Although one can donate a kidney to another person without harm to oneself, people don’t really come with spare parts. Substantial tissue loss can result from different causes including cancer, injury and infection – and reconstructive surgery is then needed to try to repair the damage.
At present, the clinical “gold standard” in the field of reconstructive surgery is the autograft – taking harvesting tissue from one part of the patient’s body and transferring it to the damaged site. For example, to reconstruct the lower jaw, surgeons may harvest a portion of the fibula bone, together with the soft tissue and blood vessels around it, from the patient’s leg. The soft tissue and blood vessels are necessary for the bone to survive in its new location.
Of course, there are significant disadvantages to taking a large chunk out of one’s body, such as considerable pain or all the usual complications associated with a surgery at the donor site. Scientists are thus looking for alternatives to tissue harvest and moving towards tissue engineering.
Although some progress has been made in the field, there are still major problems to overcome in the search for tissue replacements – and one idea is de novo tissue generation. Instead of taking tissues from one part of the body to implant in another, new tissues for implantation would be grown in a lab.
That is where Prof. Shulamit Levenberg and her team in the Faculty of Biomedical Engineering at the Technion-Israel Institute of Technology come in. The focus of her tissue regeneration lab has been on the formation of complex blood vessel networks in lab-grown tissues.
Recently, her team created soft tissues with blood vessels for implantation using stem cells derived from the dental pulp – the soft tissue inside the tooth – together with capillary-forming endothelial cells. Adding the dental pulp stem cells promoted the generation of the blood vessels, eventually leading to enhanced tissue remodeling and repair. Using these methods, her team was able to promote regeneration of spinal cord injuries in rats. They published their work in the journal Advanced Healthcare Materials journal under the title “Engineered Vascularized Flaps, Composed of Polymeric Soft Tissue and Live Bone, Repair Complex Tibial Defects.”
Dr. Idan Redenski and his colleagues in Levenberg’s lab were able to tackle the challenge of implanting bone as part of reconstructive surgery so there would be soft tissues to support it and blood vessels to feed it. The team put together their own vascularized tissue technology with biological bone implants developed at Columbia University by Prof. Gordana Vunjak-Novakovic to create a de novo tissue flap containing live bone supported by vascularized soft tissue. This took the concept of implantable bone tissue to a whole different level.
After demonstrating that a mixed tissue flap can be grown, the team went on to use the new methodology to repair a bone defect in rats using a two-step approach. First, an engineered soft tissue flap was implanted. Once it was integrated into the body of the rat, the engineered flap was exposed in a second operation and used to repair a bone defect, while being supported by major blood vessels next to the defect site.
The decellularized bone was exposed and inserted to correct the existing defect while the engineered tissue flap supported it. The results were a complete success – the soft tissue with the blood vessels supporting and feeding the bone led to bridging of the bony defect, with the rat’s cells growing in and replenishing the implant. It was, in fact, a complete recovery, better than anything reconstructive surgery can achieve and not based on taking tissue from the patient.
Levenberg, Redenski and their colleagues hope that one day, it will be possible for a patient to receive a lab-grown bone perfectly matching the shape of his face, surrounded by lab-grown soft tissues based on their own cells cultivated on three-dimensional biomaterials. No major damage to other parts of the patient’s body would be necessary.
Redenski will soon begin a residency in oral and maxillofacial surgery at the Galilee Medical Centre, where he plans to continue his research with the hope of taking the methods developed in Levenberg’s lab and implementing them in the clinic.