Colour stability of 3D-Printed orthodontic brackets using filled resins.

OBJECTIVE: To determine the effect of common beverages and accelerated aging on the colour stability of filled resins, which could potentially be used for fabrication of 3D-printed orthodontic brackets. MATERIALS AND METHODS: GR-17.1 (shades A1, A2, and A3), and GR-10 Guide resins (pro3dure medical, Eden Prairie, MN) were printed on an Asiga MAX UV printer into discs 2 mm thick, with a diameter of 10 mm, and then post-print processed as per manufacturer's instructions. Discs were immersed in 5 mL of coffee, tea, red wine, or distilled water for 7 days. Another group was subjected to accelerated aging in accordance with ISO Standard 4892-2. Ten samples were produced per resin, per treatment condition. Colour measurements were taken on the discs before and after treatment using a spectrophotometer against white and black reference tiles to assess colour and translucency differences with the CIEDE2000 colour difference formula. RESULTS: While initial colour of the printed resin discs was acceptable, all resin groups underwent significant colour change during the experiment. Red wine and coffee produced the greatest colour and translucency change, followed by tea, with accelerated aging producing the least change in colour and translucency. CONCLUSION: The 3D-printed resins tested underwent significant changes in colour and translucency following exposure to endogenous and exogenous sources of staining, which may affect their acceptability for fabrication of aesthetic orthodontic brackets.

Effect of Material and Pad Abrasion on Shear Bond Strength of 3D-Printed Orthodontic Brackets.

OBJECTIVE: To investigate the effect of printing material and air abrasion of bracket pads on the shear bond strength of 3D-printed plastic orthodontic brackets when bonded to the enamel of extracted human teeth. MATERIALS AND METHODS: Premolar brackets were 3D-printed using the design of a commercially available plastic bracket in two biocompatible resins: Dental LT Resin and Dental SG Resin (n = 40/material). 3D-printed brackets and commercially manufactured plastic brackets were divided into two groups (n = 20/group), one of which was air abraded. All brackets were bonded to extracted human premolars, and shear bond strength tests were performed. The failure types of each sample were classified using a 5-category modified adhesive remnant index (ARI) scoring system. RESULTS: Bracket material and bracket pad surface treatment presented statistically significant effects for shear bond strengths, and a significant interaction effect between bracket material and bracket pad surface treatment was observed. The non-air abraded (NAA) SG group (8.87 ± 0.64 MPa) had a statistically significantly lower shear bond strength than the air abraded (AA) SG group (12.09 ± 1.23 MPa). In the manufactured brackets and LT Resin groups, the NAA and AA groups were not statistically significantly different within each resin. A significant effect of bracket material and bracket pad surface treatment on ARI score was observed, but no significant interaction effect between bracket material and pad treatment was found. CONCLUSION: 3D-printed orthodontic brackets presented clinically sufficient shear bond strengths both with and without AA prior to bonding. The effect of bracket pad AA on shear bond strength depends on the bracket material.

Effect of print orientation on the dimensional accuracy of orthodontic aligners printed 3-dimensionally.

INTRODUCTION: Fabrication of orthodontic aligners directly via 3-dimensional (3D) printing presents the potential to increase the efficiency of aligner production relative to traditional workflows; however tunable aspects of the 3D-printing process might affect the dimensional fidelity of the fabricated appliances. This study aimed to investigate the effect of print orientation on the dimensional accuracy of orthodontic aligners printed directly with a 3D printer. METHODS: A digitally designed aligner of 500 µm thickness was printed in 3D in Grey V4 (Formlabs, Somerville, Mass) resin at 8 angulations at 45° intervals (n = 10 per angulation) using a stereolithography 3D printer. Each aligner was scanned with an optical scanner, and all but the intaglio surface of each scan was digitally removed. Each resultant scan file was superimposed onto the isolated intaglio of the designed master aligner file. The dimensional deviation was quantified with Geomagic Control software (3D Systems, Rock Hill, SC), and data were analyzed using R statistical software (version 2018; R Core Team, Vienna, Austria) (P <0.05). RESULTS: Print angle showed a statistically significant effect on standard deviation, average positive deviation, absolute average negative deviation, and percentage of points out of bounds (tolerance bounds defined as ±250 µm) (P <0.05). Qualitative analysis of the 3D surface deviation maps indicated that the 0° and 90° groups showed less deviation and appeared to be the most accurate in the anterior regions. Overall, the majority of the print angle groups studied were not printed within clinically acceptable tolerance ranges, with the major exception being the 90° group, which printed nominally within clinically acceptable tolerance ranges. CONCLUSIONS: With the workflow applied, print orientation significantly affects the dimensional accuracy of directly 3D-printed orthodontic aligners. Within the limitations of this study, printing at the 90° angulation would be advised as it is the group with the most accurate prints relative to the 7 other orientations investigated, although not all differences were statistically significant.

