Dataset Information

Micropatterned Scaffolds with Immobilized Growth Factor Genes Regenerate Bone and Periodontal Ligament-Like Tissues.

ABSTRACT: Periodontal disease destroys supporting structures of teeth. However, tissue engineering strategies offer potential to enhance regeneration. Here, the strategies of patterned topography, spatiotemporally controlled growth factor gene delivery, and cell-based therapy to repair bone-periodontal ligament (PDL) interfaces are combined. Micropatterned scaffolds are fabricated for the ligament regions using polycaprolactone (PCL)/polylactic-co-glycolic acid and combined with amorphous PCL scaffolds for the bone region. Scaffolds are modified using chemical vapor deposition, followed by spatially controlled immobilization of vectors encoding either platelet-derived growth factor-BB or bone morphogenetic protein-7, respectively. The scaffolds are seeded with human cells and delivered to large alveolar bone defects in athymic rats. The effects of dual and single gene delivery with and without micropatterning are assessed after 3, 6, and 9 weeks. Gene delivery results in greater bone formation at three weeks. Micropatterning results in regenerated ligamentous tissues similar to native PDL. The combination results in more mature expression of collagen III and periostin, and with elastic moduli of regenerated tissues that are statistically indistinguishable from those of native tissue, while controls are less stiff than native tissues. Thus, controlled scaffold microtopography combined with localized growth factor gene delivery improves the regeneration of periodontal bone-PDL interfaces.

SUBMITTER: Pilipchuk SP

PROVIDER: S-EPMC6394861 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Micropatterned Scaffolds with Immobilized Growth Factor Genes Regenerate Bone and Periodontal Ligament-Like Tissues.

Pilipchuk Sophia P SP Fretwurst Tobias T Yu Ning N Larsson Lena L Kavanagh Nolan M NM Asa'ad Farah F Cheng Kenneth C K KCK Lahann Joerg J Giannobile William V WV

Advanced healthcare materials 20181019 22

Periodontal disease destroys supporting structures of teeth. However, tissue engineering strategies offer potential to enhance regeneration. Here, the strategies of patterned topography, spatiotemporally controlled growth factor gene delivery, and cell-based therapy to repair bone-periodontal ligament (PDL) interfaces are combined. Micropatterned scaffolds are fabricated for the ligament regions using polycaprolactone (PCL)/polylactic-co-glycolic acid and combined with amorphous PCL scaffolds fo ...[more]

PMID: 30338658

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Project description:The structural and functional integrity of bone-periodontal ligament (PDL)-cementum complex stems from the load-bearing attachment sites (entheses) between soft (PDL) and hard (bone, cementum) tissues. These attachment sites are responsible for the maintenance of a bone-PDL-cementum complex biomechanical function. The objective was to investigate changes in spatiotemporal expression of key biomolecules in developing and functionally active entheses.Multilabeling technique was performed on hemimandibles of 3 wk and 3 mo-old scleraxis-GFP transgenic mice for CD146, CD31, NG2, osterix and bone sialoprotein. Regions of dominant stretch within the PDL were evaluated by identifying directionality of collagen fibrils, PDL fibroblasts and PDL cell cytoskeleton.CD146+ cells adjacent to CD31+ vasculature were identified at PDL-bone enthesis. NG2+ cells were located at coronal bone-PDL and apical cementum-PDL entheses in the 3-wk-old group, but at 3 mo, NG2 was positive at the entheses of the apical region and alveolar crest. NG2 and osterix were colocalized at the osteoid and cementoid regions of the PDL-bone and PDL-cementum entheses. Bone sialoprotein was prominent at the apical region of 3-wk-old mice. The directionality of collagen fibers, fibroblasts and their cytoskeleton overlapped, except in the apical region of 3 wk.Colocalization of biomolecules at zones of the PDL adjacent to attachment sites may be essential for the formation of precementum and osteoid interfaces at a load-bearing bone-PDL-tooth fibrous joint. Biophysical cues resulting from development and function can regulate recruitment and differentiation of stem cells potentially from a vascular origin toward osteo- and cemento-blastic lineages at the PDL-bone and PDL-cementum entheses. Investigating the coupled effect of biophysical and biochemical stimuli leading to cell differentiation at the functional attachment sites is critical for developing regeneration strategies to enable functional reconstruction of the periodontal complex.

