Bioengineering

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2 pages, 153 KiB

Open AccessEditorial

Advances in Fracture Healing Research

by Sabrina Ehnert and Tina Histing

Bioengineering 2024, 11(1), 67; https://doi.org/10.3390/bioengineering11010067 - 9 Jan 2024

Viewed by 1709

Abstract

Despite a constant refinement of surgical techniques and bone fixation methods, up to 15% of fractures result in impaired healing or even develop a non-union [...] Full article

(This article belongs to the Special Issue Advances in Fracture Healing Research)

Research

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18 pages, 9241 KiB

Open AccessArticle

Focused Low-Intensity Pulsed Ultrasound (FLIPUS) Mitigates Apoptosis of MLO-Y4 Osteocyte-like Cells

by Regina Puts, Aseel Khaffaf, Maria Shaka, Hui Zhang and Kay Raum

Bioengineering 2023, 10(3), 387; https://doi.org/10.3390/bioengineering10030387 - 21 Mar 2023

Cited by 3 | Viewed by 2410

Abstract

Long cytoplasmic processes of osteocytes orchestrate bone activity by integration of biochemical and mechanical signals and regulate load-induced bone adaptation. Low-Intensity Pulsed Ultrasound (LIPUS) is a clinically used technique for fracture healing that delivers mechanical impulses to the damaged bone tissue in a [...] Read more.

Long cytoplasmic processes of osteocytes orchestrate bone activity by integration of biochemical and mechanical signals and regulate load-induced bone adaptation. Low-Intensity Pulsed Ultrasound (LIPUS) is a clinically used technique for fracture healing that delivers mechanical impulses to the damaged bone tissue in a non-invasive and non-ionizing manner. The mechanism of action of LIPUS is still controversially discussed in the scientific community. In this study, the effect of focused LIPUS (FLIPUS) on the survival of starved MLO-Y4 osteocytes was investigated in vitro. Osteocytes stimulated for 10 min with FLIPUS exhibited extended dendrites, which formed frequent connections to neighboring cells and spanned longer distances. The sonicated cells displayed thick actin bundles and experienced increase in expression of connexin 43 (Cx43) proteins, especially on their dendrites, and E11 glycoprotein, which is responsible for the elongation of cellular cytoplasmic processes. After stimulation, expression of cell growth and survival genes as well as genes related to cell–cell communication was augmented. In addition, cell viability was improved after the sonication, and a decrease in ATP release in the medium was observed. In summary, FLIPUS mitigated apoptosis of starved osteocytes, which is likely related to the formation of the extensive dendritic network that ensured cell survival. Full article

(This article belongs to the Special Issue Advances in Fracture Healing Research)

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12 pages, 7892 KiB

Open AccessArticle

Development of a Metaphyseal Non-Union Model in the Osteoporotic Rat Femur

by Amelie Deluca, Andrea Wagner, Bettina Faustini, Nadja Weissenbacher, Christian Deininger, Florian Wichlas, Herbert Tempfer, Ernst J. Mueller and Andreas Traweger

Bioengineering 2023, 10(3), 338; https://doi.org/10.3390/bioengineering10030338 - 7 Mar 2023

Cited by 2 | Viewed by 1976

Abstract

The aim of this current study was to establish a metaphyseal femoral non-union model in osteoporotic rats by comparing a power tool versus a manual tool for fracture creation. Twelve adult female Sprague Dawley rats were ovariectomized (OVX) and received a special diet [...] Read more.

