism of each receptor is dependent on its expression on the cell surface, the extracellular concentration of adenosine, and its affinity for adenosine. This comprehensive review analyzed the multitude of indirect agonists currently being studied preclinically for bone regeneration, discussing the mechanisms of each agonist, their cellular responses in vitro, and their effects on bone formation in vivo.

Ultrathin lithium disilicate and translucent zirconia crowns for posterior teeth: Survival and failure modes.

PURPOSE: To evaluate the reliability and failure modes of ultrathin (0.5 mm) lithium disilicate, translucent and ultra-translucent zirconia crowns for posterior teeth restorations. MATERIALS AND METHODS: Fifty-four mandibular first molar crowns of three ceramic materials: (1) Lithium disilicate (e.max CAD, Ivoclar Vivadent), (2) 3Y-TZP (Zirconn Translucent, Vipi), and (3) 5Y-PSZ (Cercon XT, Dentsply Sirona), with 0.5 mm of thickness were milled and cemented onto composite resin abutments. Eighteen samples of each group were tested under mouth-motion step-stress accelerated life testing in a humid environment using mild, moderate, and aggressive profiles. Data was subjected to Weibull statistics. Use level curves were plotted and reliability was calculated for a given mission of 100,000 cycles at 100, 200, and 300 N. Fractographic analyses of representative samples were performed in scanning electron microscope. RESULTS: Beta (ß) values suggest that failures were dictated by material's strength for lithium disilicate and by fatigue damage accumulation for both zirconias. No significant differences were detected in Weibull modulus and characteristic strength among groups. At a given mission of 100,000 cycles at 100 N, lithium disilicate presented higher reliability (98% CB: 95-99) regarding 3Y-TZP and 5Y-PSZ groups (84% CB: 65%-93% and 79% CB: 37&-94%, respectively). At 200 N, lithium disilicate reliability (82% CB: 66%-91%) was higher than 5Y-PSZ (20% CB: 4%-44%) and not significantly different from 3Y-TZP (54% CB: 32%-72%). Furthermore, at 300 N no significant differences in reliability were detected among groups, with a notable reduction in the reliability of all materials. Fractographic analyses showed that crack initiated at the interface between the composite core and the ceramic crowns due to tensile stress generated at the intaglio surface. CONCLUSIONS: Ultrathin lithium disilicate crowns demonstrated higher reliability relative to zirconia crowns at functional loads. Lithium disilicate and zirconia crown's reliability decreased significantly for missions at higher loads and similar failure modes were observed regardless of crown material. The indication of 0.5 mm thickness crowns in high-load bearing regions must be carefully evaluated. CLINICAL SIGNIFICANCE: Ultraconservative lithium disilicate and zirconia crowns of 0.5 mm thickness may be indicated in anterior restorations and pre-molars. Their clinical indication in high-load requirement regions must be carefully evaluated.

The Aesthetic Surgery Education and Research Foundation (ASERF): A 30-Year Retrospective Analysis.

Federal government research grants provide limited funding to plastic surgeon-scientists, with reconstructive research taking precedence over aesthetic research. The Aesthetic Surgery Education and Research Foundation (ASERF) is a nonprofit, 501(c)(3) organization that seeks to support innovative, diverse research endeavors within aesthetic surgery. A total of 130 ASERF-funded studies and 32 non-funded applications from 1992 to 2022 were reviewed. Kruskal Wallis, Fisher's exact, and chi-squared tests were utilized to assess the potential relationship between self-identified gender, practice setting, geographical location, and study type with individual grant amounts and grant funding decision. Although significant differences were observed between male and female grant recipient h-indices (P < .05), there were no differences in the amount of funding they received (P > .05). Grant amounts were also consistent between study types as well as principal investigator practice settings and geographical locations (P > .05). The subanalysis revealed that the practice setting of the primary investigator (PI) was the only variable to exhibit a significant association with the decision to award funding (P < .05). Further, of the 61 applicants between 2017 and 2022, only 2 PIs self-identified as female. ASERF serves as an excellent funding source for global aesthetic surgery. To promote further research diversification, increased emphasis should be placed on recruiting applicants from outside academia and those who identify as female or gender nonbinary.

Bone Tissue Engineering (BTE) of the Craniofacial Skeleton, Part I: Evolution and Optimization of 3D-Printed Scaffolds for Repair of Defects.

