A team from the New York Stem Cell Foundation (NYSCF) Research Institute reports the development of a novel bone engineering technique called Segmental Additive Tissue Engineering (SATE). The method (“Segmental Additive Tissue Engineering”), described in a paper in Scientific Reports, allows researchers to combine segments of bone engineered from stem cells to create large scale, personalized grafts that will improve treatment for those suffering from bone disease or injury through regenerative medicine, according to the scientists.

“Segmental bone defects caused by trauma and disease represent a major clinical problem worldwide. Current treatment options are limited and often associated with poor outcomes and severe complications. Bone engineering is a promising alternative solution, but a number of technical challenges must be addressed to allow for effective and reproducible construction of segmental grafts that meet the size and geometrical requirements needed for individual patients and routine clinical applications. It is important to devise engineering strategies and standard operating procedures that make it possible to scale up the size of bone-engineered grafts, minimize process and product variability, and facilitate technology transfer and implementation,” write the researchers.

“To address these issues, we have combined traditional and modular tissue engineering approaches in a strategy referred to as SATE. To demonstrate this approach, a digital reconstruction of a rabbit femoral defect was partitioned transversally to the longitudinal axis into segments (modules) with discoidal geometry and defined thickness to enable protocol standardization and effective tissue formation in vitro. Bone grafts corresponding to each segment were then engineered using biomimetic scaffolds seeded with human induced pluripotent stem cell-derived mesodermal progenitors (iPSC-MPs) and a novel perfusion bioreactor with universal design. The SATE strategy enables the effective and reproducible engineering of segmental bone grafts for personalized skeletal reconstruction, and will facilitate technology transfer and implementation of a tissue engineering approach to segmental bone defect therapy.”

“We are hopeful that SATE will one day be able to improve the lives of the millions of people suffering from bone injury due to trauma, cancer, osteoporosis, osteonecrosis, and other devastating conditions,” says Susan L. Solomon, NYSCF CEO. “Our goal is to help these patients return to normal life, and by leveraging the power of regenerative medicine, SATE brings us one step closer to reaching that goal.”

It’s estimated that over a million individuals per year will suffer from a fracture due to bone disease, and as people age, their bones get weaker, leading to complications later in life.

“Bone defects obtained in disease or injury are a growing issue, and having effective treatment options in place for personalized relief, no matter the severity of a patient’s condition, is of critical importance,” explains Giuseppe de Peppo, Ph.D., NYSCF – Ralph Lauren senior principal investigator who led the study.

Bone defects are currently treated with either synthetic substitutes or bone grafts taken from a bone bank or another part of the patient’s body. However, these treatments often spark immune rejection, do not form connective tissue or vasculature needed for functional bone, and can be quickly outgrown by pediatric patients, according to the scientists, who add that bone grafts generated from patient stem cells overcome such limitations, but it is difficult to bioengineer these grafts in the exact size and shape needed to treat large defects.

“As the size of the defect that needs to be replaced gets larger, it becomes harder to reproducibly create a graft that can move from the lab to the clinic,” says NYSCF researcher Martina Sladkova, Ph.D., the study’s first author. “We wanted to see if we could instead engineer smaller segments of bone individually and then combine them to create a graft that overcomes the current limitations in the size and shape of a bone that can be grown in the lab.”

To explore this question, the team engineered a graft corresponding to a defect in the femur of a rabbit that affected about 30% of the bone’s total volume. They first scanned the femur to assess the size and shape of the defect and generated a model of the graft. They then partitioned the model into smaller segments and created customized scaffolds for each.

The team then placed these scaffolds, fitted with human induced pluripotent stem cell-derived mesodermal progenitor cells, into a bioreactor specially designed to accommodate bone grafts with a broad range of sizes. This bioreactor was able to ensure uniform development of tissue throughout the graft, something that existing versions of bioreactors often struggle to do.

Once the cells are integrated and grown within the scaffold, the segments of the bone graft could then be combined into a single, mechanically stable graft using biocompatible bone adhesives or other orthopedic devices.

NYSCF officials say that SATE is standardized, versatile, and easy to implement, allowing for bioengineered bone grafts to more quickly make the leap from bench to bedside. The researchers believe in its potential to enable bone graft engineering that will help to improve the quality of life of pediatric and adult patients suffering from segmental bone defects.

 

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