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International Journal of Molecular... Mar 2023The repair of orthopedic and maxillofacial defects in modern medicine currently relies heavily on the use of autograft, allograft, void fillers, or other structural...
The repair of orthopedic and maxillofacial defects in modern medicine currently relies heavily on the use of autograft, allograft, void fillers, or other structural material composites. This study examines the in vitro osteo regenerative potential of polycaprolactone (PCL) tissue scaffolding, fabricated via a three-dimensional (3D) additive manufacturing technology, i.e., a pneumatic micro extrusion (PME) process. The objectives of this study were: (i) To examine the innate osteoinductive and osteoconductive potential of 3D-printed PCL tissue scaffolding and (ii) To perform a direct in vitro comparison of 3D-printed PCL scaffolding with allograft Allowash cancellous bone cubes with regards to cell-scaffold interactions and biocompatibility with three primary human bone marrow (hBM) stem cell lines. This study specifically examined cell survival, cell integration, intra-scaffold cell proliferation, and differentiation of progenitor cells to investigate the potential of 3D-printed PCL scaffolds as an alternative to allograft bone material for the repair of orthopedic injuries. We found that mechanically robust PCL bone scaffolds can be fabricated via the PME process and the resulting material did not elicit detectable cytotoxicity. When the widely used osteogenic model SAOS-2 was cultured in PCL extract medium, no detectable effect was observed on cell viability or proliferation with multiple test groups showing viability ranges of 92.2% to 100% relative to a control group with a standard deviation of ±10%. In addition, we found that the honeycomb infill pattern of the 3D-printed PCL scaffold allowed for superior mesenchymal stem-cell integration, proliferation, and biomass increase. When healthy and active primary hBM cell lines, having documented in vitro growth rates with doubling times of 23.9, 24.67, and 30.94 h, were cultured directly into 3D-printed PCL scaffolds, impressive biomass increase values were observed. It was found that the PCL scaffolding material allowed for biomass increase values of 17.17%, 17.14%, and 18.18%, compared to values of 4.29% for allograph material cultured under identical parameters. It was also found that the honeycomb scaffold infill pattern was superior to the cubic and rectangular matrix structures, and provided a superior microenvironment for osteogenic and hematopoietic progenitor cell activity and auto-differentiation of primary hBM stem cells. Histological and immunohistochemical studies performed in this work confirmed the regenerative potential of PCL matrices in the orthopedic setting by displaying the integration, self-organization, and auto-differentiation of hBM progenitor cells within the matrix. Differentiation products including mineralization, self-organizing "proto-osteon" structures, and in vitro erythropoiesis were observed in conjunction with the documented expression of expected bone marrow differentiative markers including CD-99 (>70%), CD-71 (>60%), and CD-61 (>5%). All of the studies were conducted without the addition of any exogenous chemical or hormonal stimulation and exclusively utilized the abiotic and inert material polycaprolactone; setting this work apart from the vast majority of contemporary investigations into synthetic bone scaffold fabrication In summary, this study demonstrates the unique clinical potential of 3D-printed PCL scaffolds for stem cell expansion and incorporation into advanced microstructures created via PME manufacturing to generate a physiologically inert temporary bony defect graft with significant autograft features for enhanced end-stage healing.
Topics: Humans; Bone Marrow Cells; Caproates; Osteogenesis; Polyesters; Printing, Three-Dimensional; Tissue Engineering; Tissue Scaffolds; Mesenchymal Stem Cells
PubMed: 36902373
DOI: 10.3390/ijms24054940 -
Acta Biomaterialia May 2023Bone fragility is a profound complication of type 1 diabetes mellitus (T1DM), increasing patient morbidity. Within the mineralized bone matrix, osteocytes build a...
