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  1. Article ; Online: Unraveling the influence of channel size and shape in 3D printed ceramic scaffolds on osteogenesis.

    Entezari, Ali / Wu, Qianju / Mirkhalaf, Mohammad / Lu, Zufu / Roohani, Iman / Li, Qing / Dunstan, Colin R / Jiang, Xinquan / Zreiqat, Hala

    Acta biomaterialia

    2024  

    Abstract: Bone has the capacity to regenerate itself for relatively small defects; however, this regenerative capacity is diminished in critical-size bone defects. The development of synthetic materials has risen as a distinct strategy to address this challenge. ... ...

    Abstract Bone has the capacity to regenerate itself for relatively small defects; however, this regenerative capacity is diminished in critical-size bone defects. The development of synthetic materials has risen as a distinct strategy to address this challenge. Effective synthetic materials to have emerged in recent years are bioceramic implants, which are biocompatible and highly bioactive. Yet nothing suitable for the repair of large bone defects has made the transition from laboratory to clinic. The clinical success of bioceramics has been shown to depend not only on the scaffold's intrinsic material properties but also on its internal porous geometry. This study aimed to systematically explore the implications of varying channel size, shape, and curvature in tissue scaffolds on in vivo bone regeneration outcomes. 3D printed bioceramic scaffolds with varying channel sizes (0.3 mm to 1.5 mm), shapes (circular vs rectangular), and curvatures (concave vs convex) were implanted in rabbit femoral defects for 8 weeks, followed by histological evaluation. We demonstrated that circular channel sizes of around 0.9 mm diameter significantly enhanced bone formation, compared to channel with diameters of 0.3 mm and 1.5 mm. Interestingly, varying channel shapes (rectangular vs circular) had no significant effect on the volume of newly formed bone. Furthermore, the present study systematically demonstrated the beneficial effect of concave surfaces on bone tissue growth in vivo, reinforcing previous in silico and in vitro findings. This study demonstrates that optimizing architectural configurations within ceramic scaffolds is crucial in enhancing bone regeneration outcomes. STATEMENT OF SIGNIFICANCE: Despite the explosion of work on developing synthetic scaffolds to repair bone defects, the amount of new bone formed by scaffolds in vivo remains suboptimal. Recent studies have illuminated the pivotal role of scaffolds' internal architecture in osteogenesis. However, these investigations have mostly remained confined to in silico and in vitro experiments. Among the in vivo studies conducted, there has been a lack of systematic analysis of individual architectural features. Herein, we utilized bioceramic 3D printing to conduct a systematic exploration of the effects of channel size, shape, and curvature on bone formation in vivo. Our results demonstrate the significant influence of channel size and curvature on in vivo outcomes. These findings provide invaluable insights into the design of more effective bone scaffolds.
    Language English
    Publishing date 2024-04-18
    Publishing country England
    Document type Journal Article
    ZDB-ID 2173841-5
    ISSN 1878-7568 ; 1742-7061
    ISSN (online) 1878-7568
    ISSN 1742-7061
    DOI 10.1016/j.actbio.2024.04.020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Personalized Baghdadite scaffolds: stereolithography, mechanics and in vivo testing.

    Mirkhalaf, Mohammad / Dao, Aiken / Schindeler, Aaron / Little, David G / Dunstan, Colin R / Zreiqat, Hala

    Acta biomaterialia

    2021  Volume 132, Page(s) 217–226

    Abstract: An ongoing challenge in the field of orthopedics is to produce a clinically relevant synthetic ceramic scaffold for the treatment of 'critical-sized' bone defects, which cannot heal without intervention. We had developed a bioactive ceramic (baghdadite, ... ...

