Engineering fibroblast with reprogramming and spheronization for bone defect repair

Area of Science:

• Regenerative Medicine
• Biomaterials Engineering
• Cellular Reprogramming

Background:

• Bone diseases cause significant disability, particularly in the elderly.
• Osteoblasts are crucial for bone formation, but their function declines with age.
• Current cell-based therapies for bone defects are limited.

Purpose of the Study:

• To develop a method for engineering functional osteoblasts from fibroblasts for bone defect repair.
• To create novel osteoblastic living materials for enhanced bone regeneration.
• To address age-related dysfunction in osteoblasts for effective clinical application.

Main Methods:

• Fibroblast reprogramming using small molecules targeting the WNT signaling pathway.
• Optimization of temporal small molecule regulation for efficient osteoblast induction.
• Spheronization of induced osteoblasts to create transplantable tissue spheroids (iOB-Sps).

Main Results:

• Successfully generated healthy induced osteoblasts (iOBs) with functional osteoblastic traits.
• iOB-Sps demonstrated improved survival, self-bone formation, and reduced oxidative stress in vivo.
• Accelerated endogenous osteogenesis and angiogenesis in bone defect models.
• Effective healing of bone defects, particularly in aged models.

Conclusions:

• Material-free iOB-Sps serve as self-scaffolding biofunctional constructs.
• This approach offers a promising strategy for clinical autologous bone defect repair.
• The method is effective across all age groups, including the elderly.