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.

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.

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.

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.

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.

What a Ratchet! A Gripping Case Report of an Entrapped Finger with an Unyielding Wrench.

Finger entrapment with rings or ring-like objects is an uncommon possible hand emergency. In cases in which noncutting removal is ineffective, ring cutters or dental drills with carbide or diamond burs have been successfully used. However, objects composed of hard metallic alloys, such as lug nuts or wrenches, are often resistant to such equipment. In these instances, larger diameter metal cutting burrs or rasps may be more advantageous. Due to their increased size and cutting power, these tools are better suited to handle the toughness of hard metals. In this case report, we present the effective and efficient removal of a stainless steel wrench from an entrapped digit using a helicoidal rasp. Availability of this instrument within orthopedic departments may prevent the delays often described in the treatment of finger entrapment when traditional cutting equipment fails.

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.

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 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.

3D Printing Applications for Craniomaxillofacial Reconstruction: A Sweeping Review.

The field of craniomaxillofacial (CMF) surgery is rich in pathological diversity and broad in the ages that it treats. Moreover, the CMF skeleton is a complex confluence of sensory organs and hard and soft tissue with load-bearing demands that can change within millimeters. Computer-aided design (CAD) and additive manufacturing (AM) create extraordinary opportunities to repair the infinite array of craniomaxillofacial defects that exist because of the aforementioned circumstances. 3D printed scaffolds have the potential to serve as a comparable if not superior alternative to the "gold standard" autologous graft. In vitro and in vivo studies continue to investigate the optimal 3D printed scaffold design and composition to foster bone regeneration that is suited to the unique biological and mechanical environment of each CMF defect. Furthermore, 3D printed fixation devices serve as a patient-specific alternative to those that are available off-the-shelf with an opportunity to reduce operative time and optimize fit. Similar benefits have been found to apply to 3D printed anatomical models and surgical guides for preoperative or intraoperative use. Creation and implementation of these devices requires extensive preclinical and clinical research, novel manufacturing capabilities, and strict regulatory oversight. Researchers, manufacturers, CMF surgeons, and the United States Food and Drug Administration (FDA) are working in tandem to further the development of such technology within their respective domains, all with a mutual goal to deliver safe, effective, cost-efficient, and patient-specific CMF care. This manuscript reviews FDA regulatory status, 3D printing techniques, biomaterials, and sterilization procedures suitable for 3D printed devices of the craniomaxillofacial skeleton. It also seeks to discuss recent clinical applications, economic feasibility, and future directions of this novel technology. By reviewing the current state of 3D printing in CMF surgery, we hope to gain a better understanding of its impact and in turn identify opportunities to further the development of patient-specific surgical care.

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.

Osteogenic differentiation and reconstruction of mandible defects using a novel resorbable membrane: An in vitro and in vivo experimental study.

To evaluate the cellular response of both an intact fish skin membrane and a porcine-derived collagen membrane and investigate the bone healing response of these membranes using a translational, preclinical, guided-bone regeneration (GBR) canine model. Two different naturally sourced membranes were evaluated in this study: (i) an intact fish skin membrane (Kerecis Oral®, Kerecis) and (ii) a porcine derived collagen (Mucograft®, Geistlich) membrane, positive control. For the in vitro experiments, human osteoprogenitor (hOP) cells were used to assess the cellular viability and proliferation at 24, 48, 72, and 168 h. ALPL, COL1A1, BMP2, and RUNX2 expression levels were analyzed by real-time PCR at 7 and 14 days. The preclinical component was designed to mimic a GBR model in canines (n = 12). The first step was the extraction of premolars (P1-P4) and the 1st molars bilaterally, thereby creating four three-wall box type defects per mandible (two per side). Each defect site was filled with bone grafting material, which was then covered with one of the two membranes (Kerecis Oral® or Mucograft®). The groups were nested within the mandibles of each subject and membranes randomly allocated among the defects to minimize potential site bias. Samples were harvested at 30-, 60-, and 90-days and subjected to computerized microtomography (µCT) for three-dimensional reconstruction to quantify bone formation and graft degradation, in addition to histological processing to qualitatively analyze bone regeneration. Neither the intact fish skin membrane nor porcine-based collagen membrane presented cytotoxic effects. An increase in cell proliferation rate was observed for both membranes, with the Kerecis Oral® outperforming the Mucograft® at the 48- and 168-hour time points. Kerecis Oral® yielded higher ALPL expression relative to Mucograft® at both 7- and 14-day points. Additionally, higher COL1A1 expression was observed for the Kerecis Oral® membrane after 7 days but no differences were detected at 14 days. The membranes yielded similar BMP2 and RUNX2 expression at 7 and 14 days. Volumetric reconstructions and histologic micrographs indicated gradual bone ingrowth along with the presence of particulate bone grafts bridging the defect walls for both Kerecis Oral® and Mucograft® membranes, which allowed for the reestablishment of the mandible shape after 90 days. New bone formation significantly increased from 30 to 60 days, and from 60 to 90 days in vivo, without significant differences between membranes. The amount of bovine grafting material (%) within the defects significantly decreased from 30 to 90 days. Collagen membranes led to an upregulation of cellular proliferation and adhesion along with increased expression of genes associated with bone healing, particularly the intact fish skin membrane. Despite an increase in the bone formation rate in the defect over time, there was no significant difference between the membranes.

