Osaka University uses BMP2 mixed with nanoclay gels for high-quality bone regeneration

The protein BMP2 has excellent osteogenic potential and is used to accelerate bone union in non-union or delayed-union fractures and spinal fusion surgery in the United States and Europe. Because collagen is a major component of bone and has high biocompatibility, collagen sponge (CS) containing BMP2 is mainly used. However, it can cause a strong inflammatory reaction and bone formation in unintended places due to the release of BMP2 from CS to the surrounding area early after transplantation. A research group led by Graduate Student Takuya Furuichi (doctoral course), Specially Appointed Associate Professor Takashi Kaito, and Professor Seiji Okada at Osaka University Graduate School of Medicine, has found that the use of BMP2, a protein that promotes the formation of bone and cartilage, mixed with nanoclay (NC) gels during bone regeneration allows for high-quality regeneration with negligible inflammatory reaction. The material is expected to be a next-generation therapy for safe bone union. The study was published in Bioactive Materials.

The research group demonstrated the effectiveness of NC gel as a new-generation osteogenic material by showing that the use of NC, instead of CS, in combination with BMP2 allowed for the retention of BMP2 with negligible release to the surrounding environment, attenuation of BMP2-associated inflammatory response, and high-quality bone formation only where intended.

First, they examined the inflammatory response attenuating effect and the bone formation promoting effect by subfascial implantation of a mixture of NC and BMP2 in mice. When CS was used, inflammatory cells accumulated around the CS in a BMP2 dose-dependent manner, forming a thick inflammatory response layer. In contrast, inflammatory cells hardly accumulated when NC was used and were found only mildly inside the NC. Inflammation did not spill over to the surrounding area even when the BMP2 dose was increased.

The CS containing BMP2 induced the formation of unintended bone (ectopic ossification) outside the CS, with the interior of the new bone being spongy and filled with adipose tissue. When the NC containing BMP2 was used, a large amount of uniform cartilage was formed inside the NC and then replaced by bone, resulting in dense, strong bone packed tightly to the interior and formed only where intended.

In spinal fusion surgery in rats, a model of human spinal surgery, NC was confirmed to result in bone union with dense and strong bone. Additionally, cell-based experiments indicated that NCs facilitated the differentiation of cells into cartilage and bone while inhibiting the function of osteoclasts, which are responsible for bone resorption.

Furuichi said, "Pseudarthrosis (nonunion) and bone defects cause pain and limitation of movement for patients and are difficult to treat. BMP2 has attracted attention as a protein that potently promotes bone regeneration, but the risk of side effects has been a problem. The results of this study demonstrated the possibility of using BMP2 effectively and safely. We hope to realize regenerative medicine, with which patients' bones can heal quickly, and patients can return to an active life soon."

Journal Information
Publication: Bioactive Materials
Title: Nanoclay gels attenuate BMP2-associated inflammation and promote chondrogenesis to enhance BMP2-spinal fusion
DOI: 10.1016/j.bioactmat.2024.10.027