    Abstract An ongoing challenge in the field of orthopedics is to produce a clinically relevant synthetic ceramic scaffold for the treatment of 'critical-sized' bone defects, which cannot heal without intervention. We had developed a bioactive ceramic (baghdadite, Ca₃ZrSi₂O₉) and demonstrated its outstanding bioactivity using traditional manufacturing techniques. Here, we report on the development of a versatile stereolithography printing technology that enabled fabrication of anatomically-shaped and -sized Baghdadite scaffolds. We assessed the in vivo bioactivity of these scaffolds in co-delivering of bone morphogenetic protein-2 (BMP2) and zoledronic acid (ZA) through bioresorbable coatings to induce bone formation and increase retention in a rat model of heterotopic ossification. Micro-computed tomography, histology, mechanical tests pre- and post-implantation, and mechanical modelling were used to assess bone ingrowth and its effects on the mechanics of the scaffolds. Bone ingrowth and the consequent mechanical properties of the scaffolds improved with increasing BMP2 dose. Co-delivery of ZA with BMP2 further improved this outcome. The significant bone formation within the scaffolds functionalized with 10 µg BMP2 and 2 µg ZA made them 2.3 × stiffer and 2.7 × stronger post-implantation and turned these inherently brittle scaffolds into a tough and deformable material. The effects of bone ingrowth on the mechanical properties of scaffolds were captured in a mechanical model that can be used in future clinical studies for non-destructive evaluation of scaffold's stiffness and strength as new bone forms. These results support the practical utilization of our versatile stereolithographic printing methods and BMP2/ZA functionalization to create fit-for-purpose personalized implants for clinical trials. STATEMENT OF SIGNIFICANCE: In this study, we addressed a long-standing challenge of developing a ceramic printing technology that enables fabrication of customizable anatomically-shaped and -sized bioceramic scaffolds with precise internal architectures using an inexpensive desktop printer. We also addressed another challenge related to delivery of pharmaceuticals. BMP2, currently available as a bone-inducing bioactive protein, is clinically administered in a collagen scaffold that has limited moldability and poor mechanical properties. The comparably stiffer and stronger 3D printed personalized Baghdadite scaffolds developed here can be readily functionalized with bioresorbable coatings containing BMP2 ± ZA. These innovations considerably improve on the prior art and are scalable for use in human surgery.
    Language English
    Publishing date 2021-03-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2173841-5
    ISSN 1878-7568 ; 1742-7061
    ISSN (online) 1878-7568
    ISSN 1742-7061
    DOI 10.1016/j.actbio.2021.03.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Inclusion of the in-chain sulfur in 3-thiaCTU increases the efficiency of mitochondrial targeting and cell killing by anticancer aryl-urea fatty acids.

    Rahman, Md Khalilur / Umashankar, Balasubrahmanyam / Choucair, Hassan / Pazderka, Curtis / Bourget, Kirsi / Chen, Yongjuan / Dunstan, Colin R / Rawling, Tristan / Murray, Michael

    European journal of pharmacology

    2022  Volume 939, Page(s) 175470

    Abstract: Mitochondria in tumor cells are functionally different from those in normal cells and could be targeted to develop new anticancer agents. We showed recently that the aryl-ureido fatty acid CTU is the prototype of a new class of mitochondrion-targeted ... ...

    Abstract Mitochondria in tumor cells are functionally different from those in normal cells and could be targeted to develop new anticancer agents. We showed recently that the aryl-ureido fatty acid CTU is the prototype of a new class of mitochondrion-targeted agents that kill cancer cells by increasing the production of reactive oxygen species (ROS), activating endoplasmic reticulum (ER)-stress and promoting apoptosis. However, prolonged treatment with high doses of CTU were required for in vivo anti-tumor activity. Thus, new strategies are now required to produce agents that have enhanced anticancer activity over CTU. In the present study we prepared a novel aryl-urea termed 3-thiaCTU, that contained an in-chain sulfur heteroatom, for evaluation in tumor cell lines and in mice carrying tumor xenografts. The principal finding to emerge was that 3-thiaCTU was several-fold more active than CTU in the activation of aryl-urea mechanisms that promoted cancer cell killing. Thus, in in vitro studies 3-thiaCTU disrupted the mitochondrial membrane potential, increased ROS production, activated ER-stress and promoted tumor cell apoptosis more effectively than CTU. 3-ThiaCTU was also significantly more active than CTUin vivo in mice that carried MDA-MB-231 cell xenografts. Compared to CTU, 3-thiaCTU prevented tumor growth more effectively and at much lower doses. These findings indicate that, in comparison to CTU, 3-thiaCTU is an aryl-urea with markedly enhanced activity that could now be suitable for development as a novel anticancer agent.
    Language English
    Publishing date 2022-12-18
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 80121-5
    ISSN 1879-0712 ; 0014-2999
    ISSN (online) 1879-0712
    ISSN 0014-2999
    DOI 10.1016/j.ejphar.2022.175470
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Discovering an unknown territory using atom probe tomography: Elemental exchange at the bioceramic scaffold/bone tissue interface.