Employing Indirect Adenosine 2A Receptors (A2AR) to Enhance Osseointegration of Titanium Devices: A Pre-Clinical Study.

The present study aimed to evaluate the effect of dipyridamole, an indirect adenosine 2A receptors (A2AR), on the osseointegration of titanium implants in a large, translational pre-clinical model. Sixty tapered, acid-etched titanium implants, treated with four different coatings ((i) Type I Bovine Collagen (control), (ii) 10 µM dipyridamole (DIPY), (iii) 100 µM DIPY, and (iv) 1000 µM DIPY), were inserted in the vertebral bodies of 15 female sheep (weight ~65 kg). Qualitative and quantitative analysis were performed after 3, 6, and 12 weeks in vivo to assess histological features, and percentages of bone-to-implant contact (%BIC) and bone area fraction occupancy (%BAFO). Data was analyzed using a general linear mixed model analysis with time in vivo and coating as fixed factors. Histomorphometric analysis after 3 weeks in vivo revealed higher BIC for DIPY coated implant groups (10 µM (30.42% ± 10.62), 100 µM (36.41% ± 10.62), and 1000 µM (32.46% ± 10.62)) in comparison to the control group (17.99% ± 5.82). Further, significantly higher BAFO was observed for implants augmented with 1000 µM of DIPY (43.84% ± 9.97) compared to the control group (31.89% ± 5.46). At 6 and 12 weeks, no significant differences were observed among groups. Histological analysis evidenced similar osseointegration features and an intramembranous-type healing pattern for all groups. Qualitative observation corroborated the increased presence of woven bone formation in intimate contact with the surface of the implant and within the threads at 3 weeks with increased concentrations of DIPY. Coating the implant surface with dipyridamole yielded a favorable effect with regard to BIC and BAFO at 3 weeks in vivo. These findings suggest a positive effect of DIPY on the early stages of osseointegration.

Evaluation of instrumentation and pedicle screw design for posterior lumbar fixation: A pre-clinical in vivo/ex vivo ovine model.

Background: Stabilization procedures of the lumbar spine are routinely performed for various conditions, such as spondylolisthesis and scoliosis. Spine surgery has become even more common, with the incidence rates increasing ~30% between 2004 and 2015. Various solutions to increase the success of lumbar stabilization procedures have been proposed, ranging from the device's geometrical configuration to bone quality enhancement via grafting and, recently, through modified drilling instrumentation. Conventional (manual) instrumentation renders the excavated bony fragments ineffective, whereas the "additive" osseodensification rotary drilling compacts the bone fragments into the osteotomy walls, creating nucleating sites for regeneration. Methods: This study aimed to compare both manual versus rotary Osseodensification (OD) instrumentation as well as two different pedicle screw thread designs in a controlled split animal model in posterior lumbar stabilization to determine the feasibility and potential advantages of each variable with respect to mechanical stability and histomorphology. A total of 164 single thread (82 per thread configuration), pedicle screws (4.5 × 35 mm) were used for the study. Each animal received eight pedicles (four per thread design) screws, which were placed in the lumbar spine of 21 adult sheep. One side of the lumbar spine underwent rotary osseodensification instrumentation, while the contralateral underwent conventional, hand, instrumentation. The animals were euthanized after 6- and 24-weeks of healing, and the vertebrae were removed for biomechanical and histomorphometric analyses. Pullout strength and histologic analysis were performed on all harvested samples. Results: The rotary instrumentation yielded statistically (p = 0.026) greater pullout strength (1060.6 N ± 181) relative to hand instrumentation (769.3 N ± 181) at the 24-week healing time point. Histomorphometric analysis exhibited significantly higher degrees of bone to implant contact for the rotary instrumentation only at the early healing time point (6 weeks), whereas bone area fraction occupancy was statistically higher for rotary instrumentation at both healing times. The levels of soft tissue infiltration were lower for pedicle screws placed in osteotomies prepared using OD instrumentation relative to hand instrumentation, independent of healing time. Conclusion: The rotary instrumentation yielded enhanced mechanical and histologic results relative to the conventional hand instrumentation in this lumbar spine stabilization model.