Bone tissue regeneration is a complex process that proceeds along the well-established wound healing pathway of hemostasis, inflammation, proliferation, and remodeling. Recently, tissue engineering efforts have focused on the application of biological and technological principles for the development of soft and hard tissue substitutes. Aim is directed towards boosting pathways of the healing process to restore form and function of tissue deficits. Continued development of synthetic scaffolds, cell therapies, and signaling biomolecules seeks to minimize the need for autografting. Despite being the current gold standard treatment, it is limited by donor sites' size and shape, as well as donor site morbidity. Since the advent of computer-aided design/computer-aided manufacturing (CAD/CAM) and additive manufacturing (AM) techniques (3D printing), bioengineering has expanded markedly while continuing to present innovative approaches to oral and craniofacial skeletal reconstruction. Prime examples include customizable, high-strength, load bearing, bioactive ceramic scaffolds. Porous macro- and micro-architecture along with the surface topography of 3D printed scaffolds favors osteoconduction and vascular in-growth, as well as the incorporation of stem and/or other osteoprogenitor cells and growth factors. This includes platelet concentrates (PCs), bone morphogenetic proteins (BMPs), and some pharmacological agents, such as dipyridamole (DIPY), an adenosine A 2A receptor indirect agonist that enhances osteogenic and osteoinductive capacity, thus improving bone formation. This two-part review commences by presenting current biological and engineering principles of bone regeneration utilized to produce 3D-printed ceramic scaffolds with the goal to create a viable alternative to autografts for craniofacial skeleton reconstruction. Part II comprehensively examines recent preclinical data to elucidate the potential clinical translation of such 3D-printed ceramic scaffolds.

In vitro assessment of the effect of luting agents, abutment height, and fatigue on the retention of zirconia crowns luted to titanium base implant abutments.

STATEMENT OF PROBLEM: The bonding of implant-supported prostheses is determined by abutment material, convergence angle, height, surface treatment, and luting agents. However, studies evaluating the bonding of luting agents to titanium base abutments with different heights under fatigue conditions are scarce. PURPOSE: The purpose of this in vitro study was to evaluate the retention of zirconia crowns bonded with different luting agents to titanium base abutments of different heights before and after fatigue testing. MATERIAL AND METHODS: Zirconia crowns were designed, milled, and distributed into 4 experimental groups according to the luting agents (G-Multi Primer/G-Cem LinkForce [MP/GC] and Scotchbond Universal/RelyX Ultimate [SU/RU]) and titanium base abutment heights (2.5 mm and 4 mm) (n=10). Pull-out testing was performed in a universal testing machine at a crosshead speed of 1 mm/min until crown displacement. Fatigue testing was performed by an electric precision fatigue simulator (1×106 cycles; 100 N; and 15 Hz), followed by pull-out testing of fatigued specimens. Collected data were statistically evaluated by using a linear mixed model after post hoc comparisons by the least significant difference test (α=.05). RESULTS: Luting agents, abutment heights, and fatigue influenced the bonding retention of zirconia crowns to titanium base abutments. SU/RU agents promoted higher pull-out compared with MP/GC for both abutment heights before and after fatigue. Higher abutment height increased pull-out regarding lower abutment height for SU/RU materials before and after fatigue testing. Although fatigue had no significant effect on the pull-out of MP/GC, lower bond retention was observed for SU/RU after fatigue, regardless of abutment height. CONCLUSIONS: Luting agent composition and the interaction with abutment height and fatigue influenced the retention of zirconia crowns to titanium base abutments.

Locally Secreted Semaphorin 4D Is Engaged in Both Pathogenic Bone Resorption and Retarded Bone Regeneration in a Ligature-Induced Mouse Model of Periodontitis.

It is well known that Semaphorin 4D (Sema4D) inhibits IGF-1-mediated osteogenesis by binding with PlexinB1 expressed on osteoblasts. However, its elevated level in the gingival crevice fluid of periodontitis patients and the broader scope of its activities in the context of potential upregulation of osteoclast-mediated periodontal bone-resorption suggest the need for further investigation of this multifaceted molecule. In short, the pathophysiological role of Sema4D in periodontitis requires further study. Accordingly, attachment of the ligature to the maxillary molar of mice for 7 days induced alveolar bone-resorption accompanied by locally elevated, soluble Sema4D (sSema4D), TNF-α and RANKL. Removal of the ligature induced spontaneous bone regeneration during the following 14 days, which was significantly promoted by anti-Sema4D-mAb administration. Anti-Sema4D-mAb was also suppressed in vitro osteoclastogenesis and pit formation by RANKL-stimulated BMMCs. While anti-Sema4D-mAb downmodulated the bone-resorption induced in mouse periodontitis, it neither affected local production of TNF-α and RANKL nor systemic skeletal bone remodeling. RANKL-induced osteoclastogenesis and resorptive activity were also suppressed by blocking of CD72, but not Plexin B2, suggesting that sSema4D released by osteoclasts promotes osteoclastogenesis via ligation to CD72 receptor. Overall, our data indicated that ssSema4D released by osteoclasts may play a dual function by decreasing bone formation, while upregulating bone-resorption.