Evaluation of current additive manufacturing systems for orthodontic 3-dimensional printing.

INTRODUCTION: The objective of this research was to evaluate and compare linear and surface accuracy of dental models fabricated using 3 different vat photopolymerization printing units: digital light synthesis (M2 Printer; Carbon, Redwood City, Calif), digital light processing (Juell 3D Flash OC; Park Dental Research, New York, NY), and stereolithography apparatus (Form 2; Formlabs Inc, Somerville, Mass), and a material jetting printing unit: PolyJet (Objet Eden 260VS; Stratasys, Eden Prairie, Minn). METHODS: Maxillary and mandibular dental arches of 20 patients with the American Board of Orthodontics Discrepancy Index scores ranging between 10 and 30 were scanned using an intraoral scanner. Stereolithographic files of each patient were printed via the 3-dimensional (3D) printers and were digitized again using a 3D desktop scanner to enable comparisons with the original scan data. One-sample t test and linear regression analyses were performed. To further graphically examine the accuracy between the different methods, Bland-Altman plots were computed. The level of significance was set at P <0.05. RESULTS: Bland-Altman analysis showed no fixed bias of one approach vs the other, and random errors were detected in all linear accuracy comparisons. When a 0.25 mm tolerance level was deemed acceptable for any positive or negative surface changes, only the models manufactured from digital light processing and PolyJet units showed more than 97% match with the original scans. CONCLUSION: The surface area of 3D printed models did not yield an utterly identical match to the original scan data and was affected by the type of printer. The clinical relevance of the differences observed on the 3D printed dental model surfaces requires application-specific judgments.

Effect of build angle and layer height on the accuracy of 3-dimensional printed dental models.

INTRODUCTION: Three-dimensional (3D) printing technologies are profoundly changing the landscape of orthodontics. To optimize treatment-oriented applications, dimensional fidelity is required for 3D-printed orthodontic models. This study aimed to evaluate the effect of build angle and layer height on the accuracy of 3D-printed dental models and if each of their influences on print accuracy was conditional on the other. METHODS: A maxillary cast was scanned using an intraoral scanner. One hundred thirty-two study models were printed at various combinations of build angle (0°, 30°, 60°, 90°) and layer height (20 µm, 50 µm, 100 µm) with a digital light processing printer (n = 11 per group). The models were digitally scanned, and deviation analyzed using a 3D best-fit algorithm in metrology software. RESULTS: A statistically significant interaction was consistently found between build angle and layer height for each positive deviation, negative deviation, and proportion out of bounds. Average deviations of all study models were within clinically acceptable ranges, but the least accurate models were printed at 0°/20 µm. Although there was a tendency for an oblique build angle of 30° or 60° with a smaller layer height of 20 µm or 50 µm to print the most accurate models, 95 % confidence intervals overlapped with all other angles and heights except for 0°/20 µm. CONCLUSIONS: Build angle and layer height have statistically significant interactive effects on the accuracy of 3D-printed dental models. Overall, digital light processing printers produced models within clinically acceptable bounds, but the choice of build angle and layer height should be considered in conjunction with the clinical application, desired print time, and preferred efficiency of each print job.

Colour stability of 3D-printed resin orthodontic brackets.

OBJECTIVE: To evaluate the colour stability of polymeric resins that could be used to 3D-print orthodontic brackets. DESIGN: In vitro, laboratory study. MATERIALS AND METHODS: Disc-shaped specimens were fabricated via 3D printing using three resins: Dental LT; Dental SG; and Clear. Five conditions were evaluated for each resin (n = 10 per treatment per resin) to assess its corresponding effect on colour and translucency: immersion in (1) red wine, (2) coffee, (3) tea and (4) distilled water (control), and (5) exposure to accelerated aging. Colour and translucency measurements were made before and after exposure using a spectrophotometer. Mean colour differences (ΔE00) and changes in translucency parameter (ΔTP00) were calculated for each sample using the CIEDE2000 colour difference formula. RESULTS: Statistically significant effects of the resin material, the treatment condition and interactions effects of material and condition were observed for ΔE00 and ΔTP00 (P < 0.001). The most pronounced changes in colour (ΔE00) were a result of the staining effects of wine on all three resins, ranging from 14.5 ± 0.6 to 20.8 ± 1.2. Dental LT, Dental SG and Clear resins all showed changes in colour when exposed to certain staining agents. Dental SG and Clear resins exhibited changes in colour with aging, while the colour of Dental LT resin remained stable with aging. CONCLUSIONS: The colour changes of the resins investigated does not support their use in 3D-printed aesthetic bracket applications.

