Bone & Tissue Engineering Research at NYSCF
Tissue Engineering News
The Context: Prosthetic implants are regularly used in dentistry and orthopedics, and there are an estimated 2 million Americans...
Scientists from the New York Stem Cell Foundation (NYSCF) Research Institute have developed a new bone engineering technique called...
Below are select publications outlining recent advancements in tissue engineering from NYSCF scientists.
Hypothermic and cryogenic preservation of tissue-engineered human bone
Tam E, McGrath M, Sladkova M, AlManaie A, Alostaad A, de Peppo GM. Annals of the New York Academy of Sciences. 2019 Oct 31. doi: 10.1111/nyas.14264.
This study finds that hypothermic preservation (storing at a few degrees above freezing) supports cell viability in stem-cell-derived bone grafts better than cryogenic preservation.
GMP-compatible and xeno-free cultivation of mesenchymal progenitors derived from human-induced pluripotent stem cells
McGrath M, Tam E, Sladkova M, AlManaie A, Zimmer M, de Peppo GM. Stem Cell Research and Therapy. DOI: 10.1186/s13287-018-1119-3.
The researchers found that mesenchymal progenitor cells grown in media free of animal-derived compounds are equally as viable as those grown in media containing a substance derived from cows. Mesenchymal progenitor cells have never been grown in media free of animal-derived compounds until this study.
Segmental Additive Tissue Engineering
Sladkova M, Alawadhi R, Alhaddad RJ, Esmael A, Alansari S, Saad M, Yousef JM, Alqaoud L, de Peppo GM.
Scientific Reports. 2018. DOI: 10.1038/s41598-018-29270-4.
In this study, researchers describe a technique for combining segments of bone engineered from stem cells to create large scale, personalized grafts that will enhance treatment for those suffering from bone disease or injury through regenerative medicine.
Comparison of Decellularized Cow and Human Bone for Engineering Bone Grafts with Human Induced Pluripotent Stem Cells
Sladkova M, Cheng J, Palmer M, Chen S, Lin C, Xia W, Yu YE, Zhou B, Engqvist H, de Peppo GM.
Tissue Engineering Part A. 2018. DOI: 10.1089/ten.tea.2018.0149.
In this study, NYSCF Research Institute scientists led by NYSCF – Ralph Lauren Senior Principal Investigator Giuseppe Maria de Peppo, PhD, identified a more effective and cost-efficient method for creating the scaffolds used to generate lab-grown bone using stem cells.
Engineering bone tissue substitutes from human induced pluripotent stem cells
de Peppo GM, Marcos-Campos I, Kahler DJ, Alsalman D, Shang L, Vunjak-Novakovic G, Marolt D.
Proceedings of the National Academy of Sciences of the United States of America. 2013. DOI: 10.1073/pnas.1301190110.
In a step towards personalized bone grafts to treat traumatic injury or congenital defects, this study, led by Darja Marolt, PhD, and Giuseppe Maria de Peppo, PhD, and published in the Proceedings of the National Academy of Sciences, reports the generation of patient-specific bone substitutes from skin cells for repair of large bone defects.
NYSCF’s Dr. Giuseppe Maria de Peppo and Dr. Martina Sladkova recently conducted an interview with RegMedNet about SATE, their pioneering method for combining segments of bone engineered from stem cells to create large scale, personalized grafts. Read the interview below.
After many years working in the field of tissue engineering, it has become evident that a number of different issues were limiting the ability to construct segmental bone grafts effectively and reproducibly. These include the inability to grow large tissue products ex vivo, the lack of standard operating procedures, the customization of bioreactor design each time the tissue geometry and size change, and other issues that impede technology transfer and implementation.
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.
On the other hand, the ability to use bone grafts grown from patient’s own cells could help overcoming these issues, which include limited bone transplant availability, risk of disease transmission, long recovery time, poor graft integration and remodeling, and biomaterial associated infections.
In the published study, we have used de-cellularized bovine bone scaffolds that were manufactured to the exact shape using a 5-axis milling machine. 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. 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.
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. Ex vivo and in vivo studies will help assessing the strength and stability of segmental bone grafts engineered using our approach.
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.
In a few words, the real challenge was to make simple something that is technically quite complicated, i.e. growing segmental bone grafts ex vivo. 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. I think I’d like to see more automation and scaling up in tissue engineering. 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.