Osteogenic organoid for bone regeneration: Healing of bone defect in congenital pseudoarthrosis of the tibia.

Abstract

Congenital pseudoarthrosis of the tibia (CPT) is an uncommon disease associated with failure to achieve bone union and recurrent fractures. There is evidence showing that CPT is associated with decreased osteogenesis. Based on the capacity of mesenchymal stromal cells (MSCs) to induce osteogenesis, we develop an osteogenic organoid (OstO) constituted by these cells, and other components of the bone niche, for inducing bone formation in a child diagnosed with CPT. To evaluate the capacity of an OstO to induce bone formation in a patient with CPT. The OstO was fabricated with allogeneic bone marrow MSCs from a healthy donor, collagen microbeads (CM) and PRP clot. The CM and PRP function as extracellular matrix and scaffolds for MSC. The OstO was placed at the site of non-union. Internal and external fixation was placed in the tibia. Radiological evaluation was performed after MSCs transplantation. After 4 months of MSCs transplantation, radiographic imaging showed evidence of osteogenesis at the site of CPT lesion. The tibia showed bone consolidation and complete healing of the non-union CPT lesion after 6 months. Functional improvement was observed after 1 year of MSC transplantation. The OstO is a bone-like niche which promote osteogenesis in patients with failure in bone formation, such as CPT. To our knowledge, these results provide the first evidence showing CPT healing induced by an OstO constituted by allogeneic MSCs. Future studies incorporating a larger number of patients may confirm these results.