    Holmes, Natalie P / Roohani, Iman / Entezari, Ali / Guagliardo, Paul / Mirkhalaf, Mohammad / Lu, Zufu / Chen, Yi-Sheng / Yang, Limei / Dunstan, Colin R / Zreiqat, Hala / Cairney, Julie M

    Acta biomaterialia

    2023  Volume 162, Page(s) 199–210

    Abstract: Here we report the first atom probe study to reveal the atomic-scale composition of in vivo bone formed in a bioceramic scaffold (strontium-hardystonite-gahnite) after 12-month implantation in a large bone defect in sheep tibia. The composition of the ... ...

    Abstract Here we report the first atom probe study to reveal the atomic-scale composition of in vivo bone formed in a bioceramic scaffold (strontium-hardystonite-gahnite) after 12-month implantation in a large bone defect in sheep tibia. The composition of the newly formed bone tissue differs to that of mature cortical bone tissue, and elements from the degrading bioceramic implant, particularly aluminium (Al), are present in both the newly formed bone and in the original mature cortical bone tissue at the perimeter of the bioceramic implant. Atom probe tomography confirmed that the trace elements are released from the bioceramic and are actively transported into the newly formed bone. NanoSIMS mapping, as a complementary technique, confirmed the distribution of the released ions from the bioceramic into the newly formed bone tissue within the scaffold. This study demonstrated the combined benefits of atom probe and nanoSIMS in assessing nanoscopic chemical composition changes at precise locations within the tissue/biomaterial interface. Such information can assist in understanding the interaction of scaffolds with surrounding tissue, hence permitting further iterative improvements to the design and performance of biomedical implants, and ultimately reducing the risk of complications or failure while increasing the rate of tissue formation. STATEMENT OF SIGNIFICANCE: The repair of critical-sized load-bearing bone defects is a challenge, and precisely engineered bioceramic scaffold implants is an emerging potential treatment strategy. However, we still do not understand the effect of the bioceramic scaffold implants on the composition of newly formed bone in vivo and surrounding existing mature bone. This article reports an innovative route to solve this problem, the combined power of atom probe tomography and nanoSIMS is used to spatially define elemental distributions across bioceramic implant sites. We determine the nanoscopic chemical composition changes at the Sr-HT Gahnite bioceramic/bone tissue interface, and importantly, provide the first report of in vivo bone tissue chemical composition formed in a bioceramic scaffold.
    MeSH term(s) Animals ; Sheep ; Tissue Scaffolds/chemistry ; Biocompatible Materials/chemistry ; Osteogenesis ; Bone and Bones/diagnostic imaging ; Tomography
    Chemical Substances Biocompatible Materials
    Language English
    Publishing date 2023-03-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2173841-5
    ISSN 1878-7568 ; 1742-7061
    ISSN (online) 1878-7568
    ISSN 1742-7061
    DOI 10.1016/j.actbio.2023.02.039
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Nicotinamide Mononucleotide Alleviates Osteoblast Senescence Induction and Promotes Bone Healing in Osteoporotic Mice.

    Lu, ZuFu / Jiang, Liting / Lesani, Pooria / Zhang, WenJie / Li, Ning / Luo, Danyang / Li, Yusi / Ye, Yulin / Bian, Ji / Wang, Guocheng / Dunstan, Colin R / Jiang, XinQuan / Zreiqat, Hala

    The journals of gerontology. Series A, Biological sciences and medical sciences

    2022  Volume 78, Issue 2, Page(s) 186–194

    Abstract: Combating the accumulated senescent cells and the healing of osteoporotic bone fractures in the older remains a significant challenge. Nicotinamide mononucleotide (NMN), a precursor of NAD+, is an excellent candidate for mitigating aging-related ... ...

