Acta Biomaterialia

Journal: Acta Biomaterialia

Abbreviation

Acta Biomater

Publisher

Elsevier

ISSN

1742-7061
1878-7568

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Publications 1 - 10 of 121

Light-curable polymer/calcium phosphate nanocomposite glue for bone defect treatment
Schneider, Oliver D.; Stepuk, Alexander; Mohn, Dirk; et al. (2010)
Acta Biomaterialia
How cosmetic tightening products modulate the biomechanics and morphology of human skin
Pensalfini, Marco; Rotach, M.; Hopf, Raoul; et al. (2020)
Acta Biomaterialia
The active and passive mechanical behavior of a cosmetic tightening product for skin anti-aging is investigated based on a wide range of in vivo and in vitro measurements. The experimental data are used to inform a numerical model of the attained cosmetic effect, which is then implemented in a commercial finite-element framework and used to analyze the mechanisms that regulate the biomechanical interaction between the native tissue and the tightening film. Such a film reduces wrinkles and enhances skin consistency by increasing its stiffness by 48-107% and reducing inelastic, non-recoverable deformations (−47%). The substrate deformability influences both the extent of tightening and the reduction of wrinkle amplitude. The present findings allow, for the first time, to rationalize the mechanisms of action of cosmetic products with a tightening action and provide quantitative evidence for further optimization of this fascinating class of biomaterials.
Culture of 3D bioprinted bone constructs requires an increased fluid dynamic stimulation
Mainardi, Valerio Luca; Rubert, Marina; Sabato, Claudia; et al. (2022)
Acta Biomaterialia
In vitro flow-induced mechanical stimulation of developing bone tissue constructs has been shown to favor mineral deposition in scaffolds seeded with cells directly exposed to the fluid flow. However, the effect of fluid dynamic parameters, such as shear stress (SS), within 3D bioprinted constructs is still unclear. Thus, this study aimed at correlating the SS levels and the mineral deposition in 3D bioprinted constructs, evaluating the possible dampening effect of the hydrogel. Human mesenchymal stem cells (hMSCs) were embedded in 3D bioprinted porous structures made of alginate and gelatin. 3D bioprinted constructs were cultured in an osteogenic medium assessing the influence of different flow rates (0, 0.7 and 7 ml/min) on calcium and collagen deposition through histology, and bone volume (BV) through micro-computed tomography. Uniform distribution of calcium and collagen was observed in all groups. Nevertheless, BV significantly increased in perfused groups as compared to static control, ranging from 0.35±0.28 mm3, 11.90±8.74 mm3 and 25.81±5.02 mm3 at week 3 to 2.28±0.78 mm3, 22.55±2.45 mm3 and 46.05±5.95 mm3 at week 6 in static, 0.7 and 7 ml/min groups, respectively. SS values on construct fibers in the range 10-100 mPa in 7 ml/min samples were twice as high as those in 0.7 ml/min samples showing the same trend of BV. The obtained results suggest that it is necessary to enhance the flow-induced mechanical stimulation of cell-embedding hydrogels to increase the amount of mineral deposited by hMSCs, compared to what is generally reported for the development of in vitro bone constructs. Statement of significance: In this study, we evaluated for the first time how the hydrogel structure dampens the effect of flow-induced mechanical stimulation during the culture of 3D bioprinted bone tissue constructs. By combining computational and experimental techniques we demonstrated that those shear stress thresholds generally considered for culturing cells seeded on scaffold surface, are no longer applicable when cells are embedded in 3D bioprinted constructs. Significantly, more bone volume was formed in constructs exposed to shear stress values generally considered as detrimental than in constructs exposed shear stress values generally considered as beneficial after 3 weeks and 6 weeks of dynamic culture using a perfusion bioreactor.
Modulating biomechanical and integrating biochemical cues to foster adaptive remodeling of tissue engineered matrices for cardiovascular implants
Breitenstein, Pascal; Visser, Valery L.; Motta, Sarah E.; et al. (2025)
Acta Biomaterialia
Cardiovascular disease remains one of the leading causes of mortality in the Western world. Congenital heart disease affects nearly 1 % of newborns, with approximately one-fourth requiring reconstructive surgery during their lifetime. Current cardiovascular replacement options have significant limitations. Their inability to grow poses particular challenges for pediatric patients. Tissue Engineered Matrix (TEM)-based in situ constructs, with their self-repair and growth potential, offer a promising solution to overcome the limitations of current clinically used replacement options. Various functionalization strategies, involving the integration of biomechanical or biochemical components to enhance biocompatibility, have been developed for Tissue Engineered Vascular Grafts (TEVG) and Tissue Engineered Heart Valves (TEHV) to foster their capacity for in vivo remodeling. In this review, we present the current state of clinical