Project description:BACKGROUND:Autologous bone grafts remain a standard of care for the reconstruction of large bony defects, but limitations persist. The authors explored the bone regenerative capacity of customized, three-dimensionally printed bioactive ceramic scaffolds with dipyridamole, an adenosine A2A receptor indirect agonist known to enhance bone formation. METHODS:Critical-size bony defects (10-mm height, 10-mm length, full-thickness) were created at the mandibular rami of rabbits (n = 15). Defects were replaced by a custom-to-defect, three-dimensionally printed bioactive ceramic scaffold composed of ?-tricalcium phosphate. Scaffolds were uncoated (control), collagen-coated, or immersed in 100 ?M dipyridamole. At 8 weeks, animals were euthanized and the rami retrieved. Bone growth was assessed exclusively within scaffold pores, and evaluated by micro-computed tomography/advanced reconstruction software. Micro-computed tomographic quantification was calculated. Nondecalcified histology was performed. A general linear mixed model was performed to compare group means and 95 percent confidence intervals. RESULTS:Qualitative analysis did not show an inflammatory response. The control and collagen groups (12.3 ± 8.3 percent and 6.9 ± 8.3 percent bone occupancy of free space, respectively) had less bone growth, whereas the most bone growth was in the dipyridamole group (26.9 ± 10.7 percent); the difference was statistically significant (dipyridamole versus control, p < 0.03; dipyridamole versus collagen, p < 0.01 ). There was significantly more residual scaffold material for the collagen group relative to the dipyridamole group (p < 0.015), whereas the control group presented intermediate values (nonsignificant relative to both collagen and dipyridamole). Highly cellular and vascularized intramembranous-like bone healing was observed in all groups. CONCLUSION:Dipyridamole significantly increased the three-dimensionally printed bioactive ceramic scaffold's ability to regenerate bone in a thin bone defect environment.

Project description:This study investigates bone-tooth association under compression to identify strain amplified sites within the bone-periodontal ligament (PDL)-tooth fibrous joint. Our results indicate that the biomechanical response of the joint is due to a combinatorial response of the constitutive properties of organic, inorganic, and fluid components. Second maxillary molars within intact maxillae (N=8) of 5-month-old rats were loaded with a ?-XCT-compatible in situ loading device at various permutations of displacement rates (0.2, 0.5, 1.0, 1.5, 2.0 mm/min) and peak reactionary load responses (5, 10, 15, 20 N). Results indicated a nonlinear biomechanical response of the joint, in which the observed reactionary load rates were directly proportional to displacement rates (velocities). No significant differences in peak reactionary load rates at a displacement rate of 0.2mm/min were observed. However, for displacement rates greater than 0.2mm/min, an increasing trend in reactionary rate was observed for every peak reactionary load with significant increases at 2.0mm/min. Regardless of displacement rates, two distinct behaviors were identified with stiffness (S) and reactionary load rate (LR) values at a peak load of 5 N (S(5 N)=290-523 N/mm) being significantly lower than those at 10 N (LR(5 N)=1-10 N/s) and higher (S(10 N-20 N)=380-684 N/mm; LR(10 N-20 N)=1-19 N/s). Digital image correlation revealed the possibility of a screw-like motion of the tooth into the PDL-space, i.e., predominant vertical displacement of 35 ?m at 5 N, followed by a slight increase to 40 ?m at 10 N and 50 ?m at 20 N of the tooth and potential tooth rotation at loads above 10 N. Narrowed and widened PDL spaces as a result of tooth displacement indicated areas of increased apparent strains within the complex. We propose that such highly strained regions are "hot spots" that can potentiate local tissue adaptation under physiological loading and adverse tissue adaptation under pathological loading conditions.

Dataset Information

Micropatterned Scaffolds with Immobilized Growth Factor Genes Regenerate Bone and Periodontal Ligament-Like Tissues.

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Micropatterned Scaffolds with Immobilized Growth Factor Genes Regenerate Bone and Periodontal Ligament-Like Tissues.

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