    Abstract Combating the accumulated senescent cells and the healing of osteoporotic bone fractures in the older remains a significant challenge. Nicotinamide mononucleotide (NMN), a precursor of NAD+, is an excellent candidate for mitigating aging-related disorders. However, it is unknown if NMN can alleviate senescent cell induction and enhance osteoporotic bone fracture healing. Here we show that NMN treatment partially reverses the effects of tumor necrosis factor-alpha (TNF-α) on human primary osteoblasts (HOBs): senescent cell induction, diminished osteogenic differentiation ability, and intracellular NAD+ and NADH levels. Mechanistically, NMN restores the mitochondrial dysfunction in HOBs induced by TNF-α evidenced by increased mitochondrial membrane potential and reduced reactive oxidative species and mitochondrial mass. NMN also increases mitophagy activity by down-regulating P62 expression and up-regulating light chain 3B-II protein expression. In addition, the cell senescence protective effects of NMN on HOBs are mitigated by a mitophagy inhibitor (Bafilomycin A1). In vivo, NMN supplementation attenuates senescent cell induction in growth plates, partially prevents osteoporosis in an ovariectomized mouse model, and accelerates bone healing in osteoporotic mice. We conclude that NMN can be a novel and promising therapeutic candidate to enhance bone fracture healing capacity in the older.
    MeSH term(s) Mice ; Humans ; Animals ; Nicotinamide Mononucleotide/pharmacology ; NAD/metabolism ; Osteogenesis ; Tumor Necrosis Factor-alpha ; Osteoblasts/metabolism ; Osteoporosis
    Chemical Substances Nicotinamide Mononucleotide (1094-61-7) ; NAD (0U46U6E8UK) ; Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2022-09-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1223643-3
    ISSN 1758-535X ; 1079-5006
    ISSN (online) 1758-535X
    ISSN 1079-5006
    DOI 10.1093/gerona/glac175
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Book: A tissue regeneration approach to bone and cartilage repair

    Zreiqat, Hala / Dunstan, Colin R / Rosen, Vicki

    (Mechanical engineering series,)

    2015  

    Author's details Hala Zreiqat, Colin R. Dunstan, Vicki Rosen, editors
    Series title Mechanical engineering series,
    MeSH term(s) Bone Regeneration ; Cartilage, Articular/growth & development ; Chondrogenesis ; Tissue Engineering/methods
    Language English
    Size vi, 254 pages :, illustrations ;, 25 cm.
    Document type Book
    ISBN 9783319132655 ; 3319132652 ; 9783319132662 ; 3319132660
    Database Catalogue of the US National Library of Medicine (NLM)

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  7. Article ; Online: Functional Ultra-High Molecular Weight Polyethylene Composites for Ligament Reconstructions and Their Targeted Applications in the Restoration of the Anterior Cruciate Ligament.

    Wahed, Sonia B / Dunstan, Colin R / Boughton, Philip A / Ruys, Andrew J / Faisal, Shaikh N / Wahed, Tania B / Salahuddin, Bidita / Cheng, Xinying / Zhou, Yang / Wang, Chun H / Islam, Mohammad S / Aziz, Shazed

    Polymers

    2022  Volume 14, Issue 11

    Abstract: The selection of biomaterials as biomedical implants is a significant challenge. Ultra-high molecular weight polyethylene (UHMWPE) and composites of such kind have been extensively used in medical implants, notably in the bearings of the hip, knee, and ... ...