Wear Resistance of 3D Printed and Prefabricated Denture Teeth Opposing Zirconia.

PURPOSE: To evaluate the wear resistance of a recently developed three-dimensional (3D) printed denture teeth resin compared to three commercially available prefabricated denture teeth. MATERIALS AND METHODS: A total of 88 maxillary first molar denture teeth were evaluated: C (Classic; Dentsply Sirona, York, PA), DCL (SR Postaris DCL; Ivoclar Vivadent, Schaan, Liechtenstein), IPN (Portrait IPN; Dentsply Sirona, York, PA), and F (Denture Teeth A2 Resin 1 L; Formlabs, Somerville, MA). The 3D printed denture tooth specimens were fabricated from a methacrylate-based photopolymerizing resin using stereolithography (SLA). Denture teeth were subjected to a three-body wear test with a poly(methylmethacrylate) (PMMA) abrasive slurry. A Leinfelder-style four station wear apparatus with custom bullet-shaped milled zirconia styli was utilized with a load force of 36-40 N at 1.7 Hz for 200,000 cycles. Maximum depth of wear was measured using a lab grade scanner and analyzing software program. Data were analyzed using a one-way ANOVA followed by the Tukey's Multiple Comparisons post hoc test (α = 0.05). RESULTS: A statistically significant difference in depth of wear was found between denture tooth materials (p < 0.001). The mean vertical depth of wear for the 3D printed denture teeth (0.016 ± 0.010 mm) was statistically significantly less than the prefabricated denture teeth. The highly cross-linked denture teeth, DCL (0.036 ± 0.011 mm) and IPN (0.035 ± 0.014 mm), exhibited statistically significantly less wear than the conventional acrylic denture teeth. The conventional acrylic denture teeth demonstrated the greatest wear (0.058 ± 0.014 mm). No significant difference in depth of wear was found between DCL and IPN (p > 0.001). CONCLUSIONS: Denture tooth material significantly influences the depth of wear. The 3D printed denture teeth demonstrated superior wear resistance compared to the commercially available prefabricated denture teeth when opposed to zirconia. Denture teeth fabricated with SLA technology may have a promising future in prosthetic dentistry.

Effect of Radiation on DCE-MRI Pharmacokinetic Parameters in a Rabbit Model of Compromised Maxillofacial Wound Healing: A Pilot Study.

PURPOSE: Osteoradionecrosis (ORN), a potentially debilitating complication of maxillofacial radiation, continues to present a challenging clinical scenario, with limited treatment options that often fail. Translational animal models that can accurately mimic the human characteristics of the condition are lacking. In the present pilot study, we aimed to characterize the effects of radiation on the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) pharmacokinetic parameters in a rabbit model of compromised maxillofacial wound healing to determine its potential as a translational model of ORN. MATERIALS AND METHODS: An experimental group underwent fractionated radiation of the mandible totaling 36 Gy. At 4 weeks after irradiation, the experimental and control groups (n = 8 rabbits each) underwent a surgical procedure to create a critical size defect in the mandibular bone. DCE-MRI scans were acquired 1 week after arrival (baseline; time point 1), 4 weeks after completion of irradiation in the experimental group (just before surgery, time point 2), and 4 weeks after surgery (time point 3). RESULTS: No differences in the analyzed DCE-MRI parameters were noted within the experimental or control group between the baseline values (time point 1) and those after irradiation (time point 2). The whole blood volume fraction (vb) in the experimental group was increased compared with that in the control group after irradiation (time point 2; P < .05). After surgery (time point 3), both the forward flux rate of contrast from blood plasma and the extracellular extravascular space and the vb were increased in the control group compared with the experimental group (P < .05). CONCLUSIONS: The results of the present study suggest that DCE-MRI of a rabbit model of compromised maxillofacial wound healing could reflect the DCE-MRI characteristics of human patients with ORN and those at risk of developing the condition. Future studies will focus on further characterization of this rabbit model as a translational preclinical model of ORN.

Analysis of the thickness of 3-dimensional-printed orthodontic aligners.

