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Tissue Engineering. Part B, Reviews Apr 2022Bone is composed of dense and solid cortical bone and honeycomb-like trabecular bone. Although cortical bone provides the majority of mechanical strength for a bone,... (Review)
Review
Bone is composed of dense and solid cortical bone and honeycomb-like trabecular bone. Although cortical bone provides the majority of mechanical strength for a bone, there are few studies focusing on cortical bone repair or regeneration. Osteons (the Haversian system) form structural and functional units of cortical bone. In recent years, emerging evidences have shown that the osteon structure (including osteocytes, lamellae, lacunocanalicular network, and Haversian canals) plays critical roles in bone mechanics and turnover. Therefore, reconstruction of the osteon structure is crucial for cortical bone regeneration. This article provides a systematic summary of recent advances in osteons, including the structure, function, turnover, and regenerative strategies. First, the hierarchical structure of osteons is illustrated and the critical functions of osteons in bone dynamics are introduced. Next, the modeling and remodeling processes of osteons at a cellular level and the turnover of osteons in response to mechanical loading and aging are emphasized. Furthermore, several bioengineering approaches that were recently developed to recapitulate the osteon structure are highlighted. Impact statement This review provides a comprehensive summary of recent advances in osteons, especially the roles in bone formation, remodeling, and regeneration. Besides introducing the hierarchical structure and critical functions of osteons, we elucidate the modeling and remodeling of osteons at a cellular level. Specifically, we highlight the bioengineering approaches that were recently developed to mimic the hierarchical structure of osteons. We expect that this review will provide informative insights and attract increasing attentions in orthopedic community, shedding light on cortical bone regeneration in the future.
Topics: Bone Regeneration; Bone and Bones; Haversian System; Humans; Osteocytes; Osteogenesis
PubMed: 33487116
DOI: 10.1089/ten.TEB.2020.0322 -
Anatomical Record (Hoboken, N.J. : 2007) Jun 2022Histomorphometric analysis of human cortical bone has documented the occurrence of secondary osteon variants. These include drifting osteons which form tails as they...
Histomorphometric analysis of human cortical bone has documented the occurrence of secondary osteon variants. These include drifting osteons which form tails as they move erratically through the cortex and Type II osteons which show partial resorption and redeposition within the cement line of the osteon. Little is known about the biological significance of these variants. Prior studies suggested correlations with age, biomechanics, diet, and mineral homeostasis. No study has yet tested for osteon variant associations with static measures of bone remodeling. In this study, thin sections (n = 112) of the posterior femur representing a late English Medieval adult human osteological collection, subdivided by age, sex, and socio-economic status, were examined to determine whether remodeling indicators reconstructed from osteon parameters (area, diameter, area ratios) and densities differed between categories of presence or absence of Type II and drifting osteon variants. Of the 112 sections, 33 presented with Type II osteons, and 38 had drifting osteons. Sporadic statistically significant results were identified. Haversian canal:osteon area ratio differed (p = 0.017) with Type II osteon presence, Type II osteons were more prevalent in males than females (p = 0.048), and drifting osteons were associated with smaller osteon (p = 0.049) and Haversian canal area (p = 0.05). These results may be explained through some biological (sex) and social (status) processes such as a period of physiological recovery (e.g., following lactation, malnutrition). However, the general lack of consistent relationships between osteon variants and remodeling indicators suggests they occur as a result of natural variation.
Topics: Adult; Bone Remodeling; Bone and Bones; Cortical Bone; Female; Femur; Haversian System; Humans; Male
PubMed: 33890727
DOI: 10.1002/ar.24646 -
Micron (Oxford, England : 1993) Jan 2021Haversian systems result from bone remodeling, and show variation in size and shape among differing ages, body weights, mechanical environments, and species. While...
OBJECTIVES
Haversian systems result from bone remodeling, and show variation in size and shape among differing ages, body weights, mechanical environments, and species. While variables such as osteon circularity (On.Cr.) are generally studied in single transverse cross-sections, little is known about On.Cr. variation along an osteon's length, investigated here, in order to strengthen our understanding of bone microstructure.
MATERIALS AND METHODS
Up to 875 measurements of On.Cr. were generated for 41 osteonal segments from the proximal anterior diaphysis of femoral human cortical bone of three adult male samples (ages 46, 62, 74). We employed four hypotheses to investigate On.Cr. variability, in cross-section and longitudinally. H1: There is no difference in On.Cr. among osteons comprising single cross-sections, H2: There is no difference in On.Cr. among individuals when single cross-sections are compared, H3: There is no difference in On.Cr. among measurements taken from an osteon along the longitudinal axis, and H4: There is no discernable pattern in an osteon's deviation from circularity.
