scholarly journals Longitudinal in vivo micro-CT-based approach allows spatio-temporal characterization of fracture healing patterns and assessment of biomaterials in mouse femur defect models

2020 ◽  
Author(s):  
Esther Wehrle ◽  
Duncan C Tourolle né Betts ◽  
Gisela A Kuhn ◽  
Erica Floreani ◽  
Malavika H Nambiar ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Healing Process ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Collagen Scaffolds ◽  
Non Union ◽  
Spatio Temporal ◽  
Large Bone

AbstractThorough preclinical evaluation of novel biomaterials for treatment of large bone defects is essential prior to clinical application. Using in vivo micro-computed tomography (micro-CT) and mouse femoral defect models with different defect sizes, we were able to detect spatio-temporal healing patterns indicative of physiological and impaired healing in three defect sub-volumes and the adjacent cortex. The time-lapsed in vivo micro-CT-based approach was then applied to evaluate the bone regeneration potential of biomaterials using collagen and BMP-2 as test materials. Both collagen and BMP-2 treatment led to distinct changes in bone turnover in the different healing phases. Despite increased periosteal bone formation, 87.5% of the defects treated with collagen scaffolds resulted in non-unions. Additional BMP-2 application significantly accelerated the healing process and increased the union rate to 100%. This study further shows potential of time-lapsed in vivo micro-CT for capturing spatio-temporal deviations preceding non-union formation and how this can be prevented by application of biomaterials.This study therefore supports the application of longitudinal in vivo micro-CT for discrimination of normal and disturbed healing patterns and for the spatio-temporal characterization of the bone regeneration capacity of biomaterials.

scholarly journals Spatio-temporal characterization of fracture healing patterns and assessment of biomaterials by time-lapsed in vivo micro-computed tomography

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Esther Wehrle ◽  
Duncan C. Tourolle né Betts ◽  
Gisela A. Kuhn ◽  
Erica Floreani ◽  
Malavika H. Nambiar ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Bone Regeneration ◽  
Healing Process ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Collagen Scaffolds ◽  
Non Union ◽  
Spatio Temporal

AbstractThorough preclinical evaluation of functionalized biomaterials for treatment of large bone defects is essential prior to clinical application. Using in vivo micro-computed tomography (micro-CT) and mouse femoral defect models with different defect sizes, we were able to detect spatio-temporal healing patterns indicative of physiological and impaired healing in three defect sub-volumes and the adjacent cortex. The time-lapsed in vivo micro-CT-based approach was then applied to evaluate the bone regeneration potential of functionalized biomaterials using collagen and bone morphogenetic protein (BMP-2). Both collagen and BMP-2 treatment led to distinct changes in bone turnover in the different healing phases. Despite increased periosteal bone formation, 87.5% of the defects treated with collagen scaffolds resulted in non-unions. Additional BMP-2 application significantly accelerated the healing process and increased the union rate to 100%. This study further shows potential of time-lapsed in vivo micro-CT for capturing spatio-temporal deviations preceding non-union formation and how this can be prevented by application of functionalized biomaterials. This study therefore supports the application of longitudinal in vivo micro-CT for discrimination of normal and disturbed healing patterns and for the spatio-temporal characterization of the bone regeneration capacity of functionalized biomaterials.

scholarly journals Evaluation of longitudinal time-lapsedin vivomicro-CT for monitoring fracture healing in mouse femur defect models

2019 ◽  
Author(s):  
Esther Wehrle ◽  
Duncan C Tourolle né Betts ◽  
Gisela A Kuhn ◽  
Ariane C Scheuren ◽  
Sandra Hofmann ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Radiation Effects ◽  
Callus Formation ◽  
Healing Process ◽  
Fracture Repair ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Healing Phase ◽  
Longitudinal Imaging

AbstractLongitudinalin vivomicro-computed tomography (micro-CT) is of interest to non-invasively capture the healing process of individual animals in preclinical fracture healing studies. However, it is not known whether longitudinal imaging itself has an impact on callus formation and remodeling. In this study, a scan group received weekly micro-CT measurements (week 0-6), whereas controls were only scanned post-operatively and at week 5 and 6. Registration of consecutive scans using a branching scheme (bridged vs. unbridged defect) combined with a two-threshold approach enabled assessment of localized bone turnover and mineralization kinetics relevant for monitoring callus remodeling. Weekly micro-CT application did not significantly change any of the assessed callus parameters in the defect and periosteal volumes. This was supported by histomorphometry showing only small amounts of cartilage residuals in both groups, indicating progression towards the end of the healing period. Also, immunohistochemical staining of Sclerostin, previously associated with mediating adverse radiation effects on bone, did not reveal differences between groups.The established longitudinalin vivomicro-CT-based approach allows monitoring of healing phases in mouse femur defect models without significant effects of anesthesia, handling and radiation on callus properties. Therefore, this study supports application of longitudinalin vivomicro-CT for healing-phase-specific monitoring of fracture repair in mice.