Bone fragility is a profound complication of type 1 diabetes mellitus (T1DM), increasing patient morbidity. Within the mineralized bone matrix, osteocytes build a mechanosensitive network that orchestrates bone remodeling; thus, osteocyte viability is crucial for maintaining bone homeostasis. In human cortical bone specimens from individuals with T1DM, we found signs of accelerated osteocyte apoptosis and local mineralization of osteocyte lacunae (micropetrosis) compared with samples from age-matched controls. Such morphological changes were seen in the relatively young osteonal bone matrix on the periosteal side, and micropetrosis coincided with microdamage accumulation, implying that T1DM drives local skeletal aging and thereby impairs the biomechanical competence of the bone tissue. The consequent dysfunction of the osteocyte network hampers bone remodeling and decreases bone repair mechanisms, potentially contributing to the enhanced fracture risk seen in individuals with T1DM. STATEMENT OF SIGNIFICANCE: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease that causes hyperglycemia. Increased bone fragility is one of the complications associated with T1DM. Our latest study on T1DM-affected human cortical bone identified the viability of osteocytes, the primary bone cells, as a potentially critical factor in T1DM-bone disease. We linked T1DM with increased osteocyte apoptosis and local accumulation of mineralized lacunar spaces and microdamage. Such structural changes in bone tissue suggest that T1DM speeds up the adverse effects of aging, leading to the premature death of osteocytes and potentially contributing to diabetes-related bone fragility.
Topics: Humans; Osteocytes; Diabetes Mellitus, Type 1; Aging; Bone and Bones; Apoptosis
PubMed: 36878337
DOI: 10.1016/j.actbio.2023.02.037 -
IUCrJ Mar 2023Bone is a complex, biological tissue made up primarily of collagen fibrils and biomineral nanoparticles. The importance of hierarchical organization in bone was realized...
Bone is a complex, biological tissue made up primarily of collagen fibrils and biomineral nanoparticles. The importance of hierarchical organization in bone was realized early on, but the actual interplay between structural features and the properties on the nanostructural and crystallographic level is still a matter of intense discussion. Bone is the only mineralized tissue that can be remodeled and, at the start of the formation of new bone during this process, a structure called a cement line is formed on which regular bone grows. Here, the orientational relationship of nanostructural and crystallographic constituents as well as the structural properties of both nanostructural and crystallographic constituents around cement lines and the Haversian system in human lamellar bone are investigated. A combination of small- and wide-angle X-ray scattering tensor tomography is employed together with diffraction tomography and synchrotron computed tomography to generate a multi-modal image of the sample. This work shows that the mineral properties vary as a function of the distance to the Haversian canal and, importantly, shows that the cement line has differing mineral properties from the surrounding lamellar bone, in particular with respect to crystallite size and degree of orientation. Cement lines make up a significant portion of the bone matrix despite their small size, hence the reported findings on an altered mineral structure, together with the spatial modulation around the Haversian canal, have implications for the formation and mechanics of bone.
Topics: Humans; Haversian System; Collagen; Bone and Bones; Bone Matrix; Minerals
PubMed: 36786504
DOI: 10.1107/S2052252523000866 -
Nutrients Jan 2023Short-term animal experiments and association studies in humans have shown that cola intake may have a detrimental impact on bone mineral density (BMD); however, other...
Short-term animal experiments and association studies in humans have shown that cola intake may have a detrimental impact on bone mineral density (BMD); however, other bone parameters have not been investigated. This study examined the effects of long-term cola consumption on the femoral bone microstructure using adult mice ( = 32) as an animal model, which were divided into water and cola groups depending on whether they received water or cola along with a standard rodent diet for 6 months. Micro-computed tomography revealed that cola intake did not significantly affect all measured parameters characterizing trabecular bone mass and microarchitecture, as well as cortical microarchitecture and geometry in both sexes, although a slight deterioration of these parameters was noted. Cola consumption also resulted in a slightly, statistically insignificant worsening of bone mechanical properties. In contrast to female mice, males receiving cola had a lower area of primary osteons' vascular canals. Nevertheless, long-term cola intake did not cause evident pathological alterations in the femur of adult mice, possibly due to a balanced diet and no restriction of physical activity. Therefore, the adverse effects of cola consumption on BMD, the only bone parameter studied so far, may be caused by other risk and lifestyle factors.