RESULTS
Quantitative analysis of single cross-sections revealed relatively consistent On.Cr. measurements within individual cross-sections and among individuals, supporting both, H1 and H2. Along individual osteonal segments, substantial degrees of dispersion from central tendencies were observed in 27 out of 41 analyzed osteons (despite relatively low overall standard deviations and interquartile ranges), leading to a rejection of H3. Qualitative characterization of morphological deviation from a "typical" circularity suggests a patterned deviation, leading also to a rejection of H4.
DISCUSSION
On.Cr. variation is discussed in the context of both, phenomena intrinsic to a given osteon (including repetitive, small perturbations at roughly 45 μm intervals), and extrinsic (including shared reversal sheaths, osteonal branching, transverse connections, and osteonal repathing). Interesting associations between On.Cr. and other characteristics of the local Haversian network emphasize the role of Haversian systems as integrated parts of a greater morphological complex.
Topics: Aged; Bone Remodeling; Cortical Bone; Haversian System; Humans; Male; Middle Aged; X-Ray Microtomography
PubMed: 33099207
DOI: 10.1016/j.micron.2020.102955 -
Biofabrication Mar 2019Bone tissue engineers are facing a daunting challenge when attempting to fabricate bigger constructs intended for use in the treatment of large bone defects, which is...
Bone tissue engineers are facing a daunting challenge when attempting to fabricate bigger constructs intended for use in the treatment of large bone defects, which is the vascularization of the graft. Cell-based approaches and, in particular, the use of in vitro coculture of human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs) has been one of the most explored options. We present in this paper an alternative method to mimic the spatial pattern of HUVECs and hMSCs found in native osteons based on the use of extrusion-based 3D bioprinting (3DP). We developed a 3DP biphasic osteon-like scaffold, containing two separate osteogenic and vasculogenic cell populations encapsulated in a fibrin bioink in order to improve neovascularization. To this end, we optimized the fibrin bioink to improve the resolution of printed strands and ensure a reproducible printing process; the influence of printing parameters on extruded strand diameter and cell survival was also investigated. The mechanical strength of the construct was improved by co-printing the fibrin bioink along a supporting PCL carrier scaffold. Compressive mechanical testing showed improved mechanical properties with an average compressive modulus of 131 ± 23 MPa, which falls in the range of cortical bone. HUVEC and hMSC laden fibrin hydrogels were printed in osteon-like patterns and cultured in vitro. A significant increase in gene expression of angiogenic markers was observed for the biomimetic scaffolds. Finally, biphasic scaffolds were implanted subcutaneously in rats. Histological analysis of explanted scaffolds showed a significant increase in the number of blood vessels per area in the 3D printed osteon-like scaffolds. The utilization of these scaffolds in constructing biomimetic osteons for bone regeneration demonstrated a promising capacity to improve neovascularization of the construct. These results indicates that proper cell orientation and scaffold design could play a critical role in neovascularization.
Topics: Animals; Bioprinting; Cattle; Cell Line; Fibrin; Haversian System; Human Umbilical Vein Endothelial Cells; Humans; Ink; Mesenchymal Stem Cells; Mice; Neovascularization, Physiologic; Rats, Sprague-Dawley; Swine; Tissue Scaffolds
PubMed: 30769337
DOI: 10.1088/1758-5090/ab078a -
Small (Weinheim An Der Bergstrasse,... Mar 2022Nature creates fascinating self-organized spatiotemporal patterns through the delicate control of reaction-diffusion dynamics. As the primary unit of cortical bone,...
Nature creates fascinating self-organized spatiotemporal patterns through the delicate control of reaction-diffusion dynamics. As the primary unit of cortical bone, osteon has concentric lamellar architecture, which plays a crucial role in the mechanical and physiological functions of bone. However, it remains a great challenge to fabricate the osteon-like structure in a natural self-organization way. Taking advantage of the nonequilibrium reaction in hydrogels, a simple mineralization strategy to closely mimic the formation of osteon in a mild physiological condition is developed. By constructing two reverse concentration gradients of ions from periphery to interior of cylindrical hydrogel, spatiotemporal self-organization of calcium phosphate in concentric rings is generated. It is noteworthy that minerals in different layers possess diverse contents and crystalline phases, which further guide the adhesion and spread of osteoblasts on these patterns, resembling the architecture and cytological behavior of osteon. Besides, theoretical data indicates the predominate role of ion concentrations and pH values of solution, in good accordance with experimental results. Independent of precise instruments, this lifelike method is easily obtained, cost-efficient, and effectively imitates the mineral deposition in osteon from a physiochemical view. The strategy may be expanded to develop other functional material patterns via spatiotemporal self-organization.
