Introduction: Loss or damage of penile tissue due to trauma and disease are life-defining injuries for those affected. Restoration of sexual function is necessary to support recovering psychologically and reestablish the prospect of leading a full and productive life. Recently, the concept of tissue engineering has been proposed to address the goal of restoring normal anatomical tissue configuration and erectile function.
Methods: A penile construct has been engineered by seeding autologous, ex vivo-expanded smooth muscle and endothelial cells seeded onto a naturally derived acellular corporal tissue matrix that possesses the same architecture as native corpora. The proposed clinical indication for the engineered product was for treatment of damaged penile corpora cavernosa. Autologous endothelial cells (EC) and smooth muscle cells (SMC) were isolated from a biopsy obtained from the patient’s cavernosum. Scaffolding was generated by decellularizing a donor penile body. This acellular scaffold was seeded with cells isolated and expanded from the patient’s biopsy. Once seeded, the engineered penile tissue construct was matured in a bioreactor.
Results: A robust process, developed in WFIRM RMCC Process Development, is being translated into GMP Manufacturing for the production of a clinical grade engineered penile tissue construct. In-process and release testing procedures have been established for the utilization of autologous cells and decellularized donor scaffold, to deliver a sterile engineered penile tissue final product. Cells were characterized by studying growth kinetics, identity and purity through immunophenotyping and viability assessments. Decellularized scaffolds are evaluated for acellularity through the absence of DNA and cell nuclei. The final product construct has been characterized for cell viability and distribution on the donor scaffold.
Conclusions: Processes for isolating and expanding the cells, decellularization of a donor penile body and production of a final product construct is currently being been optimized and validated to conform to FDA requirements. An investigational New Drug (IND) application for the project has been approved from the Food and Drug Administration (FDA) for carrying out Phase I safety study for this engineered penile tissue product.
Source of Funding: This work was supported by the Army, Navy, NIH, Air Force, VA and Health Affairs to support the AFIRM II effort, under Award No. W81XWH-13-2-0052. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.