The aim of this current study was to establish a metaphyseal femoral non-union model in osteoporotic rats by comparing a power tool versus a manual tool for fracture creation. Twelve adult female Sprague Dawley rats were ovariectomized (OVX) and received a special diet for 6 weeks. Biweekly pQCT measurements confirmed a significant reduction in the cancellous and total bone mineral density in OVX rats compared to control (CTRL) animals. After 6 weeks, OVX rats underwent surgery creating a distal metaphyseal osteotomy, either using a piezoelectric- (n = 6) or a manual Gigli wire (n = 6) saw. Fractures were stabilized with a Y-shaped mini-locking plate. Within each group, three rats received Alginate directly into the fracture gap. OVX animals gained more weight over 8 weeks compared to CTRL animals. pQCT analysis showed a significant difference in the volumetric cancellous bone mineral density between OVX and CTRL rats. A histological examination of the osteoporotic phenotype was completed. Radiographic evaluation and Masson–Goldner trichrome staining with the piezoelectric saw failed to demonstrate bony bridging or a callus formation. New bone formation and complete healing were seen after 6 weeks in the Gigli group. For the creation of a metaphyseal atrophic non-union in the osteoporotic bone, a piezoelectric saw should be used. Full article

(This article belongs to the Special Issue Advances in Fracture Healing Research)

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15 pages, 3197 KiB

Open AccessArticle

Radiographic, Biomechanical and Histological Characterization of Femoral Fracture Healing in Aged CD-1 Mice

by Maximilian M. Menger, Ruben Manuschewski, Sabrina Ehnert, Mika F. Rollmann, Tanja C. Maisenbacher, Anne L. Tobias, Michael D. Menger, Matthias W. Laschke and Tina Histing

Bioengineering 2023, 10(2), 275; https://doi.org/10.3390/bioengineering10020275 - 20 Feb 2023

Cited by 6 | Viewed by 1992

Abstract

With a gradually increasing elderly population, the treatment of geriatric patients represents a major challenge for trauma and reconstructive surgery. Although, it is well established that aging affects bone metabolism, it is still controversial if aging impairs bone healing. Accordingly, we investigated fracture [...] Read more.

With a gradually increasing elderly population, the treatment of geriatric patients represents a major challenge for trauma and reconstructive surgery. Although, it is well established that aging affects bone metabolism, it is still controversial if aging impairs bone healing. Accordingly, we investigated fracture healing in young adult (3–4 months) and aged (16–18 months) CD-1 mice using a stable closed femoral fracture model. Bone healing was analyzed by radiographic, biomechanical and histological analysis at 1, 2, 3, 4 and 5 weeks after fracture. Our results demonstrated an increased callus diameter to femoral diameter ratio in aged animals at later time points of fracture healing when compared to young adult mice. Moreover, our biomechanical analysis revealed a significantly decreased bending stiffness at 3 and 4 weeks after fracture in aged animals. In contrast, at 5 weeks after fracture, the analysis showed no significant difference in bending stiffness between the two study groups. Additional histological analysis showed a delayed endochondral ossification in aged animals as well as a higher amounts of fibrous tissue at early healing time points. These findings indicate a delayed process of callus remodeling in aged CD-1 mice, resulting in a delayed fracture healing when compared to young adult animals. However, the overall healing capacity of the fractured femora was not affected by aging. Full article

(This article belongs to the Special Issue Advances in Fracture Healing Research)

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22 pages, 4214 KiB

Open AccessArticle

A New Osteogenic Membrane to Enhance Bone Healing: At the Crossroads between the Periosteum, the Induced Membrane, and the Diamond Concept

by Julie Manon, Robin Evrard, Lies Fievé, Caroline Bouzin, Delphine Magnin, Daela Xhema, Tom Darius, Eliano Bonaccorsi-Riani, Pierre Gianello, Pierre-Louis Docquier, Thomas Schubert, Benoît Lengelé, Catherine Behets and Olivier Cornu

Bioengineering 2023, 10(2), 143; https://doi.org/10.3390/bioengineering10020143 - 21 Jan 2023

Cited by 10 | Viewed by 2684

Abstract

The lack of viability of massive bone allografts for critical-size bone defect treatment remains a challenge in orthopedic surgery. The literature has reviewed the advantages of a multi-combined treatment with the synergy of an osteoconductive extracellular matrix (ECM), osteogenic stem cells, and growth [...] Read more.