INTRODUCTION: This study aimed to investigate the effect of digitally designed aligner thickness on the thickness of the corresponding 3-dimensional (3D)-printed aligner. METHODS: Digitally designed aligners of 3 different thicknesses (0.500 mm, 0.750 mm, and 1.000 mm) were 3D printed in 2 different resins-Dental LT (n = 10 per group) and Grey V4 (n = 10 per group)-using a stereolithography format 3D printer. The Dental LT aligners were coated with a contrast spray and scanned with an optical scanner. The Grey V4 aligners were scanned before and after the application of the spray. Aligner scans were superimposed onto the corresponding digital design file. Average wall thickness across the aligner for each specimen was measured with metrology software. RESULTS: Superimpositions showed that 3D-printed aligners were thicker overall than the corresponding design file. The Dental LT aligners had the largest thickness deviation, whereas the Grey V4 without spray had the smallest. For the 0.500-mm, 0.750-mm, and 1.000-mm groups, Dental LT average thickness deviation from the input file was 0.254 ± 0.061 mm, 0.267 ± 0.052 mm, and 0.274 ± 0.034 mm, respectively, and average thickness differences between the Grey V4 with and without spray was 0.076 ± 0.016 mm, 0.070 ± 0.036 mm, and 0.080 ± 0.017 mm, respectively. These results indicate that the excess thickness in the Dental LT groups could not be attributed to spray alone. CONCLUSIONS: Fabrication of clear aligners directly by 3D printing with the workflow applied resulted in an increased thickness that may deleteriously affect the clinical utility of the aligners.

Efficacy of the mini tooth positioner in improving orthodontic finishes.

INTRODUCTION: The primary objective of this study was to assess the effectiveness of the mini tooth positioner in improving the quality of orthodontic treatment outcomes, as measured by the American Board of Orthodontics (ABO) cast-radiograph evaluation (CRE). METHODS: Thirty patients were treated prospectively with a minipositioner for 4-6 weeks immediately after debond. Sixteen patients who had received a maxillary vacuum-formed retainer (VFR) and fixed mandibular canine-to-canine retainer at time of debond were enrolled retrospectively as control subjects. Models from time of debond (T1) were graded with the use of the ABO CRE and compared with models obtained 4-6 weeks after debond (T2) for each group. RESULTS: For the minipositioner group, the overall CRE score improved significantly by an average of 6.77 points. Significant improvements were noted in the categories of alignment and rotations (-0.68), marginal ridges (-1.40), buccolingual inclination (-0.45), overjet (-0.97), and occlusal contacts (-3.00). For the control group, overall CRE score improved significantly by an average of 1.16 points. Only the categories of overjet (-0.38) and occlusal contacts (-1.22) showed significant improvements. CONCLUSIONS: The minipositioner is an effective tool in improving the overall finish of orthodontic treatment. In the 4-6 weeks after debond evaluated in this study, the minipositioner significantly outperformed the maxillary VFR/mandibular fixed canine-to-canine retainer in improving final treatment outcomes.

Effect of print layer height on the assessment of 3D-printed models.

INTRODUCTION: Many variables can affect the accuracy of 3D-printed orthodontic models, and the effects of different printing parameters on the clinical utility of the printed models are just beginning to be understood. The objective of this study was to investigate the effect of print layer height on the assessment of 3D-printed orthodontic models with the use of the American Board of Orthodontics Cast-Radiograph Evaluation grading system. METHODS: Twelve cases were scanned using a desktop model scanner and 3D-printed using a stereolithography-based printer at three different layer heights (25, 50, and 100-µm; n = 12 per group). All models were scored by eleven graders using the Cast-Radiograph Evaluation grading system. All models were scored a second time, at least two weeks later. RESULTS: No statistically significant effects of print layer height were found on the scoring of the models for any of the grading metrics or total score. 3D-printed models of each layer height were highly positively correlated with stone models for the total score, with the strongest correlation found with models printed at 100-µm. CONCLUSIONS: 100-µm layer height 3D-printed models are potentially clinically acceptable for the purposes of evaluation of treatment outcomes, diagnosis and treatment planning, and residency training.

Comparison of automated grading of digital orthodontic models and hand grading of 3-dimensionally printed models.

