Intraoperative bioprinting of human adipose-derived stem cells and extra-cellular matrix induces hair follicle-like downgrowths and adipose tissue formation during full-thickness craniomaxillofacial skin reconstruction

Youngnam Kang; Miji Yeo; Irem Deniz Derman; Dino J. Ravnic; Yogendra Pratap Singh; Mecit Altan Alioglu; Yang Wu; Jasson Makkar; Ryan R. Driskell; Ibrahim T. Ozbolat

Bioactive Materials (Mar 2024)

Intraoperative bioprinting of human adipose-derived stem cells and extra-cellular matrix induces hair follicle-like downgrowths and adipose tissue formation during full-thickness craniomaxillofacial skin reconstruction

Youngnam Kang,
Miji Yeo,
Irem Deniz Derman,
Dino J. Ravnic,
Yogendra Pratap Singh,
Mecit Altan Alioglu,
Yang Wu,
Jasson Makkar,
Ryan R. Driskell,
Ibrahim T. Ozbolat

Affiliations

Youngnam Kang: Engineering Science and Mechanics Department, Penn State University, University Park, PA, 16802, USA; The Huck Institutes of the Life Sciences, Penn State University, University Park, PA, 16802, USA
Miji Yeo: Engineering Science and Mechanics Department, Penn State University, University Park, PA, 16802, USA; The Huck Institutes of the Life Sciences, Penn State University, University Park, PA, 16802, USA
Irem Deniz Derman: Engineering Science and Mechanics Department, Penn State University, University Park, PA, 16802, USA; The Huck Institutes of the Life Sciences, Penn State University, University Park, PA, 16802, USA
Dino J. Ravnic: The Huck Institutes of the Life Sciences, Penn State University, University Park, PA, 16802, USA; Department of Surgery, College of Medicine, Penn State University, Hershey, PA, 17033, USA
Yogendra Pratap Singh: Engineering Science and Mechanics Department, Penn State University, University Park, PA, 16802, USA; The Huck Institutes of the Life Sciences, Penn State University, University Park, PA, 16802, USA
Mecit Altan Alioglu: Engineering Science and Mechanics Department, Penn State University, University Park, PA, 16802, USA; The Huck Institutes of the Life Sciences, Penn State University, University Park, PA, 16802, USA
Yang Wu: School of Mechanical Engineering and Automation, Harbin Institute of Technology, Shenzhen, 518055, China
Jasson Makkar: School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA, 99164, USA
Ryan R. Driskell: School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA, 99164, USA
Ibrahim T. Ozbolat: Engineering Science and Mechanics Department, Penn State University, University Park, PA, 16802, USA; The Huck Institutes of the Life Sciences, Penn State University, University Park, PA, 16802, USA; Department of Biomedical Engineering, Penn State University, University Park, PA, 16802, USA; Materials Research Institute, Penn State University, University Park, PA, 16802, USA; Department of Neurosurgery, Pennsylvania State College of Medicine, Hershey, PA, 17033, USA; Penn State Cancer Institute, Penn State University, Hershey, PA, 17033, USA; Department of Medical Oncology, Cukurova University, Adana, 01130, Turkey; Corresponding author. Engineering Science and Mechanics Department, Penn State University, University Park, PA, 16802, USA.

Journal volume & issue: Vol. 33
pp. 114 – 128

Abstract

Read online

Craniomaxillofacial (CMF) reconstruction is a challenging clinical dilemma. It often necessitates skin replacement in the form of autologous graft or flap surgery, which differ from one another based on hypodermal/dermal content. Unfortunately, both approaches are plagued by scarring, poor cosmesis, inadequate restoration of native anatomy and hair, alopecia, donor site morbidity, and potential for failure. Therefore, new reconstructive approaches are warranted, and tissue engineered skin represents an exciting alternative. In this study, we demonstrated the reconstruction of CMF full-thickness skin defects using intraoperative bioprinting (IOB), which enabled the repair of defects via direct bioprinting of multiple layers of skin on immunodeficient rats in a surgical setting. Using a newly formulated patient-sourced allogenic bioink consisting of both human adipose-derived extracellular matrix (adECM) and stem cells (ADSCs), skin loss was reconstructed by precise deposition of the hypodermal and dermal components under three different sets of animal studies. adECM, even at a very low concentration such as 2 % or less, has shown to be bioprintable via droplet-based bioprinting and exhibited de novo adipogenic capabilities both in vitro and in vivo. Our findings demonstrate that the combinatorial delivery of adECM and ADSCs facilitated the reconstruction of three full-thickness skin defects, accomplishing near-complete wound closure within two weeks. More importantly, both hypodermal adipogenesis and downgrowth of hair follicle-like structures were achieved in this two-week time frame. Our approach illustrates the translational potential of using human-derived materials and IOB technologies for full-thickness skin loss.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

About the journal

Abstract

Keywords