The lack of viability of massive bone allografts for critical-size bone defect treatment remains a challenge in orthopedic surgery. The literature has reviewed the advantages of a multi-combined treatment with the synergy of an osteoconductive extracellular matrix (ECM), osteogenic stem cells, and growth factors (GFs). Questions are still open about the need for ECM components, the influence of the decellularization process on the latter, the related potential loss of function, and the necessity of using pre-differentiated cells. In order to fill in this gap, a bone allograft surrounded by an osteogenic membrane made of a decellularized collagen matrix from human fascia lata and seeded with periosteal mesenchymal stem cells (PMSCs) was analyzed in terms of de-/recellularization, osteogenic properties, PMSC self-differentiation, and angiogenic potential. While the decellularization processes altered the ECM content differently, the main GF content was decreased in soft tissues but relatively increased in hard bone tissues. The spontaneous osteogenic differentiation was necessarily obtained through contact with a mineralized bone matrix. Trying to deepen the knowledge on the complex matrix–cell interplay could further propel these tissue engineering concepts and lead us to provide the biological elements that allow bone integration in vivo. Full article

(This article belongs to the Special Issue Advances in Fracture Healing Research)

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12 pages, 2568 KiB

Open AccessArticle

Bone Morphogenetic Protein 2 Promotes Bone Formation in Bone Defects in Which Bone Remodeling Is Suppressed by Long-Term and High-Dose Zoledronic Acid

by Young Jae Moon, Seongyup Jeong and Kwang-Bok Lee

Bioengineering 2023, 10(1), 86; https://doi.org/10.3390/bioengineering10010086 - 9 Jan 2023

Cited by 6 | Viewed by 1800

Abstract

The use of long-term and high-dose bisphosphate is associated with severely suppressed bone turnover and the delayed union of fractures. However, therapeutic methods to overcome the negative effects of bisphosphonate use are lacking. Bone morphogenetic proteins (BMPs) are powerful osteoinductive proteins. The development [...] Read more.

The use of long-term and high-dose bisphosphate is associated with severely suppressed bone turnover and the delayed union of fractures. However, therapeutic methods to overcome the negative effects of bisphosphonate use are lacking. Bone morphogenetic proteins (BMPs) are powerful osteoinductive proteins. The development of the delivery system using BMP has been verified to have an excellent effect on fracture healing and the enhancement of osteointegration. We hypothesized that BMPs had similar effects as autografts in patients with decreased bone healing potential due to long-term bisphosphonate treatment. Forty rats were divided into the following four groups depending upon the materials implanted into the femoral defect after ten weeks of bisphosphonate (zoledronic acid) injections: Group I: absorbable collagen sponge (control); group II: demineralized freeze-dried bone graft; group III: autogenous bone graft; and group IV: rhBMP-2 with an absorbable collagen sponge. Radiographic union, micro-computed tomography (CT) analysis, manual palpation, and histologic analysis were evaluated. The radiographic union rate, manual union rate, and micro-CT bone volume in groups III and IV were significantly higher than those in groups I and II. Groups III and IV showed similar results to each other. Although the amount of immature bone in the BMP-treated group was large, the effect was similar to that of autografts in the bone defect model in which bone turnover was severely reduced by bisphosphonate treatment. BMP might be a good substitute for autografts in patients with decreased bone healing potential due to long-term bisphosphonate treatment. Full article

(This article belongs to the Special Issue Advances in Fracture Healing Research)

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11 pages, 1855 KiB

Open AccessArticle

Bond Strength and Adhesion Mechanisms of Novel Bone Adhesives

by Sarah J. Upson, Matthew J. Benning, David A. Fulton, Ian P. Corbett, Kenneth W. Dalgarno and Matthew J. German

Bioengineering 2023, 10(1), 78; https://doi.org/10.3390/bioengineering10010078 - 6 Jan 2023

Cited by 2 | Viewed by 2246

Abstract

Bone adhesives offer distinct advantages over the use of screws to attached internal fixation plates (IFPs). As the chemical composition of bone is similar to dentine, it is possible that the types of monomers used to make dentine adhesives could be utilised to [...] Read more.

