Quantitative evaluation of the <i>in vivo</i> biocompatibility and performance of freeze-cast tissue scaffolds

Divakar, Prajan; Moodie, Karen L; Demidenko, Eugene; Hoopes, P. Jack; Wegst, Ulrike G. K.

doi:10.1088/1748-605x/ab316a

Cited by 8 publications

(3 citation statements)

References 52 publications

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“…The design and functionalization of the scaffold impact the expression of the immune response produced after implantation, resulting in variations in the size of the capsule surrounding the biomaterial. The capsule size recorded in our investigation, as shown in Figure 5B, is smaller than that reported by other studies (Divakar et al, 2020), where a capsule thickness of 3 mm was observed around scaffolds made from unfunctionalized collagen. Results similar to those obtained in our investigation were also reported (Dulany et al, 2020;Camarero-Espinosa et al, 2022).…”

Section: Discussioncontrasting

confidence: 87%

In vivo biocompatibility testing of nanoparticle-functionalized alginate–chitosan scaffolds for tissue engineering applications

Viveros-Moreno,

Garcia-Lorenzana,

Peña-Mercado

et al. 2023

Front. Bioeng. Biotechnol.

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Background: There is a strong interest in designing new scaffolds for their potential application in tissue engineering and regenerative medicine. The incorporation of functionalization molecules can lead to the enhancement of scaffold properties, resulting in variations in scaffold compatibility. Therefore, the efficacy of the therapy could be compromised by the foreign body reaction triggered after implantation.Methods: In this study, the biocompatibilities of three scaffolds made from an alginate–chitosan combination and functionalized with gold nanoparticles (AuNp) and alginate-coated gold nanoparticles (AuNp + Alg) were evaluated in a subcutaneous implantation model in Wistar rats. Scaffolds and surrounding tissue were collected at 4-, 7- and 25-day postimplantation and processed for histological analysis and quantification of the expression of genes involved in angiogenesis, macrophage profile, and proinflammatory (IL-1β and TNFα) and anti-inflammatory (IL-4 and IL-10) cytokines.Results: Histological analysis showed a characteristic foreign body response that resolved 25 days postimplantation. The intensity of the reaction assessed through capsule thickness was similar among groups. Functionalizing the device with AuNp and AuNp + Alg decreased the expression of markers associated with cell death by apoptosis and polymorphonuclear leukocyte recruitment, suggesting increased compatibility with the host tissue. Similarly, the formation of many foreign body giant cells was prevented. Finally, an increased detection of alpha smooth muscle actin was observed, showing the angiogenic properties of the elaborated scaffolds.Conclusion: Our results show that the proposed scaffolds have improved biocompatibility and exhibit promising potential as biomaterials for elaborating tissue engineering constructs.

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Section: Discussioncontrasting

confidence: 87%

In vivo biocompatibility testing of nanoparticle-functionalized alginate–chitosan scaffolds for tissue engineering applications

Viveros-Moreno,

Garcia-Lorenzana,

Peña-Mercado

et al. 2023

Front. Bioeng. Biotechnol.

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“…An example for a biomedical application of chitosan-based tissue scaffolds are freeze-cast shell-only and core–shell conduits for peripheral nerve repair. − ,, In addition to the highly aligned porosity, the ridges in the pure chitosan scaffolds assist in neurite guidance. − The addition of CNF increases the scaffolds’ mechanical properties and through these the resilience, when handled and secured in place with a stitch or glue by a surgeon, for example. Additionally, the fibrillar pillars and bridges in the Chi–CNF help preserve the pore structure, also when laterally compressed during surgery and implantation; , similar structural benefits in freeze-cast scaffolds made from fibrillar components were observed in vivo for collagen …”

Section: Resultsmentioning

confidence: 80%

Plant-Derived Nanocellulose as Structural and Mechanical Reinforcement of Freeze-Cast Chitosan Scaffolds for Biomedical Applications

