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Since three-dimensional (3D) bioprinting has emerged, it has continuously to evolved as a revolutionary technology in surgery, offering new paradigms for reconstructive and regenerative medical applications. This review highlights the integration of 3D printing, specifically bioprinting, across several surgical disciplines over the last five years. The methods employed encompass a review of recent literature focusing on innovations and applications of 3D-bioprinted tissues and/or organs. The findings reveal significant advances in the creation of complex, customized, multi-tissue constructs that mimic natural tissue characteristics, which are crucial for surgical interventions and patient-specific treatments. Despite the technological advances, the paper introduces and discusses several challenges that remain, such as the vascularization of bioprinted tissues, integration with the host tissue, and the long-term viability of bioprinted organs. The review concludes that while 3D bioprinting holds substantial promise for transforming surgical practices and enhancing patient outcomes, ongoing research, development, and a clear regulatory framework are essential to fully realize potential future clinical applications.

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Periodontitis is a bacteria-induced chronic inflammatory disease characterized by degradation of the supporting tissue and bone in the oral cavity. Treatment modalities seek to facilitate periodontal rehabilitation while simultaneously preventing further gingival tissue recession and potentially bone atrophy. The aim of this study was to compare two differently sourced membranes, a resorbable piscine collagen membrane and a porcine-derived collagen membrane, in the repair of soft tissue defects utilizing a preclinical canine model. This in vivo component consisted of 10 beagles which were subjected to bilateral maxillary canine mucogingival flap defects, as well as bilateral soft tissue defects (or pouches) with no periodontal ligament damage in the mandibular canines. Defects received either a piscine-derived dermal membrane, (Kerecis® Oral, Ísafjörður, Iceland) or porcine-derived dermal membrane (Geistlich Mucograft®, Wolhusen, Switzerland) in a randomized fashion (to avoid site bias) and were allowed to heal for 30, 60, or 90 days. Statistical evaluation of tissue thickness was performed using general linear mixed model analysis of variance and least significant difference (LSD) post hoc analyses with fixed factors of time and membrane. Semi-quantitative analysis employed for inflammation assessment was evaluated using a chi-squared test along with a heteroscedastic t-test and values were reported as mean and corresponding 95% confidence intervals. In both the mucogingival flap defects and soft tissue gingival pouches, no appreciable qualitative differences were observed in tissue healing between the membranes. Furthermore, no statistical differences were observed in the thickness measurements between piscine- and porcine-derived membranes in the mucogingival flap defects (1.05 mm [±0.17] and 1.29 mm [±0.17], respectively [p = .06]) or soft tissue pouches (1.36 mm [±0.14] and 1.47 mm [±0.14], respectively [p = .27]), collapsed over time. Independent of membrane source (i.e., piscine or porcine), similar inflammatory responses were observed in both the maxilla and mandible at the three time points (p = .88 and p = .79, respectively). Histologic and histomorphometric evaluation results indicated that both membranes yielded equivalent tissue responses, remodeling dynamics and healing patterns for the mucogingival flap as well as the soft tissue gingival pouch defect models.

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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.

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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.

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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.

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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.

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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.

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The energy state of endosteal implants is dependent on the material, manufacturing technique, cleaning procedure, sterilization method, and surgical manipulation. An implant surface carrying a positive charge renders hydrophilic properties, thereby facilitating the absorption of vital plasma proteins crucial for osteogenic interactions. Techniques to control the surface charge involve processes like oxidation, chemical and topographical adjustments as well as the application of nonthermal plasma (NTP) treatment. NTP at atmospheric pressure and at room temperature can induce chemical and/or physical reactions that enhance wettability through surface energy changes. NTP has thus been used to modify the oxide layer of endosteal implants that interface with adjacent tissue cells and proteins. Results have indicated that if applied prior to implantation, NTP strengthens the interaction with surrounding hard tissue structures during the critical phases of early healing, thereby promoting rapid bone formation. Also, during this time period, NTP has been found to result in enhanced biomechanical fixation. As such, the application of NTP may serve as a practical and reliable method to improve healing outcomes. This review aims to provide an in-depth exploration of the parameters to be considered in the application of NTP on endosteal implants. In addition, the short- and long-term effects of NTP on osseointegration are addressed, as well as recent advances in the utilization of NTP in the treatment of periodontal disease.

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Non-union during healing of bone fractures affects up to ~5% of patients worldwide. Given the success of recombinant human platelet-derived growth factor-B chain homodimer (rhPDGF-BB) in promoting angiogenesis and bone fusion in the hindfoot and ankle, rhPDGF-BB combined with bovine type I collagen/ß-TCP matrix (AIBG) could serve as a viable alternative to autografts in the treatment of non-unions. Defects (~2 mm gaps) were surgically induced in tibiae of skeletally mature New Zealand white rabbits. Animals were allocated to one of four groups-(1) negative control (empty defect, healing for 8 weeks), (2 and 3) acute treatment with AIBG (healing for 4 or 8 weeks), and (4) chronic treatment with AIBG (injection 4 weeks post defect creation and then healing for 8 weeks). Bone formation was analyzed qualitatively and semi-quantitatively through histology. Samples were imaged using dual-energy X-ray absorptiometry and computed tomography for defect visualization and volumetric reconstruction, respectively. Delayed healing or non-healing was observed in the negative control group, whereas defects treated with AIBG in an acute setting yielded bone formation as early as 4 weeks with bone growth appearing discontinuous. At 8 weeks (acute setting), substantial remodeling was observed with higher degrees of bone organization characterized by appositional bone growth. The chronic healing, experimental, group yielded bone formation and remodeling, with no indication of non-union after treatment with AIBG. Furthermore, bone growth in the chronic healing group was accompanied by an increased presence of osteons, osteonal canals, and interstitial lamellae. Qualitatively and semiquantitatively, chronic application of AI facilitated complete bridging of the induced non-union defects, while untreated defects or defects treated acutely with AIBG demonstrated a lack of complete bridging at 8 weeks.

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BACKGROUND: ß-tricalcium phosphate (ß-TCP) has been successfully utilized as a 3D printed ceramic scaffold in the repair of non-healing bone defects; however, it requires the addition of growth factors to augment its regenerative capacity. Synthetic bone mineral (SBM) is a novel and extrudable carbonate hydroxyapatite with ionic substitutions known to facilitate bone healing. However, its efficacy as a 3D printed scaffold for hard tissue defect repair has not been explored. OBJECTIVE: To evaluate the biocompatibility and cell viability of human osteoprecursor (hOP) cells seeded on 3D printed SBM scaffolds via in vitro analysis. METHODS: SBM and ß-TCP scaffolds were fabricated via 3D printing and sintered at various temperatures. Scaffolds were then subject to qualitative cytotoxicity testing and cell proliferation experiments utilizing (hOP) cells. RESULTS: SBM scaffolds sintered at lower temperatures (600 °C and 700 °C) induced greater levels of acute cellular stress. At higher sintering temperatures (1100 °C), SBM scaffolds showed inferior cellular viability relative to ß-TCP scaffolds sintered to the same temperature (1100 °C). However, qualitative analysis suggested that ß-TCP presented no evidence of morphological change, while SBM 1100 °C showed few instances of acute cellular stress. CONCLUSION: Results demonstrate SBM may be a promising alternative to ß-TCP for potential applications in bone tissue engineering.

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