Objectives: We herein propose to use a combination of mechanically isolated adipose-derived progenitor cells with various scaffolds plus functionalization to engineer dermal tissue.
Introduction: The restoration of dermis after injury remains a challenge in today’s medicine. Beyond complex flap reconstruction, the field of regenerative medicine and tissue engineering is eager to identify less invasive pathways to resolve this issue, foremost by protecting the dermis, e.g. by enzymatic debridement, and creating a well-vascularized dermal layer. Autologous cell transplantation only has shown mixed results and many clinicians and researchers see scaffolds as a necessary carrier to unleash the full regenerative capacity of cells. Also, functionalization of constructs may further boost tiss
Materials / method: Human SVF cells isolated by enzymes or mechanical protocols were cultured on alginate and gelatine-based hydrogels and commercially available dermal substitutes for up to 14 days under standard cell culture conditions. The constructs were characterized histologically for cellular ingrowth and vessel-like formation and protein expression. Protein expression in the supernatant was analyzed for total protein concentration and specific growth factors. Finally, functionalization was performed by adding a recombinant regenerative protein named macrophage migration inhibitory factor (MIF)-2.
Results: Both alginate and gelatine-based hydrogels permitted long term survival of SVF cells in vitro. When cultured with commercially available dermal substitutes, mechanically isolated SVF cells showed limited penetration with no visible vessel-like structure formation. Total protein concentration and VEGF release was high in biologic dermal substitutes. Finally, long-term release of MIF-2 protein required on-top encapsulation in synthetic particles.
Conclusion: The cultivation of SVF cells in hydrogels shows promising results. In stiff commercial dermal substitutes, by contrast, advanced strategies to increase the ingrowth of cells may be necessary. Also, functionalization by recombinant proteins is possible but demands finely-tuned, protein-specific release carriers.
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这项工作的完成感谢以下机构的支持: German Research Foundation (DFG), Novartis Foundation for Medical-Biological Research