    Abstract The selection of biomaterials as biomedical implants is a significant challenge. Ultra-high molecular weight polyethylene (UHMWPE) and composites of such kind have been extensively used in medical implants, notably in the bearings of the hip, knee, and other joint prostheses, owing to its biocompatibility and high wear resistance. For the Anterior Cruciate Ligament (ACL) graft, synthetic UHMWPE is an ideal candidate due to its biocompatibility and extremely high tensile strength. However, significant problems are observed in UHMWPE based implants, such as wear debris and oxidative degradation. To resolve the issue of wear and to enhance the life of UHMWPE as an implant, in recent years, this field has witnessed numerous innovative methodologies such as biofunctionalization or high temperature melting of UHMWPE to enhance its toughness and strength. The surface functionalization/modification/treatment of UHMWPE is very challenging as it requires optimizing many variables, such as surface tension and wettability, active functional groups on the surface, irradiation, and protein immobilization to successfully improve the mechanical properties of UHMWPE and reduce or eliminate the wear or osteolysis of the UHMWPE implant. Despite these difficulties, several surface roughening, functionalization, and irradiation processing technologies have been developed and applied in the recent past. The basic research and direct industrial applications of such material improvement technology are very significant, as evidenced by the significant number of published papers and patents. However, the available literature on research methodology and techniques related to material property enhancement and protection from wear of UHMWPE is disseminated, and there is a lack of a comprehensive source for the research community to access information on the subject matter. Here we provide an overview of recent developments and core challenges in the surface modification/functionalization/irradiation of UHMWPE and apply these findings to the case study of UHMWPE for ACL repair.
    Language English
    Publishing date 2022-05-28
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527146-5
    ISSN 2073-4360 ; 2073-4360
    ISSN (online) 2073-4360
    ISSN 2073-4360
    DOI 10.3390/polym14112189
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Reprogramming of human fibroblasts into osteoblasts by insulin-like growth factor-binding protein 7.

    Lu, ZuFu / Chiu, Joyce / Lee, Lucinda R / Schindeler, Aaron / Jackson, Miriam / Ramaswamy, Yogambha / Dunstan, Colin R / Hogg, Philip J / Zreiqat, Hala

    Stem cells translational medicine

    2020  Volume 9, Issue 3, Page(s) 403–415

    Abstract: The induced pluripotent stem cell (iPSC) is a promising cell source for tissue regeneration. However, the therapeutic value of iPSC technology is limited due to the complexity of induction protocols and potential risks of teratoma formation. A trans- ... ...

    Abstract The induced pluripotent stem cell (iPSC) is a promising cell source for tissue regeneration. However, the therapeutic value of iPSC technology is limited due to the complexity of induction protocols and potential risks of teratoma formation. A trans-differentiation approach employing natural factors may allow better control over reprogramming and improved safety. We report here a novel approach to drive trans-differentiation of human fibroblasts into functional osteoblasts using insulin-like growth factor binding protein 7 (IGFBP7). We initially determined that media conditioned by human osteoblasts can induce reprogramming of human fibroblasts to functional osteoblasts. Proteomic analysis identified IGFBP7 as being significantly elevated in media conditioned with osteoblasts compared with those with fibroblasts. Recombinant IGFBP7 induced a phenotypic switch from fibroblasts to osteoblasts. The switch was associated with senescence and dependent on autocrine IL-6 signaling. Our study supports a novel strategy for regenerating bone by using IGFBP7 to trans-differentiate fibroblasts to osteoblasts.
    MeSH term(s) Animals ; Fibroblasts/metabolism ; Humans ; Insulin-Like Growth Factor Binding Proteins/genetics ; Mice ; Mice, Nude ; Osteoblasts/metabolism ; Xenograft Model Antitumor Assays
    Chemical Substances Insulin-Like Growth Factor Binding Proteins
    Language English
    Publishing date 2020-01-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2642270-0
    ISSN 2157-6580 ; 2157-6580
    ISSN (online) 2157-6580
    ISSN 2157-6580
    DOI 10.1002/sctm.19-0281
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Design and evaluation of 3D-printed Sr-HT-Gahnite bioceramic for FDA regulatory submission: A Good Laboratory Practice sheep study.

    Newsom, Ellen T / Sadeghpour, Ameneh / Entezari, Ali / Vinzons, Joan Lace U / Stanford, Ralph E / Mirkhalaf, Mohammad / Chon, Daniel / Dunstan, Colin R / Zreiqat, Hala

    Acta biomaterialia

    2022  Volume 156, Page(s) 214–221

    Abstract: There is an unmet clinical need for a spinal fusion implant material that recapitulates the biological and mechanical performance of natural bone. We have developed a bioceramic, Sr-HT-Gahnite, which has been identified as a potential fusion device ... ...

