Fracture Non-Union: A Review of Clinical Challenges and Future Research Needs

Sk, Stewart

doi:10.5704/moj.1907.001

Cited by 93 publications

(33 citation statements)

References 75 publications

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“…These critical-size defects can be caused by a variety of scenarios including trauma, tumor resection, or bacterial infections ( De Witte et al, 2018 ; Hasan et al, 2018 ). Moreover, external intervention is also required in the presence of fractures that have failed to heal completely (i.e., non-unions) ( Stewart, 2019 ). In clinical practice, autologous osseous material is still considered the gold standard, thanks to its inherent osteogenic, osteoconductive, and osteoinductive properties.…”

Section: Introductionmentioning

confidence: 99%

Antibacterial Composite Materials Based on the Combination of Polyhydroxyalkanoates With Selenium and Strontium Co-substituted Hydroxyapatite for Bone Regeneration

Marcello

Maqbool

Nigmatullin

et al. 2021

Front. Bioeng. Biotechnol.

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Due to the threat posed by the rapid growth in the resistance of microbial species to antibiotics, there is an urgent need to develop novel materials for biomedical applications capable of providing antibacterial properties without the use of such drugs. Bone healing represents one of the applications with the highest risk of postoperative infections, with potential serious complications in case of bacterial contaminations. Therefore, tissue engineering approaches aiming at the regeneration of bone tissue should be based on the use of materials possessing antibacterial properties alongside with biological and functional characteristics. In this study, we investigated the combination of polyhydroxyalkanoates (PHAs) with a novel antimicrobial hydroxyapatite (HA) containing selenium and strontium. Strontium was chosen for its well-known osteoinductive properties, while selenium is an emerging element investigated for its multi-functional activity as an antimicrobial and anticancer agent. Successful incorporation of such ions in the HA structure was obtained. Antibacterial activity against Staphylococcus aureus 6538P and Escherichia coli 8739 was confirmed for co-substituted HA in the powder form. Polymer-matrix composites based on two types of PHAs, P(3HB) and P(3HO-co-3HD-co-3HDD), were prepared by the incorporation of the developed antibacterial HA. An in-depth characterization of the composite materials was conducted to evaluate the effect of the filler on the physicochemical, thermal, and mechanical properties of the films. In vitro antibacterial testing showed that the composite samples induce a high reduction of the number of S. aureus 6538P and E. coli 8739 bacterial cells cultured on the surface of the materials. The films are also capable of releasing active ions which inhibited the growth of both Gram-positive and Gram-negative bacteria.

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Section: Introductionmentioning

confidence: 99%

Antibacterial Composite Materials Based on the Combination of Polyhydroxyalkanoates With Selenium and Strontium Co-substituted Hydroxyapatite for Bone Regeneration

Marcello

Maqbool

Nigmatullin

et al. 2021

Front. Bioeng. Biotechnol.

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“…However, up to 10% of bone fractures result in delayed healing or non-union (Zura et al, 2016). This risk rate is influenced by anatomical location, fracture severity and host factors such as age, smoking or the presence of comorbidities (Zura et al, 2016;Mills et al, 2017;Stewart, 2019). Current treatment options to prevent or cure these incidences present many drawbacks.…”

Section: Introductionmentioning

confidence: 99%

Towards in silico Models of the Inflammatory Response in Bone Fracture Healing

Lafuente-Gracia

Borgiani

Nasello

et al. 2021

Front. Bioeng. Biotechnol.

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In silico modeling is a powerful strategy to investigate the biological events occurring at tissue, cellular and subcellular level during bone fracture healing. However, most current models do not consider the impact of the inflammatory response on the later stages of bone repair. Indeed, as initiator of the healing process, this early phase can alter the regenerative outcome: if the inflammatory response is too strongly down- or upregulated, the fracture can result in a non-union. This review covers the fundamental information on fracture healing, in silico modeling and experimental validation. It starts with a description of the biology of fracture healing, paying particular attention to the inflammatory phase and its cellular and subcellular components. We then discuss the current state-of-the-art regarding in silico models of the immune response in different tissues as well as the bone regeneration process at the later stages of fracture healing. Combining the aforementioned biological and computational state-of-the-art, continuous, discrete and hybrid modeling technologies are discussed in light of their suitability to capture adequately the multiscale course of the inflammatory phase and its overall role in the healing outcome. Both in the establishment of models as in their validation step, experimental data is required. Hence, this review provides an overview of the different in vitro and in vivo set-ups that can be used to quantify cell- and tissue-scale properties and provide necessary input for model credibility assessment. In conclusion, this review aims to provide hands-on guidance for scientists interested in building in silico models as an additional tool to investigate the critical role of the inflammatory phase in bone regeneration.

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“…Nonunion occurs in approximately 5% of all fractures [ 1 – 3 ]. The basis of treatment of nonunion is to fully understand and address the causes.…”

Section: Introductionmentioning

confidence: 99%

Quantitative bone single-photon emission computed tomography imaging for uninfected nonunion: comparison of hypertrophic nonunion and non-hypertrophic nonunion

Zeng

Fukui

et al. 2021

J Orthop Surg Res

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Background Recently, a standardized uptake value (SUV) has been used to evaluate bone single-photon emission computed tomography (SPECT). The aim of this study was to investigate quantitative SPECT imaging of uninfected nonunion to compare hypertrophic nonunion and non-hypertrophic nonunion using volume-based parameters. Methods We evaluated 23 patients with uninfected nonunion who underwent SPECT acquisition 3 h after an injection of 99mTc-hydroxymethylene diphosphonate or 99mTc-methylene diphosphonate from April 2014 to November 2019. We reconstructed the acquired data and performed voxel-based quantitative analysis using the GI-BONE software. Quantitative parameters, maximum SUV (SUVmax), peak SUV (SUVpeak), and mean SUV (SUVmean) in the high and low uptake areas of nonunion were compared between hypertrophic nonunion and non-hypertrophic nonunion. The contralateral limb was used as a control, and the ratios of the quantitative parameters were calculated. Results The values for the quantitative parameters (high uptake area/low uptake area, respectively), SUVmax control ratio (12.13 ± 4.95/6.44 ± 4.71), SUVpeak control ratio (11.65 ± 4.58/6.45 ± 4.64), and SUVmean control ratio (11.94 ± 5.03/6.28 ± 4.95) for hypertrophic nonunion were higher than those for non-hypertrophic nonunion (7.82 ± 4.76/3.41 ± 2.09 (p = 0.065/0.12), 7.56 ± 4.51/3.61 ± 2.23 (p = 0.065/0.22), and 7.59 ± 5.18/3.05 ± 1.91 (p = 0.076/0.23)). Conclusions SUVmax, SUVpeak, and SUVmean control ratios obtained from bone SPECT images can quantitatively evaluate the biological activity of nonunions and may be an effective evaluation method for treatment decisions, especially the necessity of autologous bone grafting.

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Fracture Non-Union: A Review of Clinical Challenges and Future Research Needs

Cited by 93 publications

References 75 publications

Antibacterial Composite Materials Based on the Combination of Polyhydroxyalkanoates With Selenium and Strontium Co-substituted Hydroxyapatite for Bone Regeneration

Antibacterial Composite Materials Based on the Combination of Polyhydroxyalkanoates With Selenium and Strontium Co-substituted Hydroxyapatite for Bone Regeneration

Towards in silico Models of the Inflammatory Response in Bone Fracture Healing

Quantitative bone single-photon emission computed tomography imaging for uninfected nonunion: comparison of hypertrophic nonunion and non-hypertrophic nonunion

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