Aug 01, 2024 The biofabrication of skin components presents an exciting opportunity to heal burn wounds, create hair follicle transplants for individuals with alopecia, and test new drugs and cosmetics. While tissue engineering that achieves the full skin complexity remains a challenge, four research and industry panelists talked to us about the advances they are making in skin component 3D bioprinting at our 3DHEALS event.
Incorporating vascular networks in 3D-printed skin
Dr. Pankaj Karande, Associate Professor of Chemical and Biological Engineering at Rensselaer Polytechnic Institute, is motivated to close the gap between the simplistic structure of current skin substitutes and the actual complex biology of human skin. Components in addition to the skin layers, such as vasculature, hair follicles, sweat glands, and more, need to be considered.
Dr. Karande saw disadvantages with patterning vasculature in artificial skin, as it did not create vessel networks representative of those in humans. Instead, Dr. Karande and colleagues focused on vessel self-assembly by changing the cell types and microenvironments surrounding the bioprinted endothelial cells, such as adding fibroblasts from different sources to influence the endothelial vessels’ branching length and lumen diameter. They show that incorporating their vasculature in printed skin enables more robust adherence to the wound site of mice since the new vessels can connect to the host vessels, compared to grafts without vasculature, which would come off due to poor integration with the host.
Bioprinting hair follicles: hope for improved restoration following hair loss
Dr. Meghan Samberg, Chief Development Officer at Stemson Therapeutics, uses induced pluripotent stem cells (iPSCs) to create follicular units for transplantation. The preclinical-stage company is focusing on developing a treatment for individuals with hair loss, such as alopecia areata, scarring alopecia, and chemotherapy-induced hair loss.
Based on their solution theoretically, peripheral blood mononuclear cells are isolated from patient blood samples and reprogrammed into iPSCs. The cells are then differentiated into dermal papilla and epithelial stem cells, combined to form hair follicle units, and transplanted into patients. Dr. Samberg described how they have achieved dermal papilla cells that produce expected characteristic biomarkers and work towards epithelial cells closer to their reference cells.
The company found that a key consideration in transplanting their hair follicles was the need for a mechanism to guide the hair growth’s directionality. Otherwise, the hair would grow sideways along the dermis instead of emerging out. In their earlier attempts, they used two-photon polymerization (2PP) printing to create micron-scale scaffolds for the cells. Their hair follicle organoids were placed in a cage-like scaffold implanted into the tissue, and an attached rod structure extending out of the scalp induced keratinocytes at the skin’s surface to re-epithelize downward, encouraging proper pore orientation.
However, this approach and their later iterations may not have resulted in high enough cell viability or led to the cells migrating out of the scaffold. They have been developing a hydrogel-based bioprinting method that better guides hair directionality and have demonstrated successful results using human skin xenografts in mice.
Manufacturing and scaling up skin bioprinting for research and the clinic
A core aspect of skin bioprinting is the manufacturing process. Dr. Fabien Guillemot, CEO and Founder of Poietis, has created an advanced tissue engineering 3D printer for research and clinical applications called the Next Generation Bioprinting platform. The printer features a laser-assisted bioprinting head that focuses laser pulses on a cell bioink film to eject the ink’s microdroplets onto a substrate and a robotic arm for automation.
The company used laser-assisted bioprinting to create Poieskin, a 3D-printed autologous dermo-epidermal skin substitute, following good manufacturing practices (GMPs) set by the EU. Thanks to automation, the company has reduced the number of manual operations from >100 to only 10 since 2019.
They have also developed quality control methods, including a histological scoring system for assessing fibroblast morphology, layer thickness, and other factors. Now, their sights are set on clinical trials, and they have installed their bioprinting system at the cell therapy facility of a hospital in France to test their protocols. Such point-of-care 3D printing will enable skin bioprinting conveniently within the hospital to reduce manufacturing logistics.
Bioprinting during surgery: fabricating bone and skin on the operating table
With the vision that bioprinting will one day be done intra-operatively, Dr. Ibrahim Tarik Ozbolat, Dorothy Foehr Huck, and J. Lloyd Huck Chair in 3D Bioprinting and Regenerative Medicine and Professor of Engineering Science and Mechanics, Biomedical Engineering, and Neurosurgery at Penn State, described his and colleagues’ work on creating bone and skin composites for craniomaxillofacial procedures.
Using bone ink to differentiate rat stem cells into osteogenic cells, they perform extrusion-based bioprinting directly on the rat skull to fill hole defects. Then, they can use more precise droplet-based bioprinting to deposit their ink, which is made of collagen and fibrinogen to create skin. Rat dermal fibroblasts added to the ink for the dermal layer of skin and keratinocyte growth factor for the epidermal layer resulted in mechanical properties closest to native skin compared to other treatments tested.
In addition to achieving the dermal and epidermal layers of skin, Dr. Ozbolat also described work on bioprinting the hypodermis. From liposuction surgery discards, they obtained adipose-derived stem cells and adipose-derived extracellular matrix to form a hypodermis bioink that is then covered with their dermis bioink. Interestingly, they saw early-stage hair follicle formation by day 14 in the rats, showing that printing with adipose-derived extracellular matrix can help with follicle growth.
A bright future for skin bioprinting
While it will take time for new advances to be tested for safety and efficacy, skin bioprinting holds immense potential, with encouraging products such as Stemson’s hair follicle implants and Poietis’ skin, as well as the growing body of research from Dr. Karande and Dr. Ozbolat’s works in incorporating new skin components. To stay updated with the latest in 3D bioprinting space, subscribe to join our future events live.
About the Author:
Peter Hsu
Peter Hsu is an editorial intern for 3DHEALS. He is currently an undergraduate at the University of Illinois Urbana-Champaign and studies bioengineering with a focus on cell and tissue engineering. He is also minoring in computer science with interests in artificial intelligence and image processing. Peter conducts research on using computer vision methods to analyze human tissue images and improving the robustness of machine learning workflows. He is interested in the use of AI to assist tissue engineering and bioprinting research for medical applications. He is passionate about science communication and leads STEM outreach lessons at schools in the central Illinois area.
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