INTRODUCTION: Emerging workflows in orthodontics enable automated analysis of digital models and production of physical study models from digital files for the evaluation of treatment outcomes. The objective of this study was to compare the automated assessment of digital orthodontic models and the hand grading of 3D-printed models with the use of the American Board of Orthodontics cast-radiograph evaluation (ABO CRE) system. METHODS: Plaster models from 15 cases were scanned with the use of a desktop model scanner to create digital models from which physical models were produced with the use of a stereolithography-based 3D printer. All digital models from each case were graded with the use of an automated software tool (SureSmile), and 3D-printed models were scored by hand with the use of the ABO CRE grading system. All hand-graded models were scored a second time at least 2 weeks later. RESULTS: SureSmile gave statistically significantly higher scores to alignment and rotations (P < 0.001), overjet (P < 0.001), occlusal contacts (P < 0.001), and total score (P < 0.001). Hand grading scored higher in buccolingual inclination (P < 0.001). No significant differences were found in marginal ridges, occlusal relationships, and interproximal contacts. CONCLUSIONS: Scores assessed in an automated manner by SureSmile are generally significantly greater than those assessed by hand grading.

Silver diamine fluoride and bond strength to enamel in vitro: A pilot study.

PURPOSE: To evaluate if pre-treatment with silver diamine fluoride (SDF) adversely affects the bond strength of orthodontic brackets to enamel. METHODS: 30 extracted non-carious permanent molar teeth were embedded in acrylic resin cylinders with buccal surfaces exposed and randomly divided equally into two groups. The experimental enamel surfaces were treated with 38% SDF applied for 1 minute between phosphoric acid etch and metal orthodontic bracket bonding with Transbond XT Light Cure Adhesive. Control groups were treated with 37% phosphoric acid etch followed by bonding. All samples were subjected to 500 thermocycles between 5°C and 55°C prior to shear load testing. Mean values and standard deviations of shear bond strengths for each group were analyzed using a general linear model at P< 0.05. Characteristics of bond failure were also recorded via Adhesive Remnant Index (ARI) and analyzed using an ordinal logistic regression at P< 0.05. RESULTS: No significant difference in shear bond strength to enamel was observed between the control and experimental groups (P= 0.65). Comparison of ARI did demonstrate a significant difference between the groups (P= 0.013); SDF significantly altered the characteristic of bond failure, resulting in more adhesive remaining bonded to enamel after failure. No silver staining of treated surfaces was observed. CLINICAL SIGNIFICANCE: The application of SDF to etched non-carious enamel in vitro prior to orthodontic bracket bonding does not adversely affect bond strength.

Effect of print layer height and printer type on the accuracy of 3-dimensional printed orthodontic models.

INTRODUCTION: Three-dimensional (3D) printing technologies enable production of orthodontic models from digital files; yet a range of variables associated with the process could impact the accuracy and clinical utility of the models. The objective of this study was to investigate the effect of print layer height on the accuracy of orthodontic models printed 3 dimensionally using a stereolithography format printer and to compare the accuracy of orthodontic models fabricated with several commercially available 3D printers. METHODS: Thirty-six identical models were produced with a stereolithography-based 3D printer using 3 layer heights (n = 12 per group): 25, 50, and 100 µm. Forty-eight additional models were printed using 4 commercially available 3D printers (n = 12 per group). Each printed model was digitally scanned and compared with the input file via superimposition analysis using a best-fit algorithm to assess accuracy. RESULTS: Statistically significant differences were found in the average overall deviations of models printed at each layer height, with the 25-µm and 100-µm layer height groups having the greatest and least deviations, respectively. Statistically significant differences were also found in the average overall deviations of models produced using the various 3D printer models, but all values fell within clinically acceptable limits. CONCLUSIONS: The print layer height and printer model can affect the accuracy of a 3D printed orthodontic model, but the impact should be considered with respect to the clinical tolerances associated with the envisioned application.

Modeling Ewing sarcoma tumors in vitro with 3D scaffolds.

The pronounced biological influence of the tumor microenvironment on cancer progression and metastasis has gained increased recognition over the past decade, yet most preclinical antineoplastic drug testing is still reliant on conventional 2D cell culture systems. Although monolayer cultures recapitulate some of the phenotypic traits observed clinically, they are limited in their ability to model the full range of microenvironmental cues, such as ones elicited by 3D cell-cell and cell-extracellular matrix interactions. To address these shortcomings, we established an ex vivo 3D Ewing sarcoma model that closely mimics the morphology, growth kinetics, and protein expression profile of human tumors. We observed that Ewing sarcoma cells cultured in porous 3D electrospun poly(ε-caprolactone) scaffolds not only were more resistant to traditional cytotoxic drugs than were cells in 2D monolayer culture but also exhibited remarkable differences in the expression pattern of the insulin-like growth factor-1 receptor/mammalian target of rapamycin pathway. This 3D model of the bone microenvironment may have broad applicability for mechanistic studies of bone sarcomas and exhibits the potential to augment preclinical evaluation of antineoplastic drug candidates for these malignancies.