Engineering 3D Printed Bioceramic Scaffolds to Reconstruct Critical-Sized Calvaria Defects in a Skeletally Immature Pig Model.

BACKGROUND: Three-dimensional printed bioceramic scaffolds composed of 100% ß-tricalcium phosphate augmented with dipyridamole (3DPBC-DIPY) can regenerate bone across critically sized defects in skeletally mature and immature animal models. Before human application, safe and effective bone formation should be demonstrated in a large translational animal model. This study evaluated the ability of 3DPBC-DIPY scaffolds to restore critically sized calvarial defects in a skeletally immature, growing minipig. METHODS: Unilateral calvarial defects (~1.4 cm) were created in 6-week-old Göttingen minipigs ( n = 12). Four defects were filled with a 1000 µm 3DPBC-DIPY scaffold with a cap (a solid barrier on the ectocortical side of the scaffold to prevent soft-tissue infiltration), four defects were filled with a 1000 µm 3DPBC-DIPY scaffold without a cap, and four defects served as negative controls (no scaffold). Animals were euthanized 12 weeks postoperatively. Calvariae were subjected to micro-computed tomography, 3D reconstruction with volumetric analysis, qualitative histologic analysis, and nanoindentation. RESULTS: Scaffold-induced bone growth was statistically greater than in negative controls ( P ≤ 0.001), and the scaffolds with caps produced significantly more bone generation compared with the scaffolds without caps ( P ≤ 0.001). Histologic analysis revealed woven and lamellar bone with haversian canals throughout the regenerated bone. Cranial sutures were observed to be patent, and there was no evidence of ectopic bone formation or excess inflammatory response. Reduced elastic modulus and hardness of scaffold-regenerated bone were found to be statistically equivalent to native bone ( P = 0.148 for reduced elastic modulus of scaffolds with and without caps and P = 0.228 and P = 0.902 for hardness of scaffolds with and without caps, respectively). CONCLUSION: 3DPBC-DIPY scaffolds have the capacity to regenerate bone across critically sized calvarial defects in a skeletally immature translational pig model. CLINICAL RELEVANCE STATEMENT: This study assessed the bone generative capacity of 3D-printed bioceramic scaffolds composed of 100% ß-tricalcium phosphate and augmented with dipyridamole placed within critical-sized calvarial defects in a growing porcine model.

The presence of 3D printing in orthopedics: A clinical and material review.

The field of additive manufacturing, 3D printing (3DP), has experienced an exponential growth over the past four decades, in part due to increased accessibility. Developments including computer-aided design and manufacturing, incorporation of more versatile materials, and improved printing techniques/equipment have stimulated growth of 3DP technologies within various industries, but most specifically the medical field. Alternatives to metals including ceramics and polymers have been garnering popularity due to their resorbable properties and physiologic similarity to extracellular matrix. 3DP has the capacity to utilize an assortment of materials and printing techniques for a multitude of indications, each with their own associated benefits. Within the field of medicine, advances in medical imaging have facilitated the integration of 3DP. In particular, the field of orthopedics has been one of the earliest medical specialties to implement 3DP. Current indications include education for patients, providers, and trainees, in addition to surgical planning. Moreover, further possibilities within orthopedic surgery continue to be explored, including the development of patient-specific implants. This review aims to highlight the use of current 3DP technology and materials by the orthopedic community, and includes comments on current trends and future direction(s) within the field.

