Bone Tissue Engineering
Musculoskeletal therapies are not only a concern of the aging population, but also for the increased rate of sports injuries in the US. There are at least 500,000 surgical procedures performed every year in the US that require bone substitutes. The current gold standard for bone substitute is autografts. However, medical professionals are seeking alternative solutions because of several limiting factors such as donor site morbidity, doubled operational costs and low rate of success in aging patients.
Bone Tissue Engineering Scaffolds (BTES) provided hope to replace autografts during the last half century, but lack of understanding of the complex interactions between the host tissue and BTES slowed the process to replace autografts with BTES. This led bioengineers to reverse the problem of tissue engineering and focus more on the fundamental building principles of tissue development, creating a new field of regenerative engineering.
Fibrous scaffolds have proven success for tissue engineering applications, however the molecular mechanisms for the success of fibrous scaffolds limited researchers to build more targeted and controlled scaffolds for desired patient outcome. The Musculoskeletal Regenerative Engineering Lab at Penn State has been working on completing the puzzle pieces at the cell scaffold interface since 2010, generating a toolbox for musculoskeletal therapies. The main focus of Dr. Justin L. Brown, assistant professor of bioengineering, and his group is to develop a global model for mesencymal stem cells and fibrous scaffolds using molecular and cellular biological tools for musculoskeletal therapies. In the lab, the cellular bioengineering branch focuses more on dissecting the molecular players acting on cellular sensing of nano and micro-curvatures provided by different diameters of fibrous scaffolds. His group recently reported that Rho GTPases play pivotal roles in curvature sensing and osteogenesis, which acts as cellular mechanotransmitters. Also, the functional scaffold engineering branch of the lab aims on generating inductive scaffold architectures for regenerative engineering applications.
Another compelling study led by Dr. Jian Yang is through citrate presenting materials for non-union bone fractures. Dr. Yang's Transformative Biomaterials and Biotechnology Lab is developing citrate-based biodegradable polymers that innately induce bone stem cell differentiation and promote bone regeneration through a previously unexplored citrate mechanism. Animal studies have shown that the implants made of Dr. Yang's citrate polymers fully integrate with the surrounding bone tissues without eliciting the typical chronic inflammation caused by conventional synthetic implants. Based on these new biomaterials, Dr. Yang's lab is working on biodegradable orthopedic fixation devices such as bone screws, pins, and plates that have potentials for clinical translation. Dr. Yang is also in collaboration with Dr. Brown at University Park and Dr. Armstrong at Hershey Orthopedic Research Institute to understand the molecular mechanisms for citrate based skeletal regenerative therapies.
Delivery of growth factors or nanometer size bone inducing agents is also of interest for regenerative therapies. A recent report from bioengineering researchers at Penn State suggests mechanical forces regulate the internalization of such nanoparticles in extracellular space. Therefore Drs. Justin Brown and Sulin Zhang are working towards understanding the mechanisms regulating cellular internalization of nanoparticles on cells growing on fibrous scaffolds. The study will shed some light on growth factor delivery mechanisms for drug loaded bone tissue engineering scaffolds.
- Tugba Ozdemir, PhD candidate