Bone adhesives offer distinct advantages over the use of screws to attached internal fixation plates (IFPs). As the chemical composition of bone is similar to dentine, it is possible that the types of monomers used to make dentine adhesives could be utilised to affix IFPs to bone. The ability to attach a bio-resorbable IFP to porcine bone was assessed for the monomer 10-methacryloyloxydecyl dihydrogen phosphate (MDP), used either as a homopolymer or a copolymer with urethane dimethacrylate (MDP + U). Additionally, the addition of a priming step (MDP + U + P) was evaluated. The chemical interactions of the monomers with bone were assessed using XRD and imaged using TEM, revealing the formation of nano-layered structures with the MDP primer, something we believe has not been reported on bone. In a 6-week artificial aging study both MDP + U and MDP + U + P demonstrated adequate shear bond strength to affix bio-resorbable IFPs. The cytotoxicity profiles of the adhesive formulations were determined using indirect and direct contact with MC3T3 cells, with indirect conditions suggesting the MDP + U + P is as cytocompatible as the resorbable IFP. The findings of this study suggest our newly developed adhesive has the potential to be used as a bone adhesive to affix bioresorbable IFPs. Full article

(This article belongs to the Special Issue Advances in Fracture Healing Research)

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15 pages, 3205 KiB

Open AccessArticle

Electrical Stimulation Therapy and HA/TCP Composite Scaffolds Modulate the Wnt Pathways in Bone Regeneration of Critical-Sized Defects

by Júlia Venturini Helaehil, Luiza Venturini Helaehil, Laryssa Fernanda Alves, Boyang Huang, Milton Santamaria-Jr, Paulo Bartolo and Guilherme Ferreira Caetano

Bioengineering 2023, 10(1), 75; https://doi.org/10.3390/bioengineering10010075 - 6 Jan 2023

Cited by 6 | Viewed by 2317

Abstract

Critical bone defects are the most difficult challenges in the area of tissue repair. Polycaprolactone (PCL) scaffolds, associated with hydroxyapatite (HA) and tricalcium phosphate (TCP), are reported to have an enhanced bioactivity. Moreover, the use of electrical stimulation (ES) has overcome the lack [...] Read more.

Critical bone defects are the most difficult challenges in the area of tissue repair. Polycaprolactone (PCL) scaffolds, associated with hydroxyapatite (HA) and tricalcium phosphate (TCP), are reported to have an enhanced bioactivity. Moreover, the use of electrical stimulation (ES) has overcome the lack of bioelectricity at the bone defect site and compensated the endogenous electrical signals. Such treatments could modulate cells and tissue signaling pathways. However, there is no study investigating the effects of ES and bioceramic composite scaffolds on bone tissue formation, particularly in the view of cell signaling pathway. This study aims to investigate the application of HA/TCP composite scaffolds and ES and their effects on the Wingless-related integration site (Wnt) pathway in critical bone repair. Critical bone defects (25 mm²) were performed in rats, which were divided into four groups: PCL, PCL + ES, HA/TCP and HA/TCP + ES. The scaffolds were grafted at the defect site and applied with the ES application twice a week using 10 µA of current for 5 min. Bone samples were collected for histomorphometry, immunohistochemistry and molecular analysis. At the Wnt canonical pathway, HA/TCP and HA/TCP + ES groups showed higher Wnt1 and β-catenin gene expression levels, especially HA/TCP. Moreover, HA/TCP + ES presented higher Runx2, Osterix and Bmp-2 levels. At the Wnt non-canonical pathway, HA/TCP group showed higher voltage-gated calcium channel (Vgcc), calmodulin-dependent protein kinase II, and Wnt5a genes expression, while HA/TCP + ES presented higher protein expression of VGCC and calmodulin (CaM) at the same period. The decrease in sclerostin and osteopontin genes expressions and the lower bone sialoprotein II in the HA/TCP + ES group may be related to the early bone remodeling. This study shows that the use of ES modulated the Wnt pathways and accelerated the osteogenesis with improved tissue maturation. Full article