scholarly journals Evaluation of longitudinal time-lapsed in vivo micro-CT for monitoring fracture healing in mouse femur defect models

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Esther Wehrle ◽  
Duncan C. Tourolle né Betts ◽  
Gisela A. Kuhn ◽  
Ariane C. Scheuren ◽  
Sandra Hofmann ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Radiation Effects ◽  
Callus Formation ◽  
Healing Process ◽  
Fracture Repair ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Healing Phase ◽  
Longitudinal Imaging

AbstractLongitudinal in vivo micro-computed tomography (micro-CT) is of interest to non-invasively capture the healing process of individual animals in preclinical fracture healing studies. However, it is not known whether longitudinal imaging itself has an impact on callus formation and remodeling. In this study, a scan group received weekly micro-CT measurements (week 0–6), whereas controls were only scanned post-operatively and at week 5 and 6. Registration of consecutive scans using a branching scheme (bridged vs. unbridged defect) combined with a two-threshold approach enabled assessment of localized bone turnover and mineralization kinetics relevant for monitoring callus remodeling. Weekly micro-CT application did not significantly change any of the assessed callus parameters in the defect and periosteal volumes. This was supported by histomorphometry showing only small amounts of cartilage residuals in both groups, indicating progression towards the end of the healing period. Also, immunohistochemical staining of Sclerostin, previously associated with mediating adverse radiation effects on bone, did not reveal differences between groups. The established longitudinal in vivo micro-CT-based approach allows monitoring of healing phases in mouse femur defect models without significant effects of anesthesia, handling and radiation on callus properties. Therefore, this study supports application of longitudinal in vivo micro-CT for healing-phase-specific monitoring of fracture repair in mice.

Decellularized bone extracellular matrix in skeletal tissue engineering

2020 ◽  
Vol 48 (3) ◽  
pp. 755-764
Author(s):  
Benjamin B. Rothrauff ◽  
Rocky S. Tuan
Keyword(s):  
Tissue Engineering ◽  
Bone Regeneration ◽  
Tissue Regeneration ◽  
Animal Studies ◽  
Tumor Resection ◽  
Regenerative Capacity ◽  
Skeletal Tissue ◽  
Large Bone

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.

scholarly journals Micro-Computed Tomography Analysis of Subchondral Bone Regeneration Using Osteochondral Scaffolds in an Ovine Condyle Model

2021 ◽  
Vol 11 (3) ◽  
pp. 891
Author(s):  
Taylor Flaherty ◽  
Maryam Tamaddon ◽  
Chaozong Liu
Keyword(s):  
Computed Tomography ◽  
Bone Regeneration ◽  
Subchondral Bone ◽  
Volume Ratio ◽  
Bone Volume ◽  
Osteochondral Defects ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Trabecular Thickness ◽  
Osteochondral Scaffold

Osteochondral scaffold technology has emerged as a promising therapy for repairing osteochondral defects. Recent research suggests that seeding osteochondral scaffolds with bone marrow concentrate (BMC) may enhance tissue regeneration. To examine this hypothesis, this study examined subchondral bone regeneration in scaffolds with and without BMC. Ovine stifle condyle models were used for the in vivo study. Two scaffold systems (8 mm diameter and 10 mm thick) with and without BMC were implanted into the femoral condyle, and the tissues were retrieved after six months. The retrieved femoral condyles (with scaffold in) were examined using micro-computed tomography scans (micro-CT), and the micro-CT data were further analysed by ImageJ with respect to trabecular thickness, bone volume to total volume ratio (BV/TV) ratio, and degree of anisotropy of bone. Statistical analysis compared bone regeneration between scaffold groups and sub-set regions. These results were mostly insignificant (p < 0.05), with the exception of bone volume to total volume ratio when comparing scaffold composition and sub-set region. Additional trends in the data were observed. These results suggest that the scaffold composition and addition of BMC did not significantly affect bone regeneration in osteochondral defects after six months. However, this research provides data which may guide the development of future treatments.

scholarly journals Longitudinal in vivo evaluation of bone regeneration by combined measurement of multi-pinhole SPECT and micro-CT for tissue engineering

