Faculty Bibliography

Bone tissue regeneration is a rapidly evolving field aimed at the development of biocompatible materials and devices, such as scaffolds, to treat diseased and damaged osseous tissue. Functional scaffolds maintain structural integrity and provide mechanical support at the defect site during the healing process, while simultaneously enabling or improving regeneration through amplified cellular cues between the scaffold and native tissues. Ample research on functionalization has been conducted to improve scaffold-host tissue interaction, including fabrication techniques, biomaterial selection, scaffold surface modifications, integration of bioactive molecular additives, and post-processing modifications. Each of these methods plays a crucial role in enabling scaffolds to not only support but actively participate in the healing and regeneration process in bone and joint surgery. This review provides a state-of-the-art, comprehensive overview of the functionalization of scaffold-based strategies used in tissue engineering, specifically for bone regeneration. Critical issues and obstacles are highlighted, applications and advances are described, and future directions are identified.

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.

Surface pre-reacted glass-ionomer (S-PRG) is a new bioactive filler utilized for the restoration of decayed teeth by its ability to release six bioactive ions that prevent the adhesion of dental plaque to the tooth surface. Since ionic liquids are reported to facilitate transepithelial penetration, we reasoned that S-PRG applied to root caries could impact the osteoclasts (OCs) in the proximal alveolar bone. Therefore, this study aimed to investigate the effect of S-PRG eluate solution on RANKL-induced OC-genesis and mineral dissolution in vitro. Using RAW264.7 cells as OC precursor cells (OPCs), TRAP staining and pit formation assays were conducted to monitor OC-genesis and mineral dissolution, respectively, while OC-genesis-associated gene expression was measured using quantitative real-time PCR (qPCR). Expression of NFATc1, a master regulator of OC differentiation, and the phosphorylation of MAPK signaling molecules were measured using Western blotting. S-PRG eluate dilutions at 1/200 and 1/400 showed no cytotoxicity to RAW264.7 cells but did significantly suppress both OC-genesis and mineral dissolution. The same concentrations of S-PRG eluate downregulated the RANKL-mediated induction of OCSTAMP and CATK mRNAs, as well as the expression of NFATc1 protein and the phosphorylation of ERK, JNK, and p38. These results demonstrate that S-PRG eluate can downregulate RANKL-induced OC-genesis and mineral dissolution, suggesting that its application to root caries might prevent alveolar bone resorption.

The purpose of this in vitro study was to develop calcium sulfate (CS)-based disks infused with an antimicrobial drug, which can be used as a post-surgical treatment modality for osteomyelitis. CS powder was embedded with 10% antibiotic, amoxicillin (AMX) or moxifloxacin (MFX), to form composite disks 11 mm in diameter that were tested for their degradation and antibiotic release profiles. For the disk degradation study portion, the single drug-loaded disks were placed in individual meshes, subsequently submerged in phosphate-buffered saline (PBS), and incubated at 37 °C. The disks were weighed once every seven days and analyzed via Fourier-transform infrared spectroscopy, X-ray diffraction, energy dispersive X-ray spectroscopy, and scanning electron microscopy. During the antibiotic release analysis, composite disks were placed in PBS solution, which was changed every 3 days, and analyzed for antibiotic activity and efficacy. The antibacterial effects of these sustained-release composites were tested by agar diffusion assay using Streptococcus mutans (S. mutans) UA 159 as an indicator strain. The degradation data showed significant increases in the degradation of all disks with the addition of antibiotics. Following PBS incubation, there were significant increases in the amount of phosphate and decreases in the amount of sulfate. The agar diffusion assay demonstrated that the released concentrations of the respective antibiotics from the disks were significantly higher than the minimum inhibitory concentration exhibited against S. mutans over a 2-3-week period. In conclusion, CS-antibiotic composite disks can potentially serve as a resorbable, osteoconductive, and antibacterial therapy in the treatment of bone defects and osteomyelitis.