translation for TEVG and TEHV, and provide a comprehensive overview of biomechanical and biochemical functionalization strategies for TEVG and TEHV. We discuss the rationale for functionalization, the implementation of functionalization cues in TEM-based TEVG and TEHV, and the interrelatedness of biomechanical and biochemical cues in the in vivo response. Finally, we address the challenges associated with functionalization and discuss how interdisciplinary research, especially when combined with in silico models, could enhance the translation of these strategies into clinical applications. Statement of significance: Cardiovascular disease remains one of the leading causes of mortality, with current replacements being unable to grow and regenerate. In this review, we present the current state of clinical translation for tissue engineered vascular grafts (TEVG) and heart valves (TEHV). Particularly, we discuss the rationale and implementation for functionalization cues in tissue engineered matrix-based TEVGs and TEHVs, and for the first time we introduce the interrelatedness of biomechanical and biochemical cues in the in-vivo response. These insights pave the way for next-generation cardiovascular implants that promise better durability, biocompatibility, and growth potential. Finally, we address the challenges associated with functionalization and discuss how interdisciplinary research, especially when combined with in silico models, could enhance the translation of these strategies into clinical applications.
Time-dependent mechanical behavior of human amnion
Mauri, Arabella; Perrini, Michela; Ehret, Alexander E.; et al. (2015)
Acta Biomaterialia
On the anisotropy of skeletal muscle tissue under compression
Böl, Markus; Ehret, Alexander E.; Leichsenring, Kay; et al. (2014)
Acta Biomaterialia
Mechanoregulation analysis of bone formation in tissue engineered constructs requires a volumetric method using time-lapsed micro-computed tomography
Griesbach, Julia K.; Schulte, Friederike A.; Schädli, Gian Nutal; et al. (2024)
Acta Biomaterialia
Bone can adapt its microstructure to mechanical loads through mechanoregulation of the (re)modeling process. This process has been investigated in vivo using time-lapsed micro-computed tomography (micro-CT) and micro-finite element (FE) analysis using surface-based methods, which are highly influenced by surface curvature. Consequently, when trying to investigate mechanoregulation in tissue engineered bone constructs, their concave surfaces make the detection of mechanoregulation impossible when using surface-based methods. In this study, we aimed at developing and applying a volumetric method to non-invasively quantify mechanoregulation of bone formation in tissue engineered bone constructs using micro-CT images and FE analysis. We first investigated hydroxyapatite scaffolds seeded with human mesenchymal stem cells that were incubated over 8 weeks with one mechanically loaded and one control group. Higher mechanoregulation of bone formation was measured in loaded samples with an area under the curve for the receiver operating curve (AUCformation) of 0.633–0.637 compared to non-loaded controls (AUCformation: 0.592–0.604) during culture in osteogenic medium (p < 0.05). Furthermore, we applied the method to an in vivo mouse study investigating the effect of loading frequencies on bone adaptation. The volumetric method detected differences in mechanoregulation of bone formation between loading conditions (p < 0.05). Mechanoregulation in bone formation was more pronounced (AUCformation: 0.609–0.642) compared to the surface-based method (AUCformation: 0.565–0.569, p < 0.05). Our results show that mechanoregulation of formation in bone tissue engineered constructs takes place and its extent can be quantified with a volumetric mechanoregulation method using time-lapsed micro-CT and FE analysis. Statement of significance: Many efforts have been directed towards optimizing bone scaffolds for tissue growth. However, the impact of the scaffolds mechanical environment on bone growth is still poorly understood, requiring accurate assessment of its mechanoregulation. Existing surface-based methods were unable to detect mechanoregulation in tissue engineered constructs, due to predominantly concave surfaces in scaffolds. We present a volumetric approach to enable the precise and non-invasive quantification and analysis of mechanoregulation in bone tissue engineered constructs by leveraging time-lapsed micro-CT imaging, image registration, and finite element analysis. The implications of this research extend to diverse experimental setups, encompassing culture conditions, and material optimization, and investigations into bone diseases, enabling a significant stride towards comprehensive advancements in bone tissue engineering and regenerative medicine.
Multi-omics qualification of an organ-on-a-chip model of osteolytic bone metastasis
Munoz Castro , Natalia; Nolan , Joanne; Maniati , Eleni; et al. (2026)
Acta Biomaterialia