A Histologic and Histomorphometric Evaluation of an Allograft, Xenograft, and Alloplast Graft for Alveolar Ridge Preservation in Humans: A Randomized Controlled Clinical Trial.

The aim of this study was to clinically evaluate the guided bone regeneration (GBR) potential of allograft, xenograft, and alloplastic materials in combination with resorbable membranes in extraction sockets. The qualitative and quantitative assessments of this prospective study were accomplished through histologic and histomorphometric analysis. Three experimental groups and 1 control group for comparison (n = 8) received either an allograft (human cancellous bone, freeze dried, Deutsches Institut für Zell und Gewebeersatz, Berlin, Germany), xenograft (BioOss, Geistlich Pharma AG, Wolhusen, Switzerland), or alloplast (biphasic calcium sulphate, Bondbone, MIS Implants Technologies Ltd., Charlotte, NC). The negative control group received no regenerative material. Tissue samples were then qualitatively and quantitatively evaluated as a function of percentage of new vital bone, graft particles content, soft tissue, and bone marrow over time. All 3 study groups presented bone volume suitable for the successful placement of a dental implant. The xenograft group yielded significantly less amount of vital bone compared with the allograft and alloplast groups. When comparing the percentage of residual graft particles, there was significantly greater amounts associated with the xenograft group in contrast to the allograft and alloplast groups. Similarly, a significantly increased amount of soft tissue percentage was observed within the xenograft group relative to all other groups. No significant differences were observed in the percentage of residual graft particles between the allograft and alloplast groups. There were also no significant differences detected in vital bone percentage between the allograft, alloplast, and control groups. When evaluating the bone marrow percentage, the only significant difference detected was between the xenograft and alloplast materials. Overall, no complications (ie, fever, malaise, purulence or fistula) were observed during the entirety of clinical trial among all patients. The greatest GBR potential was associated with the allograft material because of the greater degree of vital bone and the lowest percentage of residual graft particles. All studied bone substitute materials resulted in bone apposition for efficient use in alveolar ridge preservation procedures.

Effect of Surgical Instrumentation Variables on the Osseointegration of Narrow- and Wide-Diameter Short Implants.

PURPOSE: The aim of the present study was to systematically analyze how a multifactorial surgical instrumentation approach affects osseointegration on both narrow-diameter and wide-diameter short implants. MATERIALS AND METHODS: Twelve skeletally mature female sheep were used in the study along with 144 plateau-root-form healing chamber titanium (Ti-6Al-4V) implants (Bicon LLC, Boston, MA), evenly distributed between narrow (3.5 mm) and wide (6.0 mm) diameters. The presence or the absence of irrigation, different drilling speeds, and 2 time points quantifying bone-implant contact (BIC) and bone area fraction occupancy (BAFO) to evaluate the osteogenic parameters around the implants. RESULTS: There were no signs of inflammation, infection, or failure of the implants observed at either healing period. The narrow 3.5-mm implant, at 6 weeks, yielded significant differences in terms of BIC at a drilling speed of 50 rotations per minute (RPM), with higher values of the samples using irrigation (30.6 ± 6.1%) compared with those without (19.7 ± 6.1%). No statistical differences were detected for 500 and 1,000 RPM with or without irrigation. The wide 6-mm diameter implant showed differences with respect to drilling speed, 500 and 1,000 RPM, with higher values associated with samples subjected to irrigation. BAFO results, for both diameters, only detected statistical differences between the 2 times (3 vs 6 weeks); no statistical differences were detected when evaluating as a function of time, drilling speed, and irrigation. CONCLUSIONS: Surgical instrumentation variables (ie, drilling speed [RPM] and irrigation) yielded to be more of an effect for BIC at longer healing time (6 weeks) for the wider implants. Furthermore, deploying narrow or wide plateau-root-form implants, where conditions allow, has shown to be a safe alternative, considering the high BIC and BAFO values observed, independent of irrigation.