Topics: Adult; Humans; Male; Mice; Animals; Female; Cola; X-Ray Microtomography; Bone and Bones; Bone Density; Femur
PubMed: 36771291
DOI: 10.3390/nu15030583 -
Nigerian Journal of Clinical Practice Jan 2023The aim of this study was to evaluate radiographically the prevalence of mandibular nutrient canals (NCs) in patients with/without periodontal bone loss with aging and...
BACKGROUND AND AIM
The aim of this study was to evaluate radiographically the prevalence of mandibular nutrient canals (NCs) in patients with/without periodontal bone loss with aging and to correlate the number of NCs with the severity of bone loss using cone-beam-computed tomography (CBCT).
PATIENTS AND METHODS
CBCT examinations of 208 patients were evaluated retrospectively of all patients, 114 had periodontal bone loss, whereas 94 patients were control subjects. Alveolar bone loss investigations were performed according to the Progressive Rate Index.
RESULTS
NCs were observed in 55% of the control group and 86% of the periodontitis patients. NCs were more prevalent in the elderly age group with periodontal bone loss. In the study group, the NCs were statistically more frequent than in the control subjects (P > 0.05).
CONCLUSION
Statistical analysis showed a significant difference between the age groups and the prevalence of NCs increased in patients with periodontal alveolar bone loss with aging (P < 0.05).
Topics: Humans; Aged; Alveolar Bone Loss; Retrospective Studies; Haversian System; Cone-Beam Computed Tomography; Periodontal Diseases; Mandible
PubMed: 36751825
DOI: 10.4103/njcp.njcp_210_22 -
Annals of Anatomy = Anatomischer... Apr 2023There is a genetic component to the minimum effective strain (MES)-a threshold which determines when bone will adapt to function-which suggests ancestry should play a...
BACKGROUND
There is a genetic component to the minimum effective strain (MES)-a threshold which determines when bone will adapt to function-which suggests ancestry should play a role in bone (re)modelling. Further elucidating this is difficult in living human populations because of the high global genetic admixture. We examined femora from an anthropological skeletal assemblage (Mán Bạc, Vietnam) representing distinct ancestral groups. We tested whether femur morphological and histological markers of modelling and remodelling differed between ancestries despite their similar lifestyles.
METHODS
Static histomorphometry data collected from subperiosteal cortical bone of the femoral midshaft, and gross morphometric measures of femur robusticity, were studied in 17 individuals from the Mán Bạc collection dated to 1906-1523 cal. BC. This assemblage represents agricultural migrants with affinity to East Asian groups, who integrated with the local hunter-gatherers with affinity to Australo-Papuan groups during the mid-Holocene. Femur robusticity and histology data were compared between groups of 'Migrant' (n = 8), 'Admixed' (n = 4), and 'Local' (n = 5).
RESULTS
Local individuals had more robust femoral diaphyses with greater secondary osteon densities, and relatively large secondary osteon and Haversian canal parameters than the migrants. The Migrant group showed gracile femoral shafts with the least dense bone made up of small secondary osteons and Haversian canals. The Admixed individuals fell between the Migrant and Local categories in terms of their femoral data. However, we also found that measures of how densely bone is remodelled per unit area were in a tight range across all three ancestries.
CONCLUSIONS
Bone modelling and remodelling markers varied with ancestral histories in our sample. This suggests that there is an ancestry related predisposition to bone optimising its metabolic expenditure likely in relation to the MES. Our results stress the need to incorporate population genetic history into hierarchical bone analyses. Understanding ancestry effects on bone morphology has implications for interpreting biomechanical loading history in past and modern human populations.
Topics: Humans; Vietnam; Femur; Lower Extremity; Haversian System; Histological Techniques
PubMed: 36696927
DOI: 10.1016/j.aanat.2023.152054 -
Bioengineering & Translational Medicine Jan 2023Although numerous organ-on-a-chips have been developed, bone-on-a-chip platforms have rarely been reported because of the high complexity of the bone microenvironment....