(This article belongs to the Special Issue Advances in Fracture Healing Research)

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12 pages, 1974 KiB

Open AccessArticle

Fracture Healing in Elderly Mice and the Effect of an Additional Severe Blood Loss: A Radiographic and Biomechanical Murine Study

by Katrin Bundkirchen, Weikang Ye, Aleksander J. Nowak, Stefan Lienenklaus, Bastian Welke, Borna Relja and Claudia Neunaber

Bioengineering 2023, 10(1), 70; https://doi.org/10.3390/bioengineering10010070 - 5 Jan 2023

Cited by 3 | Viewed by 1708

Abstract

Femoral fractures and severe bleeding frequently occur in old patients showing a delayed healing. As there are no studies investigating the combined effect of high age and severe blood loss on fracture healing, this was examined radiographically and biomechanically in this study. Therefore, [...] Read more.

Femoral fractures and severe bleeding frequently occur in old patients showing a delayed healing. As there are no studies investigating the combined effect of high age and severe blood loss on fracture healing, this was examined radiographically and biomechanically in this study. Therefore, young and old male mice were randomly assigned to three operation groups. In the fracture group (Fx), external fixator and osteotomy were applied to the femur. The combined trauma group (THFx) additionally received a pressure-controlled hemorrhage. Sham animals were only implanted with arterial catheter and external fixator. Sacrifice was performed after three weeks and bone healing was evaluated radiologically via µCT, as well as biomechanically using a three-point bending test. A decreased share of callus/total bone volume was observed in old mice with blood loss compared to old Fx. Hemorrhagic shock also reduced the trabecular number in old mice compared to Fx and young THFx. Moreover, a lower elastic limit in old Sham mice without fracture was revealed. Fracture combined with a high loss of blood further reduced the elastic limit in old mice compared to isolated Fx in old animals. In conclusion, this study showed that severe blood loss has a higher negative effect in old mice compared to young ones. Full article

(This article belongs to the Special Issue Advances in Fracture Healing Research)

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13 pages, 3945 KiB

Open AccessArticle

About 3D Printability of Thermoplastic Collagen for Biomedical Applications

by Marina Passos, Sergej Zankovic, Graça Minas, Enno Klüver, Marit Baltzer, Hagen Schmal and Michael Seidenstuecker

Bioengineering 2022, 9(12), 780; https://doi.org/10.3390/bioengineering9120780 - 7 Dec 2022

Cited by 1 | Viewed by 2175

Abstract

With more than 1.5 million total knee and hip implants placed each year, there is an urgent need for a drug delivery system that can effectively support the repair of bone infections. Scaffolds made of natural biopolymers are widely used for this purpose [...] Read more.

With more than 1.5 million total knee and hip implants placed each year, there is an urgent need for a drug delivery system that can effectively support the repair of bone infections. Scaffolds made of natural biopolymers are widely used for this purpose due to their biocompatibility, biodegradability, and suitable mechanical properties. However, the poor processability is a bottleneck, as highly customizable scaffolds are desired. The aim of the present research is to develop a scaffold made of thermoplastic collagen (TC) using 3D printing technology. The viscosity of the material was measured using a rheometer. A 3D bioplotter was used to fabricate the scaffolds out of TC. The mechanical properties of the TC scaffolds were performed using tension/compression testing on a Zwick/Roell universal testing machine. TC shows better compressibility with increasing temperature and a decrease in dynamic viscosity (η), storage modulus (G′), and loss modulus (G″). The compressive strength of the TC scaffolds was between 3–10 MPa, depending on the geometry (cylinder or cuboid, with different infills). We have demonstrated for the first time that TC can be used to fabricate porous scaffolds by 3D printing in various geometries. Full article

(This article belongs to the Special Issue Advances in Fracture Healing Research)

