Research

The Department of Plastic Surgery's applied research lab is named Tissue Regeneration and Molecular Cell Engineering Lab or TRAMCEL. Multi- and Inter- disciplinary research is conducted by coupling a wide array of disciplines such as biomedical engineering, biophysics, and nanotechnology principals applied towards reconstructive plastic surgery. The following provides an overview of research highlights.

Regenerative Medicine and Tissue Engineering

Repairing and regenerating tissues damaged or resected due to cancer through the coupling of engineering, clinical science and life sciences. Focus areas are described as follows:

• Bone regeneration to repair mandible and midface defects resulting from head and neck cancer
• Adipose tissue engineering to repair soft tissue defects resulting from tumor resection and restore the breast mound following mastectomy and lumpectomy due to breast cancer
• Musculofascia regeneration to repair defects in the abdominal wall musculofascia
• Trachea tissue engineering to repair partial and circumferential tracheal defects resulting from head and neck cancer
• Tissue engineered regeneration of skin and epithelium and their application to tissue flap reconstruction

Nanomedicine and NanoTherapy

Repairing damaged tissues and treating and detecting cancer by developing medical interventions at the molecular scale that couples nanotechnology, clinical science and the life sciences. Focus areas are:

• Developing innovative delivery strategies to increase efficacy of delivered therapy via degradable and targeted nano-carriers and localizing delivery via tissue flap therapy
• Biocompatible quantum dots for in vivo imaging of vasculature
• Modulation of molecular events to control cell processes, such as angiogenesis, and bone regeneration, such as silencing RNA therapy
• In vivo guidance of micro-vasculature at the nanoscale. The ultimate goal is to develop or provide fully functional blood vessel networks within tissue engineered constructs and autologous tissue flaps and grafts

Engineered Biologics

Engineering design of novel natural, biologically derived or hybrid materials from the sub-molecular scale up to patient-specific geometry in order to control cell-material interactions, biomechanics, vascularization and the in vivo release of therapeutic agents, thereby engineering the process of regeneration for repair and reconstruction of cancer patients. Focus areas include:

• Development of biologically derived biopolymers to control degradation, remodeling and reformation of new viable tissues
• Novel therapeutic scaffolds for controlled delivery of anti-cancer agents and factors for tissue regeneration and repair
• Engineering self assembly of nano-structures in three-dimensions to provide molecular control per patient specific design

Computational Modeling

Application of data-analytical methods, mathematical modeling and computational simulation techniques to the design and optimization of three-dimensional tissue regenerative platform. This interdisciplinary research combines computational, theoretical and experimental biology, physiology, material science and engineering. Focus areas include engineering three-dimensional scaffolds, cellular response to microenvironment, and cellular and tissue biomechanics.

Funding

The funding for the research is actively obtained and maintained from various extramural sources such as the National Institutes of Health, National Institute on Aging, National Institute of Biomedical Imaging and Bioengineering, Musculoskeletal Transplant Foundation, Department of Defense, Gillson-Logenbaugh Foundation, Anderson Foundation and Kyte Fund.

Contact

Cynthia D. Branch-Brooks 
Laboratory Coordinator
Tissue Regeneration and Molecular Cell Engineering Labs (TRAMCEL)
Plastic Surgery - Research
Office Phone: 713-792-1831
Fax: 713-563-0231
E-mail: cbranch@mdanderson.org

The Department of Plastic Surgery's researchers are at the forefront of innovative development and evaluation of surgical and clinical strategies that improve standard of care. The diversity of technical challenges being addressed requires the cadre of researchers to conduct translational research across numerous disparate disciplines to create novel and cost-effective therapeutics, medical devices and clinical protocols for cancer-related deformities. The following provides an overview of research highlights:

Preoperative Planning

Integrating novel technologies and clinical experience to develop innovative patient-specific surgical planning tools. This research area couples clinical science, biomechanics, behavioral science, medical imaging, computer science and visualization. Current focus areas include midface and breast reconstruction.

Clinical Decision Support

Multi-media patient database archiving and management and effective logical data mining to provide surgeons multi-factorial knowledge content with which to make optimum surgical and clinical care decisions. This bioinformatics area of study is critical for designing and conducting meaningful retro and prospective clinical studies.

Surgical Strategies

Assessing standard and developing new strategies to overcome surgical limitations. Current research studies include:

• Developing and evaluating novel breast reconstruction techniques
• Elucidating factors that abrogate free flap viability and integrity
• Designing and optimizing biomaterials and their application to improve reconstruction
• Developing novel bone reconstruction techniques for pediatric cancer patients
• Assessing speech and swallowing function following oral/pharyngeal reconstruction
• Treating skin disorders with cryogenically-cooled lasers
• Restoring erectile function subsequent to prostate removal via nerve reconstruction
• Conducting sentinel lymph node biopsy for early detection of ocular tumors
• Assessing the effect of immuno- and molecular therapies on ocular tumors

Quantitative Metrics

Developing metrics and tools to objectively measure surgical, aesthetic, and functional outcomes. Technologies under development include defining metrics of breast aesthetics following reconstruction, quantitative visualization methods for midface bone defects and breast skin elasticity.