Although numerous organ-on-a-chips have been developed, bone-on-a-chip platforms have rarely been reported because of the high complexity of the bone microenvironment. With an increase in the elderly population, a high-risk group for bone-related diseases such as osteoporosis, it is essential to develop a precise bone-mimicking model for efficient drug screening and accurate evaluation in preclinical studies. Here, we developed a high-throughput biomimetic bone-on-a-chip platform combined with an artificial intelligence (AI)-based image analysis system. To recapitulate the key aspects of natural bone microenvironment, mouse osteocytes (IDG-SW3) and osteoblasts (MC3T3-E1) were cocultured within the osteoblast-derived decellularized extracellular matrix (OB-dECM) built in a well plate-based three-dimensional gel unit. This platform spatiotemporally and configurationally mimics the characteristics of the structural bone unit, known as the osteon. Combinations of native and bioactive ingredients obtained from the OB-dECM and coculture of two types of bone cells synergistically enhanced osteogenic functions such as osteocyte differentiation and osteoblast maturation. This platform provides a uniform and transparent imaging window that facilitates the observation of cell-cell interactions and features high-throughput bone units in a well plate that is compatible with a high-content screening system, enabling fast and easy drug tests. The drug efficacy of anti-SOST antibody, which is a newly developed osteoporosis drug for bone formation, was tested via β-catenin translocation analysis, and the performance of the platform was evaluated using AI-based deep learning analysis. This platform could be a cutting-edge translational tool for bone-related diseases and an efficient alternative to bone models for the development of promising drugs.
PubMed: 36684077
DOI: 10.1002/btm2.10313 -
Life (Basel, Switzerland) Dec 2022Periodontal regeneration through the employment of bone substitutes has become a feasible strategy in animal and clinical studies. In this regard, we aimed to compare...
Periodontal regeneration through the employment of bone substitutes has become a feasible strategy in animal and clinical studies. In this regard, we aimed to compare the periodontal ligament stem cell behavior in the vicinity of various bone grafting substitutes. Three types of popular bone substitutes, including allografts (Regen), xenografts (Cerabone), and alloplasts (Osteon) were studied in this experimental survey. The cellular attachment was assessed after four hours using the MTS assay and SEM imaging. In addition, cellular proliferation was investigated after 1, 3, 5, and 7 days through MTS assay. Osteogenesis was studied after 21 days of cell culture in a differentiation medium (DM+) and a normal medium (DM-), by employing real-time PCR and alizarin red staining. The highest cellular attachment was seen in the xenograft group with a significant difference in comparison to the other grafting materials. Despite the relatively low primary attachment of cells to allografts, the allograft group showed the highest total proliferation rate, while the lowest proliferation capacity was found in the alloplast group. Osteogenesis fount to be accelerated mostly by xenografts in both mediums (DM+ and DM-) after 3 weeks, while alloplasts showed the lowest osteogenesis. This study revealed that the type of bone substitutes used in regenerative treatments can affect cellular behavior and as a whole allografts and xenografts showed better results.
PubMed: 36676038
DOI: 10.3390/life13010089 -
The International Journal of... 2023This study evaluated bone behavior during dynamic osseointegration. A total of 12 implants were placed in sheep tibia and analyzed at 15, 30, 60, and 90 days....