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24 pages, 3159 KiB

Open AccessArticle

Developing Porous Ortho- and Pyrophosphate-Containing Glass Microspheres; Structural and Cytocompatibility Characterisation

by Ben Milborne, Lauren Murrell, Ian Cardillo-Zallo, Jeremy Titman, Louise Briggs, Colin Scotchford, Alexander Thompson, Robert Layfield and Ifty Ahmed

Bioengineering 2022, 9(11), 611; https://doi.org/10.3390/bioengineering9110611 - 25 Oct 2022

Cited by 5 | Viewed by 2208

Abstract

Phosphate-based glasses (PBGs) are promising materials for bone repair and regeneration as they can be formulated to be compositionally similar to the inorganic components of bone. Alterations to the PBG formulation can be used to tailor their degradation rates and subsequent release of [...] Read more.

Phosphate-based glasses (PBGs) are promising materials for bone repair and regeneration as they can be formulated to be compositionally similar to the inorganic components of bone. Alterations to the PBG formulation can be used to tailor their degradation rates and subsequent release of biotherapeutic ions to induce cellular responses, such as osteogenesis. In this work, novel invert-PBGs in the series xP₂O₅·(56 − x)CaO·24MgO·20Na₂O (mol%), where x is 40, 35, 32.5 and 30 were formulated to contain pyro (Q¹) and orthophosphate (Q⁰) species. These PBGs were processed into highly porous microspheres (PMS) via flame spheroidisation, with ~68% to 75% porosity levels. Compositional and structural analysis using EDX and ³¹P-MAS NMR revealed that significant depolymerisation occurred with reducing phosphate content which increased further when PBGs were processed into PMS. A decrease from 50% to 0% in Q² species and an increase from 6% to 35% in Q⁰ species was observed for the PMS when the phosphate content decreased from 40 to 30 mol%. Ion release studies also revealed up to a four-fold decrease in cations and an eight-fold decrease in phosphate anions released with decreasing phosphate content. In vitro bioactivity studies revealed that the orthophosphate-rich PMS had favourable bioactivity responses after 28 days of immersion in simulated body fluid (SBF). Indirect and direct cell culture studies confirmed that the PMS were cytocompatible and supported cell growth and proliferation over 7 days of culture. The P30 PMS with ~65% pyro and ~35% ortho phosphate content revealed the most favourable properties and is suggested to be highly suitable for bone repair and regeneration, especially for orthobiologic applications owing to their highly porous morphology. Full article

(This article belongs to the Special Issue Advances in Fracture Healing Research)

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8 pages, 7136 KiB

Open AccessCommunication

Multicolor Histochemical Staining for Identification of Mineralized and Non-Mineralized Musculoskeletal Tissue: Immunohistochemical and Radiological Validation in Decalcified Bone Samples

by Yu Sun, Heike Helmholz and Regine Willumeit-Römer

Bioengineering 2022, 9(10), 488; https://doi.org/10.3390/bioengineering9100488 - 21 Sep 2022

Cited by 3 | Viewed by 2876

Abstract

Histochemical staining of paraffin-embedded decalcified bone samples is commonly used in preclinical research of musculoskeletal diseases, enabling the visualization of multiple tissue components by the application of chromogens. The purpose of this study was to introduce a novel multicolor staining protocol involving optimized [...] Read more.

Histochemical staining of paraffin-embedded decalcified bone samples is commonly used in preclinical research of musculoskeletal diseases, enabling the visualization of multiple tissue components by the application of chromogens. The purpose of this study was to introduce a novel multicolor staining protocol involving optimized chemical reagents and procedure, allowing the identification of high-mineralized bone, low-mineralized fracture callus, cartilage and skeletal muscle fibers simultaneously. Fractured femur and healthy tail vertebra samples from adult male Sprague–Dawley rats were decalcified with EDTA and formic acid, respectively, followed by paraffin embedding, tissue sectioning and multicolor staining. Conventional Movat’s pentachrome and safranin O / fast green staining were conducted in parallel for comparison. Immunohistochemical staining of collagen type-X and micro-CT analysis were included to further validate the efficacy of the staining method. The multicolor staining allowed visualization of major musculoskeletal tissue components in both types of decalcified samples, providing quality outcomes with fewer chemical reagents and simplified procedures. Immunohistochemical staining demonstrated its capacity for identification of the endochondral ossification process during fracture healing. Micro-CT imaging validated the staining outcome for high-mineralized skeletal tissue. The application of the multicolor staining may facilitate future preclinical research involving decalcified paraffin-embedded samples. Full article