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Philipp S. Lienemann ◽  
Stéphanie Metzger ◽  
Anna-Sofia Kiveliö ◽  
Alain Blanc ◽  
Panagiota Papageorgiou ◽  
...  
Keyword(s):  
Computed Tomography ◽  
High Resolution ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Bone Defects ◽  
Histological Evaluation ◽  
Biological Processes ◽  
Micro Ct ◽  
Pinhole Spect

Abstract Over the last decades, great strides were made in the development of novel implants for the treatment of bone defects. The increasing versatility and complexity of these implant designs request for concurrent advances in means to assess in vivo the course of induced bone formation in preclinical models. Since its discovery, micro-computed tomography (micro-CT) has excelled as powerful high-resolution technique for non-invasive assessment of newly formed bone tissue. However, micro-CT fails to provide spatiotemporal information on biological processes ongoing during bone regeneration. Conversely, due to the versatile applicability and cost-effectiveness, single photon emission computed tomography (SPECT) would be an ideal technique for assessing such biological processes with high sensitivity and for nuclear imaging comparably high resolution (<1 mm). Herein, we employ modular designed poly(ethylene glycol)-based hydrogels that release bone morphogenetic protein to guide the healing of critical sized calvarial bone defects. By combined in vivo longitudinal multi-pinhole SPECT and micro-CT evaluations we determine the spatiotemporal course of bone formation and remodeling within this synthetic hydrogel implant. End point evaluations by high resolution micro-CT and histological evaluation confirm the value of this approach to follow and optimize bone-inducing biomaterials.

scholarly journals Bone Regeneration Capacity of Newly Developed Uncalcined/Unsintered Hydroxyapatite and Poly-l-lactide-co-glycolide Sheet in Maxillofacial Surgery: An In Vivo Study

Nanomaterials ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 22
Author(s):  
Huy Xuan Ngo ◽  
Quang Ngoc Dong ◽  
Yunpeng Bai ◽  
Jingjing Sha ◽  
Shinji Ishizuka ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Reconstructive Surgery ◽  
Early Stage ◽  
Maxillofacial Surgery ◽  
Male Rats ◽  
Regeneration Ability ◽  
Sprague Dawley ◽  
Micro Computed Tomography ◽  
Rat Mandible

Uncalcined/unsintered hydroxyapatite and poly-l-lactide-co-glycolide (u-HA/PLLA/PGA) is a new bioresorbable nanomaterial with superior characteristics compared with current bioresorbable materials, including appropriate mechanical properties, outstanding bioactive/osteoconductive features, and remarkably shorter resorption time. Nevertheless, the bone regeneration characteristics of this nanomaterial have not been evaluated in maxillofacial reconstructive surgery. In this study, we used a rat mandible model to assess the bone regeneration ability of u-HA/PLLA/PGA material, compared with uncalcined/unsintered hydroxyapatite and poly-l-lactide acid (u-HA/PLLA) material, which has demonstrated excellent bone regenerative ability. A 4-mm-diameter defect was created at the mandibular angle area in 28 Sprague Dawley male rats. The rats were divided into three groups: u-HA/PLLA/PGA (u-HA/PLLA/PGA graft + defect), u-HA/PLLA (u-HA/PLLA graft + defect), and sham control (defect alone). At 1, 3, 8, and 16 weeks after surgeries, the rats were sacrificed and assessed by micro-computed tomography, histological analysis with hematoxylin and eosin staining, and immunohistochemical analyses. The results confirmed that the accelerated bone bioactive/regenerative osteoconduction of u-HA/PLLA/PGA was comparable with that of u-HA/PLLA in the rat mandible model. Furthermore, this new regenerative nanomaterial was able to more rapidly induce bone formation in the early stage and had great potential for further clinical applications in maxillofacial reconstructive surgery.

Strategies for inclusion of growth factors into 3D printed bone grafts

2021 ◽  
Author(s):  
Alessia Longoni ◽  
Jun Li ◽  
Gabriella C.J. Lindberg ◽  
Jelena Rnjak-Kovacina ◽  
Lyn M. Wise ◽  
...  
Keyword(s):  
Growth Factors ◽  
Bone Regeneration ◽  
New Technologies ◽  
Healing Process ◽  
Bone Grafts ◽  
Biological Properties ◽  
3 Dimensional ◽  
3D Printed ◽  
Physical And Chemical ◽  
Large Bone