This study evaluated bone behavior during dynamic osseointegration. A total of 12 implants were placed in sheep tibia and analyzed at 15, 30, 60, and 90 days. Quantitative and qualitative bone behaviors were evaluated with histologic, histomorphometric, Alizarin Red S, and SEM-EDX (scanning electron microscopy with energy-dispersive x-ray spectroscopy) analysis. Twenty microanalyses were performed in chambers 1, 3, and 5 (a chamber is the distinctive space/bone volume between two coils of the implant screw) in distinctive zones: the titanium-bone interface (zone A), the middle chamber-bone front (zone B), the bone-surgical threading interface (zone C), and native bone (zone D; used as a control). The dynamic osseointegration index (DOI) and bone quality index (BQI) with calcium/phosphorus (Ca/P) content were detected to evaluate the osseointegration quality, bone-to-implant contact (BIC), and bone density around implants. At 15 days, initial bone formation with osteoid matrix deposition and different color intensities were observed (means: BIC = 23.3% ± 3.9%; DOI = 1.55). SEM-EDX analysis showed low mineralized bone/bone marrow with a very low Ca/P mean value. At 30 days, high new bone deposition with higher color intensity in the crestal portion was recorded (BIC = 77.3% ± 0.4%; DOI = 2.58). At 90 days, tight BIC to the middle and apical implant portions were detected, as well as several osteon structures in the crestal portion (BIC = 86.4% ± 0.6%; DOI = 0.96). During all observed time periods, the BQI showed 25% more Ca/P in zone A. Greater maturation degree and lower BQI were seen at zone A compared to the other zones. After 15 and 30 days, zones B and C (except for P in zone B) showed BQIs slightly over 50% and around 75%, respectively, confirming a progressively higher degree of bone maturation that proceeds with the osseointegration process. After 90 days, the BQI values of zones B and C (greater than 70% in zone B and around 90% in zone C) confirmed the bone mineralization and maturation process and an acceleration of implant osseointegration, while a lower BQI value (25%) was recorded in zone A. This study shows osseointegration as a variable dynamic process with a higher bone deposition in contact with the implant surface during the early phase, while in the active and later osseointegration times, the bone quality maturation showed higher values only "at distance" (growth of native bone to the implant surface, observed later in the osseointegration process). After 3 months (before loading), the BQI evaluation was lower (25%) in zone A, confirming that the healing and maturation process of the bone cannot be considered complete.
Topics: Animals; Sheep; Osseointegration; Dental Implants; Surface Properties; Bone Density; Titanium; Biological Products
PubMed: 36661877
DOI: 10.11607/prd.6139 -
Journal of Advanced Research Dec 2023The bone ingrowth depth in the porous scaffolds is greatly affected by the structural design, notably the pore size, pore geometry, and the pore distribution. To enhance...
INTRODUCTION
The bone ingrowth depth in the porous scaffolds is greatly affected by the structural design, notably the pore size, pore geometry, and the pore distribution. To enhance the bone regeneration capability of scaffolds, the bionic design can be regarded as a potential solution.
OBJECTIVES
We proposed a Haversian system-like gradient structure based on the triply periodic minimal surface architectures with pore size varying from the edge to the center. And its effects in promoting bone regeneration were evaluated in the study.
METHODS
The gradient scaffold was designed using the triply periodic minimal surface architectures. The mechanical properties were analyzed by the finite element simulation and confirmed using the universal machine. The fluid characteristics were calculated by the computational fluid dynamics analysis. The bone regeneration process was simulated using a in silico computational model containing the main biological, physical, and chemical variation during the bone growth process. Finally, the in vitro and in vivo studies were carried out to verify the actual osteogenic effect.
RESULTS
Compared to the uniform scaffold, the biomimetic gradient scaffold demonstrated better performance in stress conduction and reduced stress shielding effects. The fluid features were appropriate for cell migration and flow diffusion, and the permeability was in the same order of magnitude with the natural bone. The bone ingrowth simulation exhibited improved angiogenesis and bone regeneration. Higher expression of the osteogenesis-related genes, higher alkaline phosphatase activity, and increased mineralization could be observed on the gradient scaffold in the in vitro study. The 12-week in vivo study proved that the gradient scaffold had deeper bone inserting depth and a more stable bone-scaffold interface.
CONCLUSION
The Haversian system-like gradient structure can effectively promote the bone regeneration. This structural design can be used as a new solution for the clinical application of prosthesis design.
Topics: Tissue Scaffolds; Porosity; Haversian System; Osteogenesis; Bone Regeneration
PubMed: 36632888
DOI: 10.1016/j.jare.2023.01.004