Transforming the Degradation Rate of ß-tricalcium Phosphate Bone Replacement Using 3-Dimensional Printing.

BACKGROUND: ß-Tricalcium phosphate (ß-TCP) is one of the most common synthetic bone grafting materials utilized in craniofacial reconstruction; however, it is limited by a slow degradation rate. The aim of this study was to leverage 3-dimensional (3D) printing in an effort to accelerate the degradation kinetics of ß-TCP. METHODS: Twenty-two 1-month-old New Zealand white rabbits underwent creation of calvarial and alveolar defects, repaired with 3D-printed ß-TCP scaffolds coated with 1000 µM of osteogenic agent dipyridamole. Rabbits were euthanized after 2, 6, and 18 months after surgical intervention. Bone regeneration, scaffold degradation, and bone mechanical properties were quantified. RESULTS: Histological analysis confirmed the generation of vascularized and organized bone. Microcomputed tomography analysis from 2 to 18 months demonstrated decreased scaffold volume within calvarial (23.6% ± 2.5%, 5.1% ± 2.2%; P < 0.001) and alveolar (21.5% ± 2.2%, 0.2% ± 1.9%; P < 0.001) defects, with degradation rates of 54.6%/year and 90.5%/year, respectively. Scaffold-inducted bone generation within the defect was volumetrically similar to native bone in the calvarium (55.7% ± 6.9% vs 46.7% ± 6.8%; P = 0.064) and alveolus (31.4% ± 7.1% vs 33.8% ± 3.7%; P = 0.337). Mechanical properties between regenerated and native bone were similar. CONCLUSIONS: Our study demonstrates an improved degradation profile and replacement of absorbed ß-TCP with vascularized, organized bone through 3D printing and addition of an osteogenic agent. This novel additive manufacturing and tissue engineering protocol has implications to the future of craniofacial skeletal reconstruction as a safe and efficacious bone tissue engineering method.

Histomorphometric analysis of implant osseointegration using hydrophilic implants in diabetic rats.

OBJECTIVES: To evaluate peri-implant bone formation of titanium implants using an in vivo rat model with and without uncontrolled diabetes mellitus (DM) to evaluate osseointegration of hydrophobic (Neoporos®) and hydrophilic (Acqua®) surfaces. MATERIALS AND METHODS: 54 rats were divided into two groups: DM group (DMG) (streptozotocin-induced diabetes) and a control group (CG). Implants with hydrophobic (Neoporos®) and hydrophilic surfaces (Acqua®) were placed in the left or right tibia of animals. Animals were further divided into three groups (n = 9) euthanized after 7, 14, or 28 days. Bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) were assessed in total, cortical, and medullary areas. RESULTS: The DMG group, after a 7-day healing period, yielded with the Acqua implants presented significantly higher total BIC (+37.9%; p=0.03) and trabecular BIC (%) (+46.3%; p=0.02) values in comparison to the Neoporos implants. After 28 days of healing, the CG yielded that the cortical BAFO of Acqua implants to be significantly, 14%, higher (p=0.04) than Neoporos implants. CONCLUSION: The positive effects of the Acqua surface were able to counteract the adverse impact of uncontrolled DM at early osseointegration periods. After 28 days in vivo, the metabolic systemic impairment caused by DM overcame the surface treatment effect, leading to impaired osseointegration in both hydrophilic and hydrophobic implants. CLINICAL RELEVANCE: The adverse effects of diabetes mellitus with respect to bone healing may be minimized by deploying implants with strategically modified surfaces. This study evaluated the effects of implants with Acqua® and Neoporos® surfaces in both diabetic and healthy animals. During the initial healing period in diabetic animals, the hydrophilic surface was demonstrated to have beneficial effect on osseointegration in comparison to the hydrophobic surface. The results provide an insight into early healing, but the authors suggest that a future short-term and long-term clinical study is needed to assess the possible benefit of the Acqua® implant as well as in increasing the predictability of implant osseointegration.

Three-Dimensionally-Printed Bioactive Ceramic Scaffolds: Construct Effects on Bone Regeneration.

