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.
Highlights
A large number of elderlies suffer from bone diseases that are associated with bone resorption and low ability of bone remodeling
As fibroblasts can be obtained from a small piece of biopsy sample of a patient without any invasive procedure[17] and expanded into an enough large number[18,19], our procedure may be quite adequate for preparation of a large number of autologous osteoblasts with a high bone forming ability
Confocal laser scanning microscope (CLSM) imaging of rhodamine-labeled NanoCliP and NanoCliP-FD gel revealed that the former had interconnected pores of several hundred micrometers in diameter, while the pores in the latter irregularly interlinked into larger pores (Fig. 1b and Supporting Information Table S1)
Summary
A large number of elderlies suffer from bone diseases that are associated with bone resorption and low ability of bone remodeling. Autologous bone graft has been performed to treat a patient with severe bone loss, but the preparation of a sufficient amount of bone for transplantation may cause adverse events such as pain in the patients at the sacrificed donor site[3] In this context, an efficient regenerative therapy to treat bone loss and bone resorption disorders is strongly needed. To realize an effective regenerative therapy for bone diseases, it is important to build a three-dimensional bone tissue in culture by combining two elements: (i) a 3D scaffold that could be built in a tailor-made manner to have the specific size and shape of the bone loss lesion in each patient, and (ii) a considerable number of autologous osteoblasts with a high bone forming ability. As fibroblasts can be obtained from a small piece of biopsy sample of a patient without any invasive procedure[17] and expanded into an enough large number[18,19], our procedure may be quite adequate for preparation of a large number of autologous osteoblasts with a high bone forming ability
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