(This article belongs to the Special Issue Advances in Fracture Healing Research)

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9 pages, 1356 KiB

Open AccessArticle

Contribution to the 3R Principle: Description of a Specimen-Specific Finite Element Model Simulating 3-Point-Bending Tests in Mouse Tibiae

by Xiaowei Huang, Andreas K. Nussler, Marie K. Reumann, Peter Augat, Maximilian M. Menger, Ahmed Ghallab, Jan G. Hengstler, Tina Histing and Sabrina Ehnert

Bioengineering 2022, 9(8), 337; https://doi.org/10.3390/bioengineering9080337 - 25 Jul 2022

Cited by 2 | Viewed by 2434

Abstract

Bone mechanical properties are classically determined by biomechanical tests, which normally destroy the bones and disable further histological or molecular analyses. Thus, obtaining biomechanical data from bone usually requires an additional group of animals within the experimental setup. Finite element models (FEMs) may [...] Read more.

Bone mechanical properties are classically determined by biomechanical tests, which normally destroy the bones and disable further histological or molecular analyses. Thus, obtaining biomechanical data from bone usually requires an additional group of animals within the experimental setup. Finite element models (FEMs) may non-invasively and non-destructively simulate mechanical characteristics based on material properties. The present study aimed to establish and validate an FEM to predict the mechanical properties of mice tibiae. The FEM was established based on µCT (micro-Computed Tomography) data of 16 mouse tibiae. For validating the FEM, simulated parameters were compared to biomechanical data obtained from 3-point bending tests of the identical bones. The simulated and the measured parameters correlated well for bending stiffness (R² = 0.9104, p < 0.0001) and yield displacement (R² = 0.9003, p < 0.0001). The FEM has the advantage that it preserves the bones’ integrity, which can then be used for other analytical methods. By eliminating the need for an additional group of animals for biomechanical tests, the established FEM can contribute to reducing the number of research animals in studies focusing on bone biomechanics. This is especially true when in vivo µCT data can be utilized where multiple bone scans can be performed with the same animal at different time points. Thus, by partially replacing biomechanical experiments, FEM simulations may reduce the overall number of animals required for an experimental setup investigating bone biomechanics, which supports the 3R (replace, reduce, and refine) principle. Full article

(This article belongs to the Special Issue Advances in Fracture Healing Research)

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13 pages, 3678 KiB

Open AccessArticle

Establishment of an In Vitro Scab Model for Investigating Different Phases of Wound Healing

by Chao Liu, Helen Rinderknecht, Tina Histing, Jonas Kolbenschlag, Andreas K. Nussler and Sabrina Ehnert

Bioengineering 2022, 9(5), 191; https://doi.org/10.3390/bioengineering9050191 - 28 Apr 2022

Cited by 9 | Viewed by 3111

Abstract

Chronic wounds are a serious problem in clinical work and a heavy burden for individuals and society. In order to develop novel therapies, adequate model systems for the investigation of wound healing are required. Although in past years different in vitro and in [...] Read more.

