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用于骨组织工程的杂交支架:负载 hDPSCs 的复合材料和生物活性水凝胶的整合。

Hybrid scaffolds for bone tissue engineering: Integration of composites and bioactive hydrogels loaded with hDPSCs.

机构信息

Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal; Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal; Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), Lisboa, Portugal.

Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal; Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal; Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), Lisboa, Portugal; Instituto Universitário de Ciências da Saúde (CESPU), Avenida Central de Gandra 1317, Gandra, 4585-116 Paredes, Portugal.

出版信息

Biomater Adv. 2025 Jan;166:214042. doi: 10.1016/j.bioadv.2024.214042. Epub 2024 Sep 12.

Abstract

Bone tissue regeneration remains a significant challenge in clinical settings due to the complexity of replicating the mechanical and biological properties of bone environment. This study addresses this challenge by proposing a hybrid scaffold designed to enhance both bioactivity and physical stability for bone tissue regeneration. This research is the fisrt to develop a rigid 3D structure composed of polycaprolactone (PCL) and hydroxyapatite nanoparticles (nHA) integrated with a bioink containing human dental pulp stem/stromal cells (hDPSCs), alginate, nHA and collagen (Col). The biofabricated constructs were extensively characterized through cytocompatibility tests, osteogenic differentiation assessment, and biocompatibility evaluation in a rat model. In vitro results demontrated that the hybrid scaffolds presented significantly higher cell viability after 168 h compared to the control group. Furthermore, the hybrid scaffolds showed increased osteogenic differentiation relative to other groups. In vivo evaluation indicated good biocompatibility, characterized by minimal inflammatory response and successful tissue integration. These findings highlight the scaffold's potential to support bone tissue regeneration by combining the mechanical strength of PCL and nHA with the biological activity of the alginate-nHA-Col and hDPSCs bioink. The current study provides a promising foundation for the development of biomaterials aimed at improving clinical outcomes in bone repair and regeneration, particulary for the treatment of critical-size bone defects, targeted drug administration, and three-dimensional models for bone tissue engineering.

摘要

由于骨环境的机械和生物特性复杂,骨组织再生在临床环境中仍然是一个重大挑战。本研究通过提出一种旨在增强骨组织再生的生物活性和物理稳定性的混合支架来应对这一挑战。这项研究首次开发了一种由聚己内酯 (PCL) 和羟基磷灰石纳米粒子 (nHA) 组成的刚性 3D 结构,与含有人牙髓干细胞/基质细胞 (hDPSCs)、藻酸盐、nHA 和胶原蛋白 (Col) 的生物墨水相结合。通过细胞相容性试验、成骨分化评估以及大鼠模型中的生物相容性评价对生物制造的构建体进行了广泛的表征。体外结果表明,与对照组相比,杂交支架在 168 小时后表现出明显更高的细胞活力。此外,与其他组相比,杂交支架显示出增加的成骨分化。体内评价表明具有良好的生物相容性,其特征是炎症反应最小化和组织成功整合。这些发现突出了支架通过将 PCL 和 nHA 的机械强度与藻酸盐-nHA-Col 和 hDPSCs 生物墨水的生物活性相结合来支持骨组织再生的潜力。本研究为开发旨在改善骨修复和再生临床结果的生物材料提供了有希望的基础,特别是用于治疗临界尺寸骨缺损、靶向药物给药和骨组织工程的三维模型。

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