2019

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Despite considerable recent interest in microand nanofibrillated cellulose as constituents of lightweight structures and scaffolds for applications that range from thermal insulation to filtration, few systematic studies have been reported to date on structure−property-processing correlations in freeze-cast chitosan−nanocellulose composite scaffolds, in general, and their application in tissue regeneration, in particular. Reported in this study are the effects of the addition of plant-derived nanocellulose fibrils (CNF), crystals (CNCs), or a blend of the two (CNB) to the biopolymer chitosan on the structure and properties of the resulting composites. Chitosan−nanocellulose composite scaffolds were freeze-cast at 10 and 1 °C/min, and their microstructures were quantified in both the dry and fully hydrated states using scanning electron and confocal microscopy, respectively. The modulus, yield strength, and toughness (work to 60% strain) were determined in compression parallel and the modulus also perpendicular to the freezing direction to quantify anisotropy. Observed were the preferential alignments of CNCs and/or fibrils parallel to the freezing direction. Additionally, observed was the self-assembly of the nanocellulose into microstruts and microbridges between adjacent cell walls (lamellae), features that affected the mechanical properties of the scaffolds. When freeze-cast at 1 °C/min, chitosan−CNF scaffolds had the highest modulus, yield strength, toughness, and smallest anisotropy ratio, followed by chitosan and the composites made with the nanocellulose blend, and that with crystalline cellulose. These results illustrate that the nanocellulose additions homogenize the mechanical properties of the scaffold through cell-wall material self-assembly, on the one hand, and add architectural features such as bridges and pillars, on the other. The latter transfer loads and enable the scaffolds to resist deformation also perpendicular to the freezing direction. The observed property profile and the materials' proven biocompatibility highlight the promise of chitosan−nanocellulose composites for a large range of applications, including those for biomedical implants and devices.

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“…More recently, collagen was freeze cast to create scaffolds for permanent female sterilization that was tested on successfully with rats . The effect of processing conditions was further tested and showed that lower freezing rate produced larger pores and thicker lamellar walls, resulting in decreased modulus but higher yield strength . Across multiple materials, freeze casting has showed promise for creating controlled micro‐ and macroporosity.…”

Section: Bioinspired Designs At Different Length‐scalesmentioning

confidence: 99%

Multiscale Toughening Mechanisms in Biological Materials and Bioinspired Designs

et al. 2019

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Biological materials found in Nature such as nacre and bone are well recognized as light-weight, strong, and tough structural materials. The remarkable toughness and damage tolerance of such biological materials are conferred through hierarchical assembly of their multiscale (i.e., atomicto macroscale) architectures and components. Herein, the toughening mechanisms of different organisms at multilength scales are identified and summarized: macromolecular deformation, chemical bond breakage, and biomineral crystal imperfections at the atomic scale; biopolymer fibril reconfiguration/deformation and biomineral nanoparticle/nanoplatelet/ nanorod translation, and crack reorientation at the nanoscale; crack deflection and twisting by characteristic features such as tubules and lamellae at the microscale; and structure and morphology optimization at the macroscale. In addition, the actual loading conditions of the natural organisms are different, leading to energy dissipation occurring at different time scales. These toughening mechanisms are further illustrated by comparing the experimental results with computational modeling. Modeling methods at different length and time scales are reviewed. Examples of biomimetic designs that realize the multiscale toughening mechanisms in engineering materials are introduced. Indeed, there is still plenty of room mimicking the strong and tough biological designs at the multilength and time scale in Nature.

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Quantitative evaluation of the in vivo biocompatibility and performance of freeze-cast tissue scaffolds

Cited by 8 publications

References 52 publications

In vivo biocompatibility testing of nanoparticle-functionalized alginate–chitosan scaffolds for tissue engineering applications

In vivo biocompatibility testing of nanoparticle-functionalized alginate–chitosan scaffolds for tissue engineering applications

Plant-Derived Nanocellulose as Structural and Mechanical Reinforcement of Freeze-Cast Chitosan Scaffolds for Biomedical Applications

Multiscale Toughening Mechanisms in Biological Materials and Bioinspired Designs

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