Chronic wounds are a serious problem in clinical work and a heavy burden for individuals and society. In order to develop novel therapies, adequate model systems for the investigation of wound healing are required. Although in past years different in vitro and in vitro wound healing models have been established, a true human-like model does still not exist. Animal models are limited in their use due to species-specific differences in the skin, a lengthy manufacturing process, experimental costs, and ethical concerns. Both 2D and 3D in vitro models are usually comprised of only one or two skin cell types and fail to capture the reaction between blood cells and skin cells. Thus, our aim was to develop an in vitro scab model to investigate early reactions in the wound healing process. The here established scab model is comprised of HaCaT cells and freshly collected blood from healthy volunteers. The generated scabs were stably cultured for more than 2 weeks. TGF-β signaling is well known to regulate the early phases of wound healing. All three TGF-β isoforms and target genes involved in extracellular matrix composition and degradation were expressed in the in vitro scabs. To validate the in vitro scab model, the effects of either additional stimulation or the inhibition of the TGF-β signaling pathway were investigated. Exogenous application of TGF-β1 stimulated matrix remodeling, which loosened the structure of the in vitro scabs with time, also induced expression of the inhibitory Smad7. Inhibition of the endogenous TGF-β signaling, on the contrary, resulted in a rapid condensation and degranulation of the in vitro scabs. In summary, the here established in vitro scab model can be used to analyze the first phases of wound healing where blood and skin cells interact, as it is viable and responsive for more than 2 weeks. Full article

(This article belongs to the Special Issue Advances in Fracture Healing Research)

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18 pages, 1829 KiB

Open AccessReview

Advances in Animal Models for Studying Bone Fracture Healing

by Hui Gao, Jinming Huang, Quan Wei and Chengqi He

Bioengineering 2023, 10(2), 201; https://doi.org/10.3390/bioengineering10020201 - 3 Feb 2023

Cited by 20 | Viewed by 5373

Abstract

Fracture is a common traumatic injury that is mostly caused by traffic accidents, falls, and falls from height. Fracture healing is a long-term and complex process, and the mode of repair and rate of healing are influenced by a variety of factors. The [...] Read more.

Fracture is a common traumatic injury that is mostly caused by traffic accidents, falls, and falls from height. Fracture healing is a long-term and complex process, and the mode of repair and rate of healing are influenced by a variety of factors. The prevention, treatment, and rehabilitation of fractures are issues that urgently need to be addressed. The preparation of the right animal model can accurately simulate the occurrence of fractures, identify and observe normal and abnormal healing processes, study disease mechanisms, and optimize and develop specific treatment methods. We summarize the current status of fracture healing research, the characteristics of different animal models and the modeling methods for different fracture types, analyze their advantages and disadvantages, and provide a reference basis for basic experimental fracture modeling. Full article

(This article belongs to the Special Issue Advances in Fracture Healing Research)

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18 pages, 1334 KiB

Open AccessReview

Bone Healing Gone Wrong: Pathological Fracture Healing and Non-Unions—Overview of Basic and Clinical Aspects and Systematic Review of Risk Factors

by Dominik Saul, Maximilian M. Menger, Sabrina Ehnert, Andreas K. Nüssler, Tina Histing and Matthias W. Laschke

Bioengineering 2023, 10(1), 85; https://doi.org/10.3390/bioengineering10010085 - 9 Jan 2023

Cited by 20 | Viewed by 7801

Abstract

Bone healing is a multifarious process involving mesenchymal stem cells, osteoprogenitor cells, macrophages, osteoblasts and -clasts, and chondrocytes to restore the osseous tissue. Particularly in long bones including the tibia, clavicle, humerus and femur, this process fails in 2–10% of all fractures, with [...] Read more.

Bone healing is a multifarious process involving mesenchymal stem cells, osteoprogenitor cells, macrophages, osteoblasts and -clasts, and chondrocytes to restore the osseous tissue. Particularly in long bones including the tibia, clavicle, humerus and femur, this process fails in 2–10% of all fractures, with devastating effects for the patient and the healthcare system. Underlying reasons for this failure are manifold, from lack of biomechanical stability to impaired biological host conditions and wound-immanent intricacies. In this review, we describe the cellular components involved in impaired bone healing and how they interfere with the delicately orchestrated processes of bone repair and formation. We subsequently outline and weigh the risk factors for the development of non-unions that have been established in the literature. Therapeutic prospects are illustrated and put into clinical perspective, before the applicability of biomarkers is finally discussed. Full article

(This article belongs to the Special Issue Advances in Fracture Healing Research)

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