Patient-specific 3D printed Poly-ether-ether-ketone (PEEK) dental implant system.

Fused Filament Fabrication (FFF)-based 3D printing is an efficient technique for developing medical implants, but it is not very useful in developing small yet mechanically robust design-specific fixtures such as dental implants (<15 mm). Specifically, it is challenging to 3D print robust Polyetheretherketone (PEEK) small implants due to PEEK's high melting temperature and melt viscosity. However, in this study, we efficiently utilize high-temperature FFF to develop the first-of-its-kind patient-specific robust PEEK dental implants with high print resolution. Specifically, we explore the effects of critical FFF processing conditions on the mechanical properties of the implants and subsequently determine an optimized set of processing conditions that are essential in developing durable dental implant systems. Our results indicate that the 3D printed dental implants exhibit good fatigue properties and suffice the clinical and industrial requirements for dental implants. Furthermore, we prove that the 3D printed implants exhibit adequate mechanical durability even after simulated (accelerated) aging of 30 years.

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.

Self-assembling human skeletal organoids for disease modeling and drug testing.

Skeletal conditions represent a considerable challenge to health systems globally. Barriers to effective therapeutic development include a lack of accurate preclinical tissue and disease models. Most recently, work was attempted to present a novel whole organ approach to modeling human bone and cartilage tissues. These self-assembling skeletal organoids mimic the cellular milieu and extracellular organization present in native tissues. Bone organoids demonstrated osteogenesis and micro vessel formation, and cartilage organoids showed evidence of cartilage development and maturation. Skeletal organoids derived from both bone and cartilage tissues yielded spontaneous polarization of their cartilaginous and bone components. Using these hybrid skeletal organoids, we successfully generated "mini joint" cultures, which we used to model inflammatory disease and test Adenosine (A2A ) receptor agonists as a therapeutic agent. The work and respective results indicated that skeletal organoids can be an effective biological model for tissue development and disease as well as to test therapeutic agents.

Residual stress estimated by nanoindentation in pontics and abutments of veneered zirconia fixed dental prostheses

Abstract Glass ceramics' fractures in zirconia fixed dental prosthesis (FDP) remains a clinical challenge since it has higher fracture rates than the gold standard, metal ceramic FDP. Nanoindentation has been shown a reliable tool to determine residual stress of ceramic systems, which can ultimately correlate to failure-proneness. Objectives: To assess residual tensile stress using nanoindentation in veneered three-unit zirconia FDPs at different surfaces of pontics and abutments. Methodology: Three composite resin replicas of the maxillary first premolar and crown-prepared abutment first molar were made to obtain three-unit FDPs. The FDPs were veneered with glass ceramic containing fluorapatite crystals and resin cemented on the replicas, embedded in epoxy resin, sectioned, and polished. Each specimen was subjected to nanoindentation in the following regions of interest: 1) Mesial premolar abutment (MPMa); 2) Distal premolar abutment (DPMa); 3) Buccal premolar abutment (BPMa); 4) Lingual premolar abutment (LPMa); 5) Mesial premolar pontic (MPMp); 6) Distal premolar pontic (DPMp); 7) Buccal premolar pontic (BPMp); 8) Lingual premolar pontic (LPMp); 9) Mesial molar abutment (MMa); 10) Distal molar abutment (DMa); 11) Buccal molar abutment (BMa); and 12) Lingual molar abutment (LMa). Data were assessed using Linear Mixed Model and Least Significant Difference (95%) tests. Results: Pontics had significantly higher hardness values than premolar (p=0.001) and molar (p=0.007) abutments, suggesting lower residual stress levels. Marginal ridges yielded higher hardness values for connectors (DPMa, MMa, MPMp and DPMp) than for outer proximal surfaces of abutments (MPMa and DMa). The mesial marginal ridge of the premolar abutment (MPMa) had the lowest hardness values, suggesting higher residual stress concentration. Conclusions: Residual stress in three-unit FDPs was lower in pontics than in abutments. The outer proximal surfaces of the abutments had the highest residual stress concentration.