Bone is a primary site for metastasis in breast cancer, with up to 70 % of patients with metastatic breast cancer developing osteolytic bone lesions, wherein cancer cells drive osteoclast resorption of bone. However, progress in developing therapies is limited by the absence of predictive in vitro models. This study developed a unique organ-on-a-chip model to simulate osteolytic bone metastasis and utilised a multi-omics approach for characterisation/qualification and validation against in vivo data. Using the Emulate S1 platform, we co-cultured murine osteocytes and osteoclasts to recreate the bone microenvironment, alongside breast cancer cells in a separate channel separated by a porous membrane. Using RNA sequencing, cytokine profiling, and fluorescence staining, we demonstrated the importance of the complete tri-culture model in replicating key aspects of in vivo biology, and uncovered critical pathways involved in metastasis. A synergistic effect was observed in the tri-culture organ-chip model, leading to increased cancer cell migration and the upregulation of pro-metastatic and pro-inflammatory pathways that promote bone degradation and cancer progression. This study validates an organ-chip model of osteolytic breast cancer bone metastasis as a scalable alternative to traditional animal models. Furthermore, we show how multi-omics and bioinformatics techniques may be used for qualification and validation of organ-chip models; for unpicking the relative contribution of the different cell types; and to identify signalling pathways and therapeutic targets. Statement of significance In this study, we develop a 3D organ-on-a-chip tri-culture model of the osteolytic metastatic niche, in which we verify expected bone and breast cancer cell behaviours. Importantly, we successfully validate our organ-chip against a dataset from the gold standard in vivo preclinical model of osteolytic breast metastases, using transcriptomics and proteomics to confirm strong alignment of gene expression profiles with in vivo mouse expression. Additionally, our multi-omics analysis sheds new light on both expected and novel molecular pathways for therapeutic targeting, demonstrating the utility of the organ-chip as a potential replacement for preclinical mouse models of breast cancer metastases in bone. Therefore, this study represents a key marker in the field of organ-chip research, demonstrating the importance of biomaterials technologies for preclinical science. Most importantly, our work demonstrates for biotech and pharma companies that qualified organ-chip devices can play a role as intermediate medium-throughput technologies for screening lead drug candidates.
Towards refining microstructures of biodegradable magnesium alloy WE43 by spark plasma sintering
Soderlind, Julie; Cihova, Martina; Schäublin, Robin; et al. (2019)
Acta Biomaterialia
On multiscale tension-compression asymmetry in skeletal muscle
Böl, Markus; Kohn, Stephan; Leichsenring, Kay; et al. (2022)
Acta Biomaterialia
Skeletal muscle tissue shows a clear asymmetry with regard to the passive stresses under tensile and compressive deformation, referred to as tension-compression asymmetry (TCA). The present study is the first one reporting on TCA at different length scales, associated with muscle tissue and muscle fibres, respectively. This allows for the first time the comparison of TCA between the tissue and one of its individual components, and thus to identify the length scale at which this phenomenon originates. Not only the passive stress-stretch characteristics were recorded, but also the volume changes during the axial tension and compression experiments. The study reveals clear differences in the characteristics of TCA between fibres and tissue. At tissue level TCA increases non-linearly with increasing deformation and the ratio of tensile to compressive stresses at the same magnitude of strain reaches a value of approximately 130 at 13.5% deformation. At fibre level instead it initially drops to a value of 6 and then rises again to a TCA of 14. At a deformation of 13.5%, the tensile stress is about 6 times higher. Thus, TCA is about 22 times more expressed at tissue than fibre scale. Moreover, the analysis of volume changes revealed little compressibility at tissue scale whereas at fibre level, especially under compressive stress, the volume decreases significantly. The data collected in this study suggests that the extracellular matrix has a distinct role in amplifying the TCA, and leads to more incompressible tissue behaviour. Statement of significance: This article analyses and compares for the first time the tension-compression asymmetry (TCA) displayed by skeletal muscle at tissue and fibre scale. In addition, the volume changes of tissue and fibre specimens with application of passive tensile and compressive loads are studied. The study identifies a key role of the extracellular matrix in establishing the mechanical response of skeletal muscle tissue: It contributes significantly to the passive stress, it is responsible for the major part of tissue-scale TCA and, most probably, prevents/balances the volume changes of muscle fibres during deformation. These new results thus shed light on the origin of TCA and provide new information to be used in microstructure-based approaches to model and simulate skeletal muscle tissue.

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