Abstract There remains a critical need to develop new technologies and materials that can meet the demands of treating large bone defects. The advancement of 3-dimensional (3D) printing technologies has allowed the creation of personalized and customized bone grafts, with specific control in both macro- and micro-architecture, and desired mechanical properties. Nevertheless, the biomaterials used for the production of these bone grafts often possess poor biological properties. The incorporation of growth factors (GFs), which are the natural orchestrators of the physiological healing process, into 3D printed bone grafts, represents a promising strategy to achieve the bioactivity required to enhance bone regeneration. In this review, the possible strategies used to incorporate GFs to 3D printed constructs are presented with a specific focus on bone regeneration. In particular, the strengths and limitations of different methods, such as physical and chemical cross-linking, which are currently used to incorporate GFs to the engineered constructs are critically reviewed. Different strategies used to present one or more GFs to achieve simultaneous angiogenesis and vasculogenesis for enhanced bone regeneration are also covered in this review. In addition, the possibility of combining several manufacturing approaches to fabricate hybrid constructs, which better mimic the complexity of biological niches, is presented. Finally, the clinical relevance of these approaches and the future steps that should be taken are discussed.

scholarly journals In vivo bone regeneration assessment of offset and gradient melt electrowritten (MEW) PCL scaffolds

2020 ◽  
Vol 24 (1) ◽  
Author(s):  
Naghmeh Abbasi ◽  
Ryan S. B. Lee ◽  
Saso Ivanovski ◽  
Robert M. Love ◽  
Stephen Hamlet
Keyword(s):  
Bone Regeneration ◽  
Size Structure ◽  
Three Dimensional ◽  
Immunohistochemical Analysis ◽  
Repair Process ◽  
Micro Computed Tomography ◽  
Calvarial Defects ◽  
Promising Solution ◽  
Poly Caprolactone

Abstract Background Biomaterial-based bone tissue engineering represents a promising solution to overcome reduced residual bone volume. It has been previously demonstrated that gradient and offset architectures of three-dimensional melt electrowritten poly-caprolactone (PCL) scaffolds could successfully direct osteoblast cells differentiation toward an osteogenic lineage, resulting in mineralization. The aim of this study was therefore to evaluate the in vivo osteoconductive capacity of PCL scaffolds with these different architectures. Methods Five different calcium phosphate (CaP) coated melt electrowritten PCL pore sized scaffolds: 250 μm and 500 μm, 500 μm with 50% fibre offset (offset.50.50), tri layer gradient 250–500-750 μm (grad.250top) and 750–500-250 μm (grad.750top) were implanted into rodent critical-sized calvarial defects. Empty defects were used as a control. After 4 and 8 weeks of healing, the new bone was assessed by micro-computed tomography and immunohistochemistry. Results Significantly more newly formed bone was shown in the grad.250top scaffold 8 weeks post-implantation. Histological investigation also showed that soft tissue was replaced with newly formed bone and fully covered the grad.250top scaffold. While, the bone healing did not happen completely in the 250 μm, offset.50.50 scaffolds and blank calvaria defects following 8 weeks of implantation. Immunohistochemical analysis showed the expression of osteogenic markers was present in all scaffold groups at both time points. The mineralization marker Osteocalcin was detected with the highest intensity in the grad.250top and 500 μm scaffolds. Moreover, the expression of the endothelial markers showed that robust angiogenesis was involved in the repair process. Conclusions These results suggest that the gradient pore size structure provides superior conditions for bone regeneration.

scholarly journals A novel MRI compatible mouse fracture model to characterize and monitor bone regeneration and tissue composition

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Nina Schmitz ◽  
Melanie Timmen ◽  
Katharina Kostka ◽  
Verena Hoerr ◽  
Christian Schwarz ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Bone Regeneration ◽  
Cell Attachment ◽  
Healing Process ◽  
Living Organism ◽  
Fracture Site ◽  
Tissue Composition ◽  
Metal Implants ◽  
Callus Tissues

Abstract Over the last years, murine in vivo magnetic resonance imaging (MRI) contributed to a new understanding of tissue composition, regeneration and diseases. Due to artefacts generated by the currently used metal implants, MRI is limited in fracture healing research so far. In this study, we investigated a novel MRI-compatible, ceramic intramedullary fracture implant during bone regeneration in mice. Three-point-bending revealed a higher stiffness of the ceramic material compared to the metal implants. Electron microscopy displayed a rough surface of the ceramic implant that was comparable to standard metal devices and allowed cell attachment and growth of osteoblastic cells. MicroCT-imaging illustrated the development of the callus around the fracture site indicating a regular progressing healing process when using the novel implant. In MRI, different callus tissues and the implant could clearly be distinguished from each other without any artefacts. Monitoring fracture healing using MRI-compatible implants will improve our knowledge of callus tissue regeneration by 3D insights longitudinal in the same living organism, which might also help to reduce the consumption of animals for future fracture healing studies, significantly. Finally, this study may be translated into clinical application to improve our knowledge about human bone regeneration.

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