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Unraveling the Mysteries of Tissue Engineering

New Generation of Dental and Maxillofacial Implants

“While implant osseointegration was discovered in the 20th century, the 21st century will be remembered as the era of osseointegration engineering,” explains Takahiro Ogawa, D.D.S., Ph.D., Assistant Professor of Advanced Prosthodontics and a Principal Investigator at the Weintraub Center. Dr. Ogawa’s research team applies research methods of molecular biology and nanotechnology for not only understanding the biology behind the osseointegration process, but also accelerating and enhancing the quality of the implant to bone attachment. His team has recently demonstrated that titanium implants may be encapsulated with a shell of mineralized tissue that is harder than normal bone. While bone wound healing is an integral process of successful osseointegration, this previously unreported biological activity may be directly involved in bone and implant integration. Dr. Ogawa is developing a new series of investigations aiming to uncover this process, which may in the near future provide the basis for osseointegration engineering.

Biomimetic Strategies to Regenerate Lost Tissues

Benjamin Wu, D.D.S., Ph.D., is Vice Chair of the Department of Bioengineering, with joint appointments in the Department of Materials Science and Engineering, and the School of Dentistry. Benefiting from his unique perspective as a practicing prosthodontist and bioengineer, his research applies modern bioengineering tools to solve clinical problems. Specifically, his lab aims to 1) learn how nature heals wounds and tissue defects; 2) copy nature and engineer biomimetic microenvironments to promote repair; and 3) investigate the molecular mechanisms by which progenitor cells interact with engineered microenvironments. His team recently reported in Nature Biotechnology that microenvironment alone, without the addition of expensive and exotic biochemicals, can stimulate adipose-derived and marrow-derived progenitor cells to differentiate into bone-forming cells and restore large, critical-size bony defects. This novel finding has motivated intense efforts to establish the molecular understanding by which minute changes in microenvironment regulate cell fate. Other exciting biomimetic strategies involves the engineering of an optimal microenvironment to deliver proteins that are naturally expressed during human bone formation; and the engineering of biomimetic surfaces to facilitate spinal cord repair. His biomimetic approach, coupled with modern bioengineering tools and molecular techniques, are fundamentally important in many cutting-edge disciplines, and is reflected by Prof. Wu’s active roles as Co-Director of the Weintraub Center, Member of the Brain Research Institute, and Affiliate of the California NanoSystems Institute.
 

Patients with head and neck cancer are often treated with surgery, which can leave complex oral and facial defects resulting from the removal of multiple layers of tissues. The long-term research goal of Ichiro Nishimura, D.D.S., D.M.Sc., D.M.D., Professor of Advanced Prosthodontics, is to apply molecular biotechnology and tissue engineering techniques in order to implement new reconstructive and regenerative treatments for patients with these defects to promote optimal wound healing. Fully differentiated adult tissues contain a small population of less differentiated stem cells. These adult stem cells may be redirected to express various useful phenotypes for tissue regeneration. Dr. Nishimura’s current research projects address the new genetic factors responsible for the molecular differentiation mechanism for adult tissue regeneration. A novel therapeutic gene transfer technology has been designed in the laboratory and is currently undergoing the initial validation process for its application to various adult tissues, including peripheral nerves, bone, skin and mucosa. The molecular biotechnologies developed in Dr. Nishimura’s laboratory will also be directly applicable to this advanced genome-based diagnostic system for the treatment of chronic and debilitating conditions such as osteoporosis, syndromic neuralgia, facial growth discrepancy and wound tissue contraction, and will be further developed for guided wound healing and ultimately facial tissue engineering.

Advances in Oral Sensory and Motor Function Research

Surgical manipulation of oral and maxillofacial tissues, from simple implant placement to large tumor removal, often results in the loss of sensory neuron activity. Neal Garrett, Ph.D., Associate Professor of Advanced Prosthodontics and Director of the Weintraub Center, has begun to uncover the accumulated dataset from his large NIH-funded clinical study on patients’ functional recovery after being rehabilitated with a maxillofacial prosthesis postsurgically. The data appear to suggest that the loss of sensory nerve activity represents an independent factor, which contributes to poor oral sensory and motor functional recovery.  His study has shown that patients who have maintained their sensory neuron activity after surgery perform markedly better than those who have lost oral sensation. The quality of patient’s life may be significantly increased if the sensory neuron activity is regained. Hiroshi Egusa, D.D.S., Ph.D. Weintraub Center Postdoctoral Visiting Scholar, in collaboration with Chia-Chien Wang, Ph.D., Postdoctoral Scholar, in the laboratory of Dr. Ichiro Nishimura, has undergone the challenge to differentiate bone marrow stem cells to neurons.  After an extensive series of trials, they found that stem cells extended an axon-like cell extension, showing a formation of synapses with a distant cell. By inserting a small electrode device through the cell membrane and measuring the voltage-gated ion channel, it was discovered that these cells were able to develop characteristics similar to neurons, and showed a clinical potential to induce neuronal cells from bone marrow stem cells.  This research hopes to be the platform by which prosthodontists will be able to replace not only teeth but also the sensory neurons associated with them.

Discovering the Beneficial Properties of Denture Resins

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