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The Segmental Additive Tissue Engineering SATE strategy addresses all these issues and enables the construction of segmental bone grafts with geometrical requirements for individual patients that could facilitate a tissue engineering approach to segmental bone defect therapy. We are hopeful that this new strategy 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 of the skeletal system.

Management of segmental bone defects remains an important medical challenge, especially for pediatric patients with a developing skeleton. When people suffer from segmental bone defects a few treatment options exist. The type of treatment depends on the size of the defect, and generally involves the use of bone transplants, alloplastic materials and prosthetic implants. All these treatment options, however, present several disadvantages that can lead to severe health complications. We have used de-cellularized bovine bone because of its good mechanical properties which are important for segmental reconstruction in load bearing locations , and because of existing knowledge on its use in bone engineering applications.

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However, the use of synthetic biomaterials that can be manufactured in a reproducible fashion, rapidly and at an affordable cost is expected to foster translation of tissue-engineered bone grafts to the clinics. The scaffolds were seeded with mesodermal progenitors cells derived from human induced pluripotent stem cells generated via reprogramming of skin cells. These cells can be derived for any patient and can be manufactured to the numbers millions to trillions required for engineering large volume segmental bone grafts.

Following culture in the SATE bioreactor, the tissue-engineered bone segments modules could be combined into a single, mechanically stable graft using biocompatible bone adhesives or traditional reconstructive orthopedic devices. Unpublished data have demonstrated that cement-based bone adhesives can be used to piece the different bone segments together. Ongoing studies are now aimed at testing the mechanical stability of segmental grafts engineered using the SATE strategy for future animal studies, and potential clinical applications.

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I would not say that the two things can be compared at this point. However, partitioning of 3D reconstructions of segmental bone defects transversally to their longitudinal axis maximizes the structural capability of bone grafts engineering using the SATE strategy. The real challenge was to put together standard operating procedures that facilitate technology transfer and implementation. For example, one challenge was to come up with a simple universal design for the SATE bioreactor, a configuration suitable for generating segmental bone grafts with a broad range of sizes and geometries.

In addition, in order to reduce manufacturing time and allow production at an affordable cost, we had to come up with a design that was suitable for manufacturing the bioreactor using rapid prototyping technologies, in this case 3D printing. Another challenge was to develop a strategy to seed the cells efficiently and uniformly onto the scaffolds. This is very important to ensure reproducibility when growing bone grafts in the laboratory.

Tissue engineering: from lab to clinic | University College London

In a few words, the real challenge was to make simple something that is technically quite complicated, i. It is only this way that bioengineered bone grafts can make the leap from bench to bedside. The next step will be to test this approach in clinically-relevant models of segmental defects, and work in close collaboration with orthopedic surgeons to develop an effective surgical technique that leads to graft survival and integration.

In addition, development of adequate manufacturing and clinical procedures that meet international regulatory requirements, intelligent monitoring of the culture environment during tissue growth in bioreactors, prevention of microbial contamination using environmentally controlled areas clean rooms , process validation and quality control testing are some other most important challenges that must be addressed before segmental bone grafts engineered using the SATE strategy can be used to treat human patients.

Someday, the use of bone transplants and alloplastic materials for bone reconstructions might become a thing of the past. We could be able to grow patient-specific bone on-demand, and thus circumvent the complications associated with current treatments. Right now things are still done by hand, and finding ways to automate the process could really change the game. Equally important, development of culture conditions supporting the growth of multicellular bone grafts, which include a vascular system for example, will likely facilitate graft integration and survival, and thus boost the therapeutic potential of tissue-engineered products.

Beside their potential in reconstructive therapies, tissue-engineered bone grafts will be increasingly used as qualified models to study development and disease, and test drugs and biomaterials within a context that better reflects the native bone environment.

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What is the importance of tissue engineering? However, these treatments carry several complications: Current treatments may cause immune rejection or fail to integrate with surrounding connective tissues. Why use stem cells for tissue engineering? Tissue Engineering Part A, , 19 : p.


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Tissue engineering : from lab to clinic

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"Musculoskeletal Tissue Engineering " - Michael J. Yaszemski, MD, PhD