Direct inkjet writing type 1 bovine collagen/ß-tricalcium phosphate scaffolds for bone regeneration.

Bone tissue has the capacity to regenerate under healthy conditions, but complex cases like critically sized defects hinder natural bone regeneration, necessitating surgery, and use of a grafting material for rehabilitation. The field of bone tissue engineering (BTE) has pioneered ways to address such issues utilizing different biomaterials to create a platform for cell migration and tissue formation, leading to improved bone reconstruction. One such approach involves 3D-printed patient-specific scaffolds designed to aid in regeneration of boney defects. This study aimed to develop and characterize 3D printed scaffolds composed of type I collagen augmented with ß-tricalcium phosphate (COL/ß-TCP). A custom-built direct inkjet write (DIW) printer was used to fabricate ß-TCP, COL, and COL/ß-TCP scaffolds using synthesized colloidal gels. After chemical crosslinking, the scaffolds were lyophilized and subjected to several characterization techniques, including light microscopy, scanning electron microscopy, and x-ray diffraction to evaluate morphological and chemical properties. In vitro evaluation was performed using human osteoprogenitor cells to assess cytotoxicity and proliferative capacity of the different scaffold types. Characterization results confirmed the presence of ß-TCP in the 3D printed COL/ß-TCP scaffolds, which exhibited crystals that were attributed to ß-TCP due to the presence of calcium and phosphorus, detected through energy dispersive x-ray spectroscopy. In vitro studies showed that the COL/ß-TCP scaffolds yielded more favorable results in terms of cell viability and proliferation compared to ß-TCP and COL scaffolds. The novel COL/ß-TCP scaffold constructs hold promise for improving BTE applications and may offer a superior environment for bone regeneration compared with conventional COL and ß-TCP scaffolds.

3D printed ß-tricalcium phosphate versus synthetic bone mineral scaffolds: A comparative in vitro study of biocompatibility.

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.

3D Printing Type 1 Bovine Collagen Scaffolds for Tissue Engineering Applications-Physicochemical Characterization and In Vitro Evaluation.

Collagen, an abundant extracellular matrix protein, has shown hemostatic, chemotactic, and cell adhesive characteristics, making it an attractive choice for the fabrication of tissue engineering scaffolds. The aim of this study was to synthesize a fibrillar colloidal gel from Type 1 bovine collagen, as well as three dimensionally (3D) print scaffolds with engineered pore architectures. 3D-printed scaffolds were also subjected to post-processing through chemical crosslinking (in N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide) and lyophilization. The scaffolds were physicochemically characterized through Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric Analysis, Differential Scanning Calorimetry, and mechanical (tensile) testing. In vitro experiments using Presto Blue and Alkaline Phosphatase assays were conducted to assess cellular viability and the scaffolds' ability to promote cellular proliferation and differentiation. Rheological analysis indicated shear thinning capabilities in the collagen gels. Crosslinked and lyophilized 3D-printed scaffolds were thermally stable at 37 °C and did not show signs of denaturation, although crosslinking resulted in poor mechanical strength. PB and ALP assays showed no signs of cytotoxicity as a result of crosslinking. Fibrillar collagen was successfully formulated into a colloidal gel for extrusion through a direct inkjet writing printer. 3D-printed scaffolds promoted cellular attachment and proliferation, making them a promising material for customized, patient-specific tissue regenerative applications.

Long-term effects of canagliflozin treatment on the skeleton of aged UM-HET3 mice.

