Nanogel tectonic porous 3D scaffold for direct reprogramming fibroblasts into osteoblasts and bone regeneration

Abstract

Transplantation of engineered three-dimensional (3D) bone tissue may provide therapeutic benefits to patients with various bone diseases. To achieve this goal, appropriate 3D scaffolds and cells are required. In the present study, we devised a novel nanogel tectonic material for artificial 3D scaffold, namely the nanogel-cross-linked porous (NanoCliP)-freeze-dried (FD) gel, and estimated its potential as a 3D scaffold for bone tissue engineering. As the osteoblasts, directly converted osteoblasts (dOBs) were used, because a large number of highly functional osteoblasts could be induced from fibroblasts that can be collected from patients with a minimally invasive procedure. The NanoCliP-FD gel was highly porous, and fibronectin coating of the gel allowed efficient adhesion of the dOBs, so that the cells occupied the almost entire surface of the walls of the pores after culturing for 7 days. The dOBs massively produced calcified bone matrix, and the culture could be continued for at least 28 days. The NanoCliP-FD gel with dOBs remarkably promoted bone regeneration in vivo after having been grafted to bone defect lesions that were artificially created in mice. The present findings suggest that the combination of the NanoCliP-FD gel and dOBs may provide a feasible therapeutic modality for bone diseases.

In Vivo Regeneration of Large Bone Defects by Cross-Linked Porous Hydrogel: A Pilot Study in Mice Combining Micro Tomography, Histological Analyses, Raman Spectroscopy and Synchrotron Infrared Imaging

“…Using the procedure described in previous reports [ 13 , 14 , 15 ], a coat of fibronectin was applied to the scaffolds to stimulate cellular adhesion. This was done as follows: we obtained fibronectin solution (Wako Laboratory Chemicals, Osaka, Japan), and the NanoCliP-FD matrix was soaked in the fibronectin solution for 6 h. It was then rinsed twice in ethanol and dried.…”

“…In this research, we investigated the performance of NanoCliP-FD gel [ 13 , 14 , 15 ] functionalized by fibronectin and used as a scaffold carrier for KUSA-A1 mesenchymal cells. The samples were tested for three weeks in vivo on an adult murine model.…”

Potential Applications of Advanced Nano/Hydrogels in Biomedicine: Static, Dynamic, Multi‐Stage, and Bioinspired

“…[145] 3D bone tissue scaffolds capable of delivering bone-derived cells could be a novel therapeutic approach to repair bone damage or disease. [146] The biomaterials need to be capable of localizing the cells at the site of the defect and also to drive osteogenic differentiation. [147] Sato et al designed a nanogel suitable for transplantation in mice bearing artificially induced bone defect lesions.…”

Advancement of Nanobiomaterials to Deliver Natural Compounds for Tissue Engineering Applications

“…The fibronectin-loaded nanogel-based 3D scaffolds showed positive outcomes in bone regeneration therapy. The biocompatibility and porous structure of the nanogels allowed the osteoblast cells to effectively adhere to the scaffold surface and contact to the loaded fibronectin [128].…”