    Abstract There is an unmet clinical need for a spinal fusion implant material that recapitulates the biological and mechanical performance of natural bone. We have developed a bioceramic, Sr-HT-Gahnite, which has been identified as a potential fusion device material. This material has the capacity to transform the future of the global interbody devices market, with follow on social, economic, and environmental benefits, rooted in its remarkable combination of mechanical properties and bioactivity. In this study, and in line with FDA requirements, the in vivo preclinical systemic biological safety of a Sr-HT-Gahnite interbody fusion device is assessed over 26 weeks in sheep under good laboratory practice (GLP). Following the in-life phase, animals are assessed for systemic biological effects via blood haematology and clinical biochemistry, strontium dosage analysis in the blood and wool, and histopathology examination of the distant organs including adrenals, brain, heart, kidneys, liver, lungs and bronchi, skeletal muscle, spinal nerves close to the implanted sites, ovaries, and draining lymph nodes. Our results show that no major changes in blood haematology or biochemistry parameters are observed, no systemic distribution of strontium to the blood and wool, and no macroscopic or histopathological abnormalities in the distant organs when Sr-HT-Gahnite was implanted, compared to baseline and control values. Together, these results indicate the systemic safety of the Sr-HT-Gahnite interbody fusion device. The results of this study extend to the systemic safety of other Sr-HT-Gahnite implanted medical devices in contact with bone or tissue, of similar size and manufactured using the described processes. STATEMENT OF SIGNIFICANCE: This paper is considered original and innovative as it is the first that thoroughly reports the systemic biological safety of previously undescribed bioceramic material, Sr-HT-Gahnite. The study has been performed under good laboratory practice, in line with FDA requirements for assessment of a new interbody fusion device, making the results broadly applicable to the translation of sheep models to the human cervical spine; and also the translation of Sr-HT-Gahnite as a biomaterial for use in additional applications. We expect this study to be of broad interest to the readership of Acta Biomaterilia. Its findings are directly applicable to researchers and clinicians working in bone repair and the development of synthetic biomaterials.
    MeSH term(s) Humans ; Animals ; Sheep ; Biocompatible Materials/chemistry ; Prostheses and Implants ; Bone and Bones ; Strontium/pharmacology ; Strontium/chemistry ; Printing, Three-Dimensional ; Spinal Fusion/methods
    Chemical Substances Biocompatible Materials ; Strontium (YZS2RPE8LE)
    Language English
    Publishing date 2022-01-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2173841-5
    ISSN 1878-7568 ; 1742-7061
    ISSN (online) 1878-7568
    ISSN 1742-7061
    DOI 10.1016/j.actbio.2022.01.035
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Role of mathematical modeling in bone fracture healing.

    Pivonka, Peter / Dunstan, Colin R

    BoneKEy reports

    2012  Volume 1, Page(s) 221

    Abstract: Bone fracture healing is a complex physiological process commonly described by a four-phase model consisting of an inflammatory phase, two repair phases with soft callus formation followed by hard callus formation, and a remodeling phase, or more ... ...

    Abstract Bone fracture healing is a complex physiological process commonly described by a four-phase model consisting of an inflammatory phase, two repair phases with soft callus formation followed by hard callus formation, and a remodeling phase, or more recently by an anabolic/catabolic model. Data from humans and animal models have demonstrated crucial environmental conditions for optimal fracture healing, including the mechanical environment, blood supply and availability of mesenchymal stem cells. Fracture healing spans multiple length and time scales, making it difficult to know precisely which factors and/or phases to manipulate in order to obtain optimal fracture-repair outcomes. Deformations resulting from physiological loading or fracture fixation at the organ scale are sensed at the cellular scale by cells inside the fracture callus. These deformations together with autocrine and paracrine signals determine cellular differentiation, proliferation and migration. The local repair activities lead to new bone formation and stabilization of the fracture. Although experimental data are available at different spatial and temporal scales, it is not clear how these data can be linked to provide a holistic view of fracture healing. Mathematical modeling is a powerful tool to quantify conceptual models and to establish the missing links between experimental data obtained at different scales. The objective of this review is to introduce mathematical modeling to readers who are not familiar with this methodology and to demonstrate that once validated, such models can be used for hypothesis testing and to assist in clinical treatment as will be shown for the example of atrophic nonunions.
    Language English
    Publishing date 2012-11-14
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2816308-4
    ISSN 2047-6396
    ISSN 2047-6396
    DOI 10.1038/bonekey.2012.221
    Database MEDical Literature Analysis and Retrieval System OnLINE

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