Topics: Bone and Bones; Haversian System; Hydrogels; Minerals; Osteoblasts
PubMed: 34921591
DOI: 10.1002/smll.202106649 -
Frontiers in Bioscience (Landmark... Jan 2012The research techniques available for investigation of secondary osteons in human bone enable establishment of their biological composition and quantification of their... (Review)
Review
The research techniques available for investigation of secondary osteons in human bone enable establishment of their biological composition and quantification of their mechanical properties. Further, the data generated through current research techniques facilitate studies on the significance of osteons in normal and pathological conditions, including via multi-scale modeling conducted with a view of building realistic models of virtual bone, suitable for applications from orthopaedic challenges to endocrine disorders. The understanding of the biomechanical function of the osteon requires clarification of the molecular-cellular processes that form, maintain and remodel the osteon and affect the mechanical function. In turn, the mechanical function affects the biology of the osteon. In retrospective, the investigation of osteons has focused on the unraveling of the complex combination of elementary components to discern the major factors that define the mechanical behavior. The micro-structural environment that leads to macroscopic fracture remains unclear. Arrangement, distribution and quality of the elementary components may participate in fracture risk. The latest results underline the fundamental role of the orientation of collagen type I and of carbonated hydroxyapatite crystallites.
Topics: Biomechanical Phenomena; Haversian System; Humans; Microscopy
PubMed: 22201820
DOI: 10.2741/4003 -
Biofabrication Apr 2022The integration of three-dimensional (3D) bioprinted scaffold's structure and function for critical-size bone defect repair is of immense significance. Inspired by the...
The integration of three-dimensional (3D) bioprinted scaffold's structure and function for critical-size bone defect repair is of immense significance. Inspired by the basic component of innate cortical bone tissue-osteons, many studies focus on biomimetic strategy. However, the complexity of hierarchical microchannels in the osteon, the requirement of mechanical strength of bone, and the biological function of angiogenesis and osteogenesis remain challenges in the fabrication of osteon-mimetic scaffolds. Therefore, we successfully built mimetic scaffolds with vertically central medullary canals, peripheral Haversian canals, and transverse Volkmann canals structures simultaneously by 3D bioprinting technology using polycaprolactone and bioink loading with bone marrow mesenchymal stem cells and bone morphogenetic protein-4. Subsequently, endothelial progenitor cells were seeded into the canals to enhance angiogenesis. The porosity and compressive properties of bioprinted scaffolds could be well controlled by altering the structure and canal numbers of the scaffolds. The osteon-mimetic scaffolds showed satisfactory biocompatibility and promotion of angiogenesis and osteogenesisand prompted the new blood vessels and new bone formation. In summary, this study proposes a biomimetic strategy for fabricating structured and functionalized 3D bioprinted scaffolds for vascularized bone tissue regeneration.
Topics: Biomimetics; Bioprinting; Bone Regeneration; Haversian System; Osteogenesis; Printing, Three-Dimensional; Tissue Engineering; Tissue Scaffolds
PubMed: 35417902
DOI: 10.1088/1758-5090/ac6700 -
Journal of Forensic Sciences Jan 2022Histological analysis of bone tissue has been used to explore a variety of questions relating to age-at-death, habitual behaviors, health, and nutritional stress....
Histological analysis of bone tissue has been used to explore a variety of questions relating to age-at-death, habitual behaviors, health, and nutritional stress. Identification of intact and fragmentary osteons is of key interest to many researchers in these studies, yet the definitions of these features vary between researchers making cross-study comparisons problematic. Furthermore, histological variable definitions are often ambiguous or require subjective classifications by the observer. As a result, and as indicated by previous studies, observer error and misclassification of certain variables, namely intact and fragmentary osteons, can be significant. This study proposes new definitions for intact and fragmentary osteons that are designed to limit observer subjectivity and also explore efficacy of combining osteon types into one variable. A sample of 30 6th rib cross-sections from a modern forensic population was used to test the validity of the proposed definitions. Observations of intact osteon population density (OPD(I)) and fragmentary osteon population density (OPD(F)) were made by three observers for each cross-section. These observations were used to explore the interobserver error associated with the proposed definitions and determine if combining variables into one variable (OPD) mitigates persisting classification difficulties. Results indicate that the proposed definitions significantly reduce interobserver error and misclassification of intact and fragmentary osteons. However, the interobserver error associated with fragmentary osteons is still high. Evaluation of the variables independently indicates that combining variables has potential to reduce the predictive strength of an age estimation model and the ability to interpret age-related bone remodeling.