Sodium glucose cotransporter-2 inhibitors (SGLT2is) promote urinary glucose excretion and decrease plasma glucose levels independent of insulin. Canagliflozin (CANA) is an SGLT2i, which is widely prescribed, to reduce cardiovascular complications, and as a second-line therapy after metformin in the treatment of type 2 diabetes mellitus. Despite the robust metabolic benefits, reductions in bone mineral density (BMD) and cortical fractures were reported for CANA-treated subjects. In collaboration with the National Institute on Aging (NIA)-sponsored Interventions Testing Program (ITP), we tested skeletal integrity of UM-HET3 mice fed control (137 mice) or CANA-containing diet (180 ppm, 156 mice) from 7 to 22 months of age. Micro-computed tomography (micro-CT) revealed that CANA treatment caused significant thinning of the femur mid-diaphyseal cortex in both male and female mice, did not affect trabecular bone architecture in the distal femur or the lumbar vertebra-5 in male mice, but was associated with thinning of the trabeculae at the distal femur in CANA-treated female mice. In male mice, CANA treatment is associated with significant reductions in cortical bone volumetric BMD by micro-CT, and by quantitative backscattered scanning electron microscopy. Raman microspectroscopy, taken at the femur mid-diaphyseal posterior cortex, showed significant reductions in the mineral/matrix ratio and an increased carbonate/phosphate ratio in CANA-treated male mice. These data were supported by thermogravimetric assay (TGA) showing significantly decreased mineral and increased carbonate content in CANA-treated male mice. Finally, the sintered remains of TGA were subjected to X-ray diffraction and showed significantly higher fraction of whitlockite, a calcium orthophosphate mineral, which has higher resorbability than hydroxyapatite. Overall, long-term CANA treatment compromised bone morphology and mineral composition of bones, which likely contribute to increased fracture risk seen with this drug.

In vivo efficacy of calcium phosphate-based synthetic-bone-mineral on bone loss resulting from estrogen and mineral deficiencies.

Osteopenia and osteoporosis affect over 40 million US adults 50 years and older. Both diseases are strongly influenced by estrogen and nutritional-mineral deficiencies. This study investigates the efficacy of orally delivered synthetic-bone-mineral (SBM), a newly developed calcium phosphate based biomaterial, on reversing bone loss induced by these two critical deficiencies. Thirty 3-month-old female rats were randomly allocated to either control-sham surgery on normal diet; or one of the four experimental groups: Sham surgery on a low mineral diet (LMD), ovariectomized (OVX) on LMD, OVX on LMD with SBM with/without fluoride (F). The rats were sacrificed after 6 months, at 9-month-old. After 6 months, although all groups lost bone mineral density relative to controls, the supplemented OVX rats showed higher bone mineral density than their unsupplemented counterparts. The 2 SBM supplemented groups improved bone loading capacity by 28.1 and 35.4% compared to the OVX LMD group. Bones from supplemented rats exhibited higher inorganic/organic ratios. The addition of F did not have a significant influence on bone loss. Our findings suggest that SBM supplement is effective in maintaining bone health and offsetting the deleterious effects of estrogen and/or mineral deficiencies on bone density, microarchitecture, and strength.

Mg substituted apatite coating from alkali conversion of acidic calcium phosphate.

In this work, two solutions were developed: the first, rich in Ca2+, PO43- ions and the second, rich in Ca2+, PO43- and Mg2+, defined as Mg-modified precursor solution. For each Mg-modified precursor solution, the concentrations of Mg2+ ions were progressively increased by 5%, 10% and 15%wt. The aims of this research were to investigate the influence of magnesium ions substitution in calcium phosphate coatings on titanium surface and to evaluate these coatings by bioactivity assay in McCoy culture medium. The obtained coatings were characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analysis, and the presence of Mg ions was confirmed by the inductively coupled plasma atomic emission spectroscopy (ICP) analysis. In vitro bioactivity assay in McCoy culture medium showed bioactivity after 14days in incubation for the HA and 10% Mg-monetite coatings. The high chemical stability of Mg-HA coatings was verified by the bioactivity assays, and no bone-like apatite deposition, characteristic of bioactivity, was observed for Mg-HA coatings, for the time period used in this study.

Effect of a dietary supplement on peri-implant bone strength in a rat model of osteoporosis.