OBJECTIVES/OBJECTIVE:To evaluate the effects of dentin biomodification agents (Proanthocyanidin (PAC), Cardol (CD) and Cardol-methacrylate (CDMA) on dentin hydrophilicity by contact angle measurement, viability of dental pulp stem cells (DPSCs) and nanomechanical properties of the hybrid layer (HL). METHODS:CDMA monomer was synthesized from cardol through methacrylic acid esterification. Human extracted third molars were used for all experiments. For nanomechanical tests, specimens were divided in four groups according to the primer solutions (CD, CDMA, PAC and control) were applied before adhesive and composite coating. Nanomechanical properties of the HL were analyzed by nanoindentation test using a Berkovich probe in a nanoindenter. Wettability test was performed on dentin surfaces after 1 min biomodification and measured by contact angle analysis. Cytotoxicity was assessed by a MTT assay with DPSCs after 48 and 72 h. Data were analyzed with Student's t test or Two-way ANOVA and Tukey HSD test (p < 0.05). RESULTS:CD and CDMA solutions achieved greater hydrophobicity and increased the water-surface contact angles when compared to PAC and control groups (p < 0.05). PAC group showed a greater reduction of elastic modulus in nanoindentation experiments when compared to CD and CDMA groups (p < 0.05) after 4 months of aging. CD inhibited cell proliferation compared to all further materials (p < 0.05), whilst CDMA and PAC indicated no cell cytotoxicity to human DPSCs. SIGNIFICANCE/CONCLUSIONS:Cardol-methacrylate provided significantly higher hydrophobicity to dentin and demonstrated remarkable potential as collagen crosslinking, attaining the lowest decrease of HL's mechanical properties. Furthermore, such monomer did not affect pulp cytotoxicity, thereby highlighting promising feasibility for clinical applications.

The present work aims to develop a production method of pre-sintered zirconia-toughened-alumina (ZTA) composite blocks for machining in a computer-aided design and computer-aided manufacturing (CAD-CAM) system. The ZTA composite comprised of 80% Al₂O₃ and 20% ZrO₂ was synthesized, uniaxially and isostatically pressed to generate machinable CAD-CAM blocks. Fourteen green-body blocks were prepared and pre-sintered at 1000 °C. After cooling and holder gluing, a stereolithography (STL) file was designed and uploaded to manufacture disk-shaped specimens projected to comply with ISO 6872:2015. Seventy specimens were produced through machining of the blocks, samples were sintered at 1600 °C and two-sided polished. Half of the samples were subjected to accelerated autoclave hydrothermal aging (20h at 134 °C and 2.2 bar). Immediate and aged samples were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Optical and mechanical properties were assessed by reflectance tests and by biaxial flexural strength test, Vickers indentation and fracture toughness, respectively. Samples produced by machining presented high density and smooth surfaces at SEM evaluation with few microstructural defects. XRD evaluation depicted characteristic peaks of alpha alumina and tetragonal zirconia and autoclave aging had no effect on the crystalline spectra of the composite. Optical and mechanical evaluations demonstrated a high masking ability for the composite and a characteristic strength of 464 MPa and Weibull modulus of 17, with no significant alterations after aging. The milled composite exhibited a hardness of 17.61 GPa and fracture toughness of 5.63 MPa m^1/2, which remained unaltered after aging. The synthesis of ZTA blocks for CAD-CAM was successful and allowed for the milling of disk-shaped specimens using the grinding method of the CAD-CAM system. ZTA composite properties were unaffected by hydrothermal autoclave aging and present a promising alternative for the manufacture of infrastructures of fixed dental prostheses.

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/β-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.

This review focuses on advancements in polymer science as it relates to three-dimensional (3D) and four-dimensional (4D) printing technologies, with a specific emphasis on applications in the biomedical field. While acknowledging the breadth of 3D and 4D printing applications, this paper concentrates on the use of polymers in creating biomedical devices and the challenges associated with their implementation. It explores integrative modeling and experimental insights driving innovations in these fields, focusing on sustainable manufacturing with biodegradable polymers, a comparative analysis of 3D and 4D printing techniques, and applications in biomedical devices. Additionally, the review examines the materials used in both 3D and 4D printing, offering a detailed comparison of their properties and applications. By highlighting the transformative potential of these technologies in various industrial and medical applications, the paper underscores the importance of continued research and development. The scope of this review also includes an overview of future research directions to address current challenges, enhance material capabilities, and explore practical applications.

BACKGROUND/UNASSIGNED:β-tricalcium phosphate (β-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/UNASSIGNED:To evaluate the biocompatibility and cell viability of human osteoprecursor (hOP) cells seeded on 3D printed SBM scaffolds via in vitro analysis. METHODS/UNASSIGNED:SBM and β-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/UNASSIGNED: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 β-TCP scaffolds sintered to the same temperature (1100 °C). However, qualitative analysis suggested that β-TCP presented no evidence of morphological change, while SBM 1100 °C showed few instances of acute cellular stress. CONCLUSION/UNASSIGNED:Results demonstrate SBM may be a promising alternative to β-TCP for potential applications in bone tissue engineering.

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.