Topics: Bone Remodeling; Bone and Bones; Femur; Forensic Medicine; Haversian System
PubMed: 34821385
DOI: 10.1111/1556-4029.14949 -
Biomaterials Advances Feb 2023Despite advances in bone tissue engineering, fabricating a scaffold which can be used as an implant for large bone defects remains challenge. One of the great importance...
Despite advances in bone tissue engineering, fabricating a scaffold which can be used as an implant for large bone defects remains challenge. One of the great importance in fabricating a biomimetic bone implant is considering the possibility of the integration of the structure and function of implants with hierarchical structure of bone. Herein, we propose a method to mimic the structural unit of compact bone, osteon, with spatial pattern of human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs) in the adjacent layers that mimic Haversian canal and lamella, respectively. To this end, coaxial extrusion-based bioprinting technique via a customized quadruple-layer core-shell nozzle was employed. 3D implant scaffold-cell construct was fabricated by using polyethylene glycol as a hollowing agent in the first layer, gelatin methacryloyl (GelMA) and alginate blended hydrogel encapsulating HUVEC cells with vascular endothelial growth factor nanoparticles in the second layer (vasculogenic layer) to mimic vascular vessel, and GelMA and alginate blended hydrogel containing hMSCs cells in the outer osteogenic layer to imitate lamella. Two types of bone minerals, whitlockite and hydroxyapatite, were incorporated in osteogenic layer to induce osteoblastic differentiation and enhance mechanical properties (the young's modules of nanocomposite increased from 35 kPa to 80 kPa). In-vitro evaluations demonstrated high cell viability (94 % within 10 days) and proliferation. Furthermore, ALP enzyme activity increased considerably within 2 weeks and mineralized extra cellular matrix considerably produced within 3 weeks. Also, a significant increase in osteogenic markers was observed indicating the presence of differentiated osteoblast cells. Therefore, the work indicates the potential of single step 3D bioprinting process to fabricate biomimetic osteons to use as bone grafts for regeneration.
Topics: Humans; Alginates; Bioprinting; Haversian System; Human Umbilical Vein Endothelial Cells; Hydrogels; Nanogels; Tissue Scaffolds; Vascular Endothelial Growth Factor A; Printing, Three-Dimensional
PubMed: 36584583
DOI: 10.1016/j.bioadv.2022.213254 -
Anatomical Science International Sep 2017Osteon structure has been widely studied in mammals, but osteon structure in dogs has received relatively little attention, especially in terms of whether aging has any...
Osteon structure has been widely studied in mammals, but osteon structure in dogs has received relatively little attention, especially in terms of whether aging has any effect on osteon structure. The aim of this study was to compare the osteon structure of both flat (scapula and os coxae) and long bones (humerus, radius, ulna, metacarpus, femur and tibia) of male puppy and adult Golden Retrievers. We examined five parameters: Haversian canal diameter, Haversian canal area, osteon diameter, osteon area, and number of lacunae per osteon. Our results show that the values for Haversian canal diameter were significantly higher in the os coxae and tibia, but significantly lower in the femur of adult dogs as compared to those of puppies. The Haversian canal diameter of the other bones investigated did not show any significant differences between puppies and adult dogs. The Haversian canal area was significantly greater in the os coxae, radius and femur of adult dogs than in those of puppies. The osteon diameter and area of every bone examined were significantly smaller in puppies than in adult dogs. Lastly, the number of lacunae per osteon showed the same trend as osteon diameter and area. Plexiform bone could be found in three bones in puppies, i.e. the femur, humerus and tibia. Overall, the results of this study should provide basic knowledge on the microanatomy of cortical bone in dogs and on the possible influence age.
Topics: Aging; Animals; Dogs; Haversian System; Humerus; Male; Pelvic Bones; Radius; Tibia
PubMed: 27084365
DOI: 10.1007/s12565-016-0345-y