Transplantation of solid organs has become the standard of care for many life threatening medical circumstances. Composite tissue allotransplantation (CTA) is the transfer of a composite tissue that may include skin, muscle, bone and nerve. CTA promises to be a revolutionary advance in reconstructive surgery, affording a perfect "replacement part” for tissues compromised by disease or trauma. CTA has the potential to render better cosmetic and functional outcomes for reconstruction and avoid multiple, lengthy, and often morbid operations utilizing the patient’s own tissue. 

These techniques have been applied to the hand, face, abdominal wall, larynx and other body parts. Transplantation offers hope to those who suffer from severe disfigurement for an improved quality of life. It is the only operation that has the potential to restore near-normal appearance in patients with socially crippling facial injuries, and offer the most complete functional restoration currently available for hand amputees.

While appealing, human transplantation utilizing this approach presents many technical and medical challenges. The procedures can be costly; there is risk of rejection and sequelae from the use of immunosuppressant medications. As remarkable as the potential possibilities are for transplant recipients, there are many questions associated with the procedure. While the early outcomes appear promising, resulting in better aesthetic and functional outcomes when compared to traditional reconstructive techniques, long-term outcomes are still unclear. The ethics of facial transplantation in particular go beyond the life and death issues common to most transplant procedures and raise other issues that have not generally influenced medical decision-making processes.

Technical Challenges

The biggest hurdle for composite transplantation is overcoming immune modulation and the safe induction of tolerance to the composite tissue allograft (CTA). The necessity of immunosuppression and the potentially profound negative implications of immunosuppressants are well known and are a significant aspect of CTA. The complications include increased incidence of opportunistic infections, increased risk of malignancies, and end-organ toxicity. While there have been significant inroads and improvements in toxicity in the arena of immunosuppression, this aspect remains a significant hurdle to wide spread application of the technology. Research efforts in the area of tolerance induction and minimal immunotherapy regimens would greatly reduce the risk benefit ratio of these transplants.

While successful transplantation of the composite tissue itself is relatively straight forward for the accomplished microsurgeon, there are subtler, complex technical issues surrounding composite allotransplantation. Preparation of the recipient site and donor tissues are critical and require precision. There is the potential for considerable blood loss. Surgical anatomy of the affected areas is often complex. Revascularization of the composite transplant requires microsurgical expertise for vascular anastamoses as well as nerve repairs to restore protective sensibility and motor function.

Psychosocial Issues

The potentially positive psychological impact of these procedures cannot be overstated. While most patients stand to gain enormous psychological benefit from replacing lost facial tissue or extremities, it is important to remember that patients undergoing all types of transplantation are affected by a number of stressors, including difficulty coping with the burden of complying with strict postoperative medical regimes, and understanding complicated issues associated with the many side effects and risks from immunosuppression. Patients may experience swings in emotion including gratitude and guilt in relation to the donor and his/her family, and may take on additional stress with self perceived responsibility for success or failure of transplantation operations.

CTA patients, particularly those undergoing facial transplant, may experience additional psychological issues as the transplant is highly visible. Patients may have difficulties integrating the transplant into existing body image and identity. In facial transplantation the differences in deficits of nonverbal communication and possible lack of improvement in facial animation may be problematic. Patients may experience difficulties dealing with the reactions of friends and family members to a different appearance. They may have fear associated with graft failure that may result in ongoing anxiety and hyper vigilance for signs of rejection, coupled with anxiety that appearance will return to preoperative levels of disfiguration, or worse, if the graft fails.

Research & Clinical Collaboration

CTA offers the possibility of restoring physical and emotional wholeness to a population of individuals who may have very few traditional reconstructive options, but because of these technical, medical and psychological challenges, a complete CTA program necessitates a multi-disciplinary approach to the broader application of the technology. The University of Texas Health Science Center in Houston has a longitudinal experience with solid organ transplantation and an experienced team of experts, including surgeons, nurses, immunologists and ethicists. MD Anderson's Department of Plastic Surgery has faculty with expertise in microsurgical transfer, hand and facial surgery, as well as research experience in CTA. 

The goals of this joint effort include basic science research as well as clinical applications of composite tissue transplantation reconstruction of defects of the face, hand and trunk that will be undertaken with Institutional Review Board (IRB) approval. This collaboration is in progress and is targeted to provide refinement of the basic science and technical aspects of CTA, outcomes assessments of these techniques and as advancements in immunosuppressant therapies progress, pave the way for the application of composite tissue approaches to the management of complex facial and extremity injuries and deformities.

Faculty

UT-Houston Health Science Center

• Richard Andrassy, M.D., F.A.C.S.
• John Holcomb, M.D.