PURPOSE: Osteoporosis contributes to impaired bone regeneration and remodeling through an imbalance of osteoblastic and osteoclastic activity, and can delay peri-implant bone formation after dental implant surgery, resulting in a prolonged treatment period. It poses several difficulties for individuals with large edentulous areas, and decreases their quality of life. Consequently, prompt postoperative placement of the final prosthesis is very important clinically. Peri-implant bone formation may be enhanced by systemic approaches, such as the use of osteoporosis supplements, to promote bone metabolism. We aimed to confirm whether intake of synthetic bone mineral (SBM), a supplement developed for osteoporosis, could effectively accelerate peri-implant bone formation in a rat model of osteoporosis. METHODS: Thirty-six 7-week-old ovariectomized female Wistar rats were randomly assigned to receive a standardized diet with or without SBM (Diet with SBM group and Diet without SBM group, respectively; n=18 for both). The rats underwent implant surgery at 9 weeks of age under general anesthesia. The main outcome measures, bone mineral density (BMD) and pull-out strength of the implant from the femur, were compared at 2 and 4 weeks after implantation using the Mann-Whitney U test. RESULTS: Pull-out strength and BMD in the Diet with SBM group were significantly greater than those in the Diet without SBM group at 2 and 4 weeks after implantation. CONCLUSIONS: This study demonstrated that SBM could be effective in accelerating peri-implant bone formation in osteoporosis.

Preservation and promotion of bone formation in the mandible as a response to a novel calcium-phosphate based biomaterial in mineral deficiency induced low bone mass male versus female rats.

Calcium and other trace mineral supplements have previously demonstrated to safely improve bone quality. We hypothesize that our novel calcium-phosphate based biomaterial (SBM) preserves and promotes mandibular bone formation in male and female rats on mineral deficient diet (MD). Sixty Sprague-Dawley rats were randomly assigned to receive one of three diets (n = 10): basic diet (BD), MD or mineral deficient diet with 2% SBM. Rats were sacrificed after 6 months. Micro-computed tomography (µCT) was used to evaluate bone volume and 3D-microarchitecture while microradiography (Faxitron) was used to measure bone mineral density from different sections of the mandible. Results showed that bone quality varied with region, gender and diet. MD reduced bone mineral density (BMD) and volume and increased porosity. SBM preserved BMD and bone mineral content (BMC) in the alveolar bone and condyle in both genders. In the alveolar crest and mandibular body, while preserving more bone in males, SBM also significantly supplemented female bone. Results indicate that mineral deficiency leads to low bone mass in skeletally immature rats, comparatively more in males. Furthermore, SBM administered as a dietary supplement was effective in preventing mandibular bone loss in all subjects. This study suggests that the SBM preparation has potential use in minimizing low peak bone mass induced by mineral deficiency and related bone loss irrespective of gender. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1622-1632, 2016.

Dental caries prevalence among a sample of African American adults in New York City.

According to available limited epidemiology studies, the prevalence of oral disease is much greater in American minorities (Blacks, Hisoanics, Asians, Native Americans) than in the majority population. The purpose of this article is to describe the oral health status and current treatment needs of a group of African-American (AA) adults in New York City. The convenience sample consisted of 951 AA adults (M = 662, F = 289) recruited through community- or faith-based institutions, and the in-house screening conducted by the Research Center for Minority Oral Health in dedicated dental clinics at the New York University College of Dentistry. The age of participants ranged from 18 to 64 years, (mean age 42, SD = 11.04). Calibrated examiners performed the clinical examinations utilizing National Institute of Dental and Craniofacial Research (NIDCR) diagnostic criteria. The DMFT, DMFS, DFS, and %D/DFS indices were obtained and results indicated the following. For the 18 to 34 age group (n = 246), the mean DMFT was 8.83, the mean DMFS was 21.36, the mean DFS was 12.10, and the mean %D/DFS was 30. For the 35 to 49 age group (n = 523), the mean DMFT was 14.03, the mean DMFS was 48.21, the mean DFS was 18.76, and the mean %D/DFS was 29. For the 50 to 64 age group (n = 182), the mean DMFT was 15.38, the mean DMFS was 64.48, the mean DFS was 17.98, and the mean %D/DFS was 29. For all age groups, the findings indicated a high prevalence of dental decay and greater number of filled surfaces compared with the United States national surveys.

