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A Novel Approach to Pattern Dermal Papilla Spheroids in Dermal-Epidermal Composites Using Non-Adherent Microwell
E Cate Wisdom1,2, Donald C Aduba3,4, Owen Lewis1,2
1USU Center for Biotechnology (4DBio3), Department of Radiology and Bioengineering, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Bioengineering (Basel, Switzerland)
|December 30, 2025
Summary
This study uses 3D printing to create patterned dermal papilla spheroids for enhanced skin regeneration. This novel bioengineering approach promotes functional human skin regrowth, improving outcomes after injury.
Area of Science:
- Biomaterials Engineering
- Tissue Engineering
- Regenerative Medicine
Background:
- Bioengineered dermal-epidermal composites (DECs) show potential for skin regeneration and hair follicle neogenesis.
- Human dermal papilla cells (HDPCs) as 3D spheroids enhance hair follicle formation within DECs.
Purpose of the Study:
- To develop a 3D printing strategy for spatially patterning HDPC spheroids in DECs.
- To optimize the design of patterned HDPC spheroids within the extracellular matrix for improved skin regeneration.
Main Methods:
- Utilized 3D printed polydimethylsiloxane (PDMS) microwell arrays to pattern HDPC spheroids.
- Constructed DECs with patterned HDPC spheroids embedded in a collagen matrix and overlaid with keratinocytes.
- Assessed spheroid characteristics, cell viability, gene expression (qPCR), and performed in vivo grafting on immunocompromised mice for 10 weeks.
Main Results:
- Successfully formed patterned, viable HDPC spheroids using microwell arrays and transferred them to the collagen matrix.
- Demonstrated upregulation of key HDPC markers (VCAN, BMP6) in microwell-patterned spheroids compared to monolayers via qPCR.
- Observed successful healing and regeneration in grafted DECs on mice over 10 weeks.
Conclusions:
- 3D printing microwell arrays offer a novel strategy for precisely patterning HDPC spheroids in DECs.
- Optimized spheroid patterning enhances the potential for regenerating functional human skin, rather than scar tissue, post-injury.
Keywords:
3D printingbiofabricationdermal papillagraft survivalhair follicle neogenesisregenerative medicineskin compositewound healing
