New porous biomaterials may help in bone repair

Scientists at Nanyang Technological University (NTU Singapore) in Singapore have developed a new biomaterial made entirely from discarded bullfrog skins and fish scales that may help in bone repair.

A porous biomaterial containing the same compound that predominates in bone acts as a scaffold for bone-forming cells to attach and proliferate, leading to the formation of new bone.

Through laboratory experiments, the NTU Singapore team discovered that human bone-forming cells seeded on biomaterial scaffolds successfully attached and began to proliferate. This is a sign of growth. They also found that biomaterials have a low risk of causing an inflammatory response.

Such scaffolds can be used to help regenerate bone tissue lost due to illness or injury, such as jaw defects from trauma or cancer surgery. It can also help the bone grow around surgical implants such as dental implants.

Scientists believe that biomaterials are a promising alternative to current standard practices that use the patient’s own tissue, requiring additional surgery for bone extraction. At the same time, the production of this biomaterial addresses the issue of aquaculture waste, said Dalton Tei, assistant professor of the NTU Materials Science and Engineering Department (MSE), who led the interdisciplinary research.

Over 20 million tonnes of fishery by-products such as fins, scales and skins are discarded each year. In Singapore, the total annual consumption of frog meat and fish is estimated to be about 100 million kilograms, and bullfrog skin and fish scales are two of Singapore’s largest sidestreams of aquaculture waste.

Our research adopted a “waste-to-resource” approach, turning waste into high-value materials for biomedical applications and closing the waste loop of the process. Studies in our lab have shown that the biomaterials we designed may be a promising option for bone repair. The potential of this biomaterial is enormous, ranging from repairing bone defects due to injury and aging to dental applications for aesthetics. Our research is based on NTU’s series of work in the field of sustainability and is in line with Singapore’s circular economy approach towards a zero waste nation... “

Dalton Tay, Associate Professor, Nanyang Technological University

Professor Matthew Hu Xiao, co-author of the study and director of the Environmental Chemistry and Materials Center at the Nanyang Institute for Environmental Water Research (NEWRI), said: Treatment can reduce wastewater pollution. “

Goh Bee Tin, a clinical associate professor at the National University of Singapore, who was not involved in the study, said: “The National University of Singapore is excited to use bullfrog skin as a natural biomaterial for tissue regeneration. From gingival tissue regeneration in periodontal disease to bone and tumor surgery for dental implant placement. See many potential dental applications, down to the posterior gums. Eliminating the need for additional bone harvesting surgery saves time and money, and the patient. “

Survey results published online Materials Science and Engineering C It will be published in April and will be published in Volume 126 of the Journal in July.

The research team has applied for a patent for biomaterial wound healing and bone tissue engineering applications. The team is currently evaluating further long-term safety and Effectiveness of It is a biomaterial as a dental product funded by the China-Singapore International Joint Research Institute and aims to bring the waste-to-resource technology pipeline closer to commercialization.

Turn waste into treasure

The total annual consumption of frog meat and fish in Singapore is estimated at about 100 million kilograms, and bullfrog skin and fish scales are two of Singapore’s largest sidestreams of aquaculture waste. The fishery waste used by the NTU team was collected from Kaisenfish Farm and Jurong Frog Farm.

To make biomaterials, the team first extracted type 1 tropocollagen (many molecules form collagen fibers) from the abandoned skin of bullfrogs, cultivated locally and in large quantities in Singapore for consumption. Was imported to Singapore. Hydroxyapatite (calcium phosphate compound) from snakehead scales, commonly known as Toman fish.

Collagen and hydroxyapatite (HA) are the two major components found in bone, giving biomaterials the structure, composition, and ability to promote bone-like cell adhesion. These two components make the biomaterial strong.

Scientists removed all impurities from the bullfrog skin and blended it into a concentrated collagen paste diluted with water. Next, collagen was extracted from this mix. “Using this approach, we were able to obtain about 70% of the highest collagen yields ever reported from frog skin, making this approach commercially viable,” said NTU. Says Tay, an assistant professor at the Faculty of Biological Sciences. SBS).

HA was harvested by calcination (a refining process that requires high heat) to remove organic matter from discarded fish scales and then air dried.

HA powder was added to the extracted collagen to synthesize a biomaterial and poured into a mold to create a 3D porous scaffold. The entire process takes less than two weeks and we believe the team can further shorten and scale up.

Proof-of-concept experiment

To assess the biological performance of porous biomaterial scaffolds for bone repair, scientists seeded scaffolds with bone-forming cells.

In their laboratory experiments, they found a significant increase in the number of cells. After a week, the cells were evenly distributed throughout the scaffold. This indicates that scaffolding can promote proper cell activity and ultimately lead to tissue formation. Scientists have also found that the presence of HA in biomaterials significantly enhances bone formation.

Biomaterials have also been tested for their tendency to provoke an inflammatory response that is common after biomaterials have been transplanted into the body.

Scientists use a real-time polymerase chain reaction to expose endotoxin, a compound whose expression levels of pro-inflammatory genes in human immune cells exposed to biomaterials are known to stimulate the immune response. We found that it remained “relatively modest” when compared to the controls that were given. Professor Tay said.

For example, the expression of the gene IL6 in the biomaterials group was negligible, at least 50-fold lower than that of immune cells exposed to endotoxin. This suggests that the biomaterial developed by NTU has a low risk of causing an excessive acute inflammatory response.

Taken together, these findings show that scaffolding of biomaterials synthesized from discarded bullfrog skin and fish scales is a promising waste-to-resource bone graft alternative for bone repair and regeneration. Shows the possibility of.

Jurong Frog Farm Director, Chelsea One “The aquaculture industry is an important way to meet the growing global demand for safe, high-quality seafood, but the major challenges we face are the huge waste of precious fishery resources and downcycling. In Singapore, frog meat and fish are estimated to weigh about 100 million kilograms, and bullfrog skins and fish scales are two of the largest sidestreams of aquaculture waste here. Multiple seafood. Integrating waste streams into a single high-value product is a prime example of sustainable innovation in the aquaculture industry. “

Going forward, the research team will work with clinical and industrial partners in animal research to determine how tissues in the body react to this biomaterial in the long term, and the ability of materials to repair bone defects and skin scars. And bring the entire waste-to-resource technology pipeline closer to commercialization.