BACKGROUND/PURPOSE: The utilization of three-dimensionally (3D)-printed bioceramic scaffolds composed of beta-tricalcium phosphate in conjunction with dipyridamole have shown to be effective in the osteogenesis of critical bone defects in both skeletally immature and mature animals. Furthermore, previous studies have proven the dura and pericranium's osteogenic capacity in the presence of 3D-printed scaffolds; however, the effect galea aponeurotica on osteogenesis in the presence of 3D scaffolds remains unclear. METHOD/DESCRIPTION: Critical-sized (11 mm) bilateral calvarial defects were created in 35-day old rabbits (n = 7). Two different 3D scaffolds were created, with one side of the calvaria being treated with a solid nonporous cap and the other with a fully porous cap. The solid cap feature was designed with the intention of preventing communication of the galea and the ossification site, while the porous cap permitted such communication. The rabbits were euthanized 8 weeks postoperatively. Calvaria were analyzed using microcomputed tomography, 3D reconstruction, and nondecalcified histologic sectioning in order assess differences in bone growth between the two types of scaffolding. RESULTS: Scaffolds with the solid (nonporous) cap yielded greater percent bone volume (P = 0.012) as well as a greater percent potential bone (P = 0.001) compared with the scaffolds with a porous cap. The scaffolds with porous caps also exhibited a greater percent volume of soft tissue (P < 0.001) presence. There were no statistically significant differences detected in scaffold volume. CONCLUSION: A physical barrier preventing the interaction of the galea aponeurotica with the scaffold leads to significantly increased calvarial bone regeneration in comparison with the scaffolds allowing for this interaction. The galea's interaction also leads to more soft tissue growth hindering the in growth of bone in the porous-cap scaffolds.

Parenchymal and stromal tissue regeneration of tooth organ by pivotal signals reinstated in decellularized matrix.

Cells are transplanted to regenerate an organs' parenchyma, but how transplanted parenchymal cells induce stromal regeneration is elusive. Despite the common use of a decellularized matrix, little is known as to the pivotal signals that must be restored for tissue or organ regeneration. We report that Alx3, a developmentally important gene, orchestrated adult parenchymal and stromal regeneration by directly transactivating Wnt3a and vascular endothelial growth factor. In contrast to the modest parenchyma formed by native adult progenitors, Alx3-restored cells in decellularized scaffolds not only produced vascularized stroma that involved vascular endothelial growth factor signalling, but also parenchymal dentin via the Wnt/ß-catenin pathway. In an orthotopic large-animal model following parenchyma and stroma ablation, Wnt3a-recruited endogenous cells regenerated neurovascular stroma and differentiated into parenchymal odontoblast-like cells that extended the processes into newly formed dentin with a structure-mechanical equivalency to native dentin. Thus, the Alx3-Wnt3a axis enables postnatal progenitors with a modest innate regenerative capacity to regenerate adult tissues. Depleted signals in the decellularized matrix may be reinstated by a developmentally pivotal gene or corresponding protein.

Biomaterial and biomechanical considerations to prevent risks in implant therapy.

This paper is aimed to present a biomaterials perspective in implant therapy that fosters improved bone response and long-term biomechanical competence from surgical instrumentation to final prosthetic rehabilitation. Strategies to develop implant surface texturing will be presented and their role as an ad hoc treatment discussed in light of the interplay between surgical instrumentation and implant macrogeometric configuration. Evidence from human retrieved implants in service for several years and from in vivo studies will be used to show how the interplay between surgical instrumentation and implant macrogeometry design affect osseointegration healing pathways, and bone morphologic and long-term mechanical properties. Also, the planning of implant-supported prosthetic rehabilitations targeted at long-term performance will be appraised from a standpoint where personal preferences (eg, cementing or screwing a prosthesis) can very often fail to deliver the best patient care. Lastly, the acknowledgement that every rehabilitation will have its strength degraded over time once in function will be highlighted, since the potential occurrence of even minor failures is rarely presented to patients prior to treatment.

FOXO1 regulates VEGFA expression and promotes angiogenesis in healing wounds.

Angiogenesis is a critical aspect of wound healing. We investigated the role of keratinocytes in promoting angiogenesis in mice with lineage-specific deletion of the transcription factor FOXO1. The results indicate that keratinocyte-specific deletion of Foxo1 reduces VEGFA expression in mucosal and skin wounds and leads to reduced endothelial cell proliferation, reduced angiogenesis, and impaired re-epithelialization and granulation tissue formation. In vitro FOXO1 was needed for VEGFA transcription and expression. In a porcine dermal wound-healing model that closely resembles healing in humans, local application of a FOXO1 inhibitor reduced angiogenesis. This is the first report that FOXO1 directly regulates VEGFA expression and that FOXO1 is needed for normal angiogenesis during wound healing. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.