Destructive periodontal diseases in minority populations.

Disparities in the prevalence and severity of destructive periodontal diseases have been reported for American minority populations and have raised the following questions. Are differences in destructive periodontal disease prevalence and severity due to genetic or other confounding variables associated with ethnicity race? Do risk factors for destructive periodontal diseases differ among American minority populations or differ from the population at large? Answers to these questions will have profound impact on the direction of future research and the allocation of resources to address disparities in destructive periodontal diseases in American minority populations. Risk assessment studies that examined a set of clinical, demographic, immunologic, and microbiologic parameters of Asian Americans, African Americans, and Hispanic Americans resident in the greater New York City region suggest that occupational status, monitored as a surrogate variable for socioeconomic status, may be a more robust risk factor than ethnicity/race for destructive periodontal diseases in these populations.

Engineering endochondral bone: in vivo studies.

The use of biomaterials to replace lost bone has been a common practice for decades. More recently, the demands for bone repair and regeneration have pushed research into the use of cultured cells and growth factors in association with these materials. Here we report a novel approach to engineer new bone using a transient cartilage scaffold to induce endochondral ossification. Chondrocyte/chitosan scaffolds (both a transient cartilage scaffold-experimental-and a permanent cartilage scaffold-control) were prepared and implanted subcutaneously in nude mice. Bone formation was evaluated over a period of 5 months. Mineralization was assessed by Faxitron, micro computed tomography, backscatter electrons, and Fourier transform infrared spectroscopy analyses. Histological analysis provided further information on tissue changes in and around the implanted scaffolds. The deposition of ectopic bone was detected in the surface of the experimental implants as early as 1 month after implantation. After 3 months, bone trabeculae and bone marrow cavities were formed inside the scaffolds. The bone deposited was similar to the bone of the mice vertebra. Interestingly, no bone formation was observed in control implants. In conclusion, an engineered transient cartilage template carries all the signals necessary to induce endochondral bone formation in vivo.

Progression of destructive periodontal diseases in three urban minority populations: role of clinical and demographic factors.

BACKGROUND, AIMS: Differences in prevalence, severity and risk factors for destructive periodontal diseases have been reported for ethnic/racial groups. However, it is not certain whether this disparity is due to ethnicity/race or factors associated with ethnicity/race. Therefore, the present study addressed whether the rates of disease progression and clinical and demographic factors associated with disease progression varied among three ethnic/racial groups. METHODS: The study population consisted of 53 Asian-, 69 African- and 62 Hispanic-Americans. Clinical measurements included probing depth, attachment level, gingival erythema, bleeding upon probing, suppuration and plaque. Disease progression was defined as a > 2 mm loss of attachment 2 months post baseline. The demographic variables examined included occupational status, report of a private dentist, years resident in the United States and smoking history. RESULTS: The rate of attachment loss for the entire population was 0.04 mm or 0.24 mm/year. No significant differences were found among the three ethnic/racial groups. Variables associated with subsequent attachment loss for the entire population were age, male gender, mean whole-mouth plaque, erythema, bleeding upon probing, suppuration, attachment loss and probing depth, and belonging to the "unskilled" occupational group. No differences in risk profiles were found among the 3 ethnic/racial groups. Using stepwise logistic regression analysis, a model was developed to relate the clinical and demographic variables examined with subsequent attachment loss. The model indicated that prior attachment loss, gingival erythema, suppuration, being a current smoker and belonging to the "unskilled" occupational group conferred high risk of > 1 site of attachment loss of > 2 mm. CONCLUSIONS: The results of this study suggest that variables associated with ethnicity/race, such as occupational status, are largely responsible for the observed disparity in destructive periodontal disease progression in these populations.