implantation-tissue-engineered-vascular-graft-mouse-carotid-artery

Implantation of Tissue-Engineered Vascular Graft in Mouse Carotid Artery <em>via</em> Cuff Technique

The development of small-diameter vascular grafts has been a global endeavor, with numerous research groups contributing to this field. Animal ...

Tiangong University

Chinese Academy of Medical Sciences and Peking Union Medical College

Fish swim bladder-derived biomaterials are prospective cardiovascular materials due to anti-calcification, adequate mechanical properties, and good biocompatibility. However, their immunogenic safety profile, which primarily determines their feasibility as medical devices in clinical practice, remains unknown. Herein, the immunogenicity of glutaraldehyde crosslinked fish swim bladder (Bladder-GA) and un-crosslinked swim bladder (Bladder-UN) samples was examined using  and  assays according to ISO 10993-20. The  splenocyte proliferation assay showed that cell growth was lower in the extract medium of Bladder-UN and Bladder-GA, compared to the LPS-or Con A-treated group. Similar results were obtained in  assays. In the subcutaneous implantation model, the thymus coefficient, spleen coefficient and ratio of immune cell subtypes showed no significant difference between the bladder groups and the sham group. In terms of the humoral immune response, the total IgM concentration was lower in the Bladder-GA and Bladder-UN groups (988 ± 238 μg ml and 1095 ± 296 μg ml, respectively) than that in the sham group (1329 ± 132 μg ml) at 7 days. The total IgG concentrations were 422 ± 78 μg ml in Bladder-GA and 469 ± 172 μg ml in Bladder-UN at 30 days, which were slightly higher than that in the sham group (276 ± 95 μg ml) but there was no significant difference compared with Bovine-GA (468 ± 172 μg ml), indicating that these materials did not elicit a strong humoral immune response. Systemic immune response-related cytokines and C-reactive protein were stable during implantation, while IL-4 levels increased with time. The classical foreign body response was not observed around all the implants, and the ratio of CD163+/iNOS macrophages in Bladder-GA and Bladder-UN was higher than that in the Bovine-GA group at the implanted site at 7 and 30 days. Finally, no organ toxicity was observed in any of the groups. Collectively, the swim bladder-derived material did not elicit significant aberrant immune responses , giving strong confidence for its application in tissue engineering or medical devices. Furthermore, more dedicated research on immunogenic safety assessment in large animal models is encouraged to facilitate the clinical practice of swim bladder-derived materials.

Immunogenicity assessment of swim bladder-derived biomaterials.

The unique ability of piezoelectric materials to generate electricity spontaneously has attracted widespread interest in the medical field. In addition to the ability to convert mechanical stress into electrical energy, piezoelectric materials offer the advantages of high sensitivity, stability, accuracy and low power consumption. Because of these characteristics, they are widely applied in devices such as sensors, controllers and actuators. However, piezoelectric materials also show great potential for the medical manufacturing of artificial organs and for tissue regeneration and repair applications. For example, the use of piezoelectric materials in cochlear implants, cardiac pacemakers and other equipment may help to restore body function. Moreover, recent studies have shown that electrical signals play key roles in promoting tissue regeneration. In this context, the application of electrical signals generated by piezoelectric materials in processes such as bone healing, nerve regeneration and skin repair has become a prospective strategy. By mimicking the natural bioelectrical environment, piezoelectric materials can stimulate cell proliferation, differentiation and connection, thereby accelerating the process of self-repair in the body. However, many challenges remain to be overcome before these concepts can be applied in clinical practice, including material selection, biocompatibility and equipment design. On the basis of the principle of electrical signal regulation, this article reviews the definition, mechanism of action, classification, preparation and current biomedical applications of piezoelectric materials and discusses opportunities and challenges for their future clinical translation.

From electricity to vitality: the emerging use of piezoelectric materials in tissue regeneration.

Macrophages are primary immune cells that play a crucial role in tissue regeneration during the early stages of biomaterial implantation. They create a microenvironment that facilitates cell infiltration, angiogenesis, and tissue remodeling. In the field of vascular tissue engineering, numerous studies have been conducted to modulate the macrophage phenotype by designing various biomaterials, which in turn enhances the regenerative capacity and long-term patency of vascular grafts. However, the mechanism underlying the different phenotypes of macrophages involved in the tissue regeneration of vascular grafts remains unclear. In this study, vascular grafts loaded with various macrophage phenotypes were developed, and their effects were evaluated both in vivo and in vitro. The RAW 264.7 macrophages (M0) were initially treated with LPS or IL-4/IL-10 and polarized into M1 and M2 phenotypes. Subsequently, M0, M1, and M2 macrophages were seeded onto electrospun PCL scaffolds to obtain macrophage-loaded vascular grafts (PCL-M0, PCL-M1, and PCL-M2). As prepared vascular grafts were implanted into the mouse carotid artery for up to one month. The results indicate that the loading of M2 macrophages effectively enhances the patency rate and neotissue formation of vascular grafts. This is achieved through the development of a well-defined endothelium and smooth muscle layer. RNA sequencing was used to investigate the mechanisms of action of different macrophages on tissue regeneration. The study found that M1 macrophages inhibited tissue regeneration by mediating angiogenesis and chronic inflammation through upregulation of VEGFa, IL-1β, and IL-6 expression. In contrast, M2 macrophages regulate the immune microenvironment by upregulating the expression of IL-4 and TGF-β, thereby promoting tissue regeneration. In conclusion, our study demonstrates how different macrophage phenotypes contribute to the initial inflammatory microenvironment surrounding vascular grafts, thereby modulating the biological process of vascular remodeling. STATEMENT OF SIGNIFICANCE: Regulating the biophysical and biochemical characteristics of biomaterials can induce macrophage polarization and enhance vascular remodeling. In previous work, we fabricated a vascular graft with a macroporous structure that promoted macrophage infiltration and polarization into a pro-regenerative phenotype. To illustrate the mechanism, we established a new mouse model and evaluated the effects of different macrophages on vascular regeneration. The study revealed that tuning macrophage phenotype can impact the initial inflammatory microenvironment by secreting cytokines, which can increase the patency rate and regenerative capacity of vascular grafts. These findings provide essential theoretical support for the development of immunoregulatory scaffolds for vascular and other tissue regeneration.

Article	Year
Immunogenicity assessment of swim bladder-derived biomaterials. Biomaterials science\| PubMed ID: 36807688	2023
From electricity to vitality: the emerging use of piezoelectric materials in tissue regeneration. Burns & trauma\| PubMed ID: 38957661	2024
Tuning macrophage phenotype for enhancing patency rate and tissue regeneration of vascular grafts. Acta biomaterialia\| PubMed ID: 40158766	2025

Lili Song

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