Accuracy and mechanical properties of orthodontic models printed 3-dimensionally from calcium sulfate before and after various postprinting treatments.

INTRODUCTION: Dental models fabricated with 3-dimensional printing technologies are revolutionizing the practice of orthodontics, but they generally comprise polymeric materials that may not be suitable for certain applications, such as soldering appliances. The objective of this study was to investigate the dimensional accuracy and mechanical properties of 3-dimensional printed ceramic-based models before and after various treatments intended to improve their mechanical properties. METHODS: Thirty identical models were printed 3-dimensionally from a calcium sulfate-based substrate and divided into 3 groups for treatment: high heat (250°C for 30 minutes), low heat (150°C for 30 minutes), and Epsom salt treatment. Each model was scanned before and after treatment with a laser scanner, and dimensional stability was analyzed by digital superimpositions using a best-fit algorithm. The models were weighed before and after treatment to evaluate mass changes. Additionally, 3-dimensional printed cylinders treated as described above and an untreated control group were subjected to compressive mechanical testing (n = 11 per group). RESULTS: The Epsom salt treatment group had statistically significant increases in both peak compressive stress and modulus of elasticity when compared with the other treatment groups. All treatment groups had statistically significant changes in mass, with the Epsom salt group gaining mass and the 2 heat-treatment groups losing mass. The low-temperature treatment group had a statistically significantly lower mean average for dimensional deviations (0.026 ± 0.010 mm) than did the other treatment groups (0.069 ± 0.006 and 0.059 ± 0.010 mm for high temperature and Epsom salt, respectively). CONCLUSIONS: Dental models printed 3-dimensionally with calcium sulfate and treated with Epsom salt showed significant improvement in compressive mechanical properties and retained clinically acceptable dimensional stability.

Synthesis, physicochemical characterization, and cytocompatibility of bioresorbable, dual-gelling injectable hydrogels.

Injectable, dual-gelling hydrogels were successfully developed through the combination of physical thermogellation at 37 °C and favorable amine:epoxy chemical cross-linking. Poly(N-isopropylacrylamide)-based thermogelling macromers with a hydrolyzable lactone ring and epoxy pendant groups and a biodegradable diamine-functionalized polyamidoamine cross-linker were synthesized, characterized, and combined to produce nonsyneresing and bioresorbable hydrogels. Differential scanning calorimetry and oscillatory rheometry demonstrated the rapid and dual-gelling nature of the hydrogel formation. The postgelation dimensional stability, swelling, and mechanical behavior of the hydrogel system were shown to be easily tuned in the synthesis and formulation stages. The leachable products were found to be cytocompatible under all conditions, while the degradation products demonstrated a dose- and time-dependent response due to solution osmolality. Preliminary encapsulation studies showed mesenchymal stem cell viability could be maintained for 7 days. The results suggest that injectable and thermally and chemically cross-linkable hydrogels are promising alternatives to prefabricated biomaterials for tissue engineering applications, particularly for cell delivery.

Synthesis and characterization of injectable, biodegradable, phosphate-containing, chemically cross-linkable, thermoresponsive macromers for bone tissue engineering.

Novel, injectable, biodegradable macromer solutions that form hydrogels when elevated to physiologic temperature via a dual chemical and thermo-gelation were fabricated and characterized. A thermogelling, poly(N-isopropylacrylamide)-based macromer with pendant phosphate groups was synthesized and subsequently functionalized with chemically cross-linkable methacrylate groups via degradable phosphate ester bonds, yielding a dual-gelling macromer. These dual-gelling macromers were tuned to have transition temperatures between room temperature and physiologic temperature, allowing them to undergo instantaneous thermogelation as well as chemical gelation when elevated to physiologic temperature. Additionally, the chemical cross-linking of the hydrogels was shown to mitigate hydrogel syneresis, which commonly occurs when thermogelling materials are raised above their transition temperature. Finally, degradation of the phosphate ester bonds of the cross-linked hydrogels yielded macromers that were soluble at physiologic temperature. Further characterization of the hydrogels demonstrated minimal cytotoxicity of hydrogel leachables as well as in vitro calcification, making these novel, injectable macromers promising materials for use in bone tissue engineering.