Journal
ANNALS OF SURGERY
Volume 256, Issue 2, Pages 363-370Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/SLA.0b013e31825a02ab
Keywords
regenerative medicine; tissue engineering; solid organ transplantation; extracellular matrix; scaffold; porcine model; decellularization; biocompatibility; recellularization
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Funding
- TATRC
- Marie Curie International Outgoing Fellowship [POIF-GA-2008-221850]
- European Commission under the 7th Framework Program for Research and Development
- Great Ormond Street Hospital Childrens Charity [V1230] Funding Source: researchfish
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Background: It is important to identify new sources of transplantable organs because of the critical shortage of donor organs. Tissue engineering holds the potential to address this issue through the implementation of decellularization-recellularization technology. Objective: To produce and examine acellular renal extracellular matrix (ECM) scaffolds as a platform for kidney bioengineering. Methods: Porcine kidneys were decellularized with distilled water and sodium dodecyl sulfate-based solution. After rinsing with buffer solution to remove the sodium dodecyl sulfate, the so-obtained renal ECM scaffolds were processed for vascular imaging, histology, and cell seeding to investigate the vascular patency, degree of decellularization, and scaffold biocompatibility in vitro. Four whole renal scaffolds were implanted in pigs to assess whether these constructs would sustain normal blood pressure and to determine their biocompatibility in vivo. Pigs were sacrificed after 2 weeks and the explanted scaffolds were processed for histology. Results: Renal ECM scaffolds were successfully produced from porcine kidneys. Scaffolds retained their essential ECM architecture and an intact vascular tree and allowed cell growth. On implantation, unseeded scaffolds were easily reperfused, sustained blood pressure, and were tolerated throughout the study period. No blood extravasation occurred. Pathology of explanted scaffolds showed maintenance of renal ultrastructure. Presence of inflammatory cells in the pericapsular region and complete thrombosis of the vascular tree were evident. Conclusions: Our investigations show that pig kidneys can be successfully decellularized to produce renal ECM scaffolds. These scaffolds maintain their basic components, are biocompatible, and show intact, though thrombosed, vasculature.
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