Modeling human hypertrophic scars with 3D preformed cellular aggregates bioprinting

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Tissue Engineering

Background:

• Therapeutic interventions for human hypertrophic scars (HHS) are hindered by the lack of accurate models.
• Existing HHS models fail to replicate native scar architecture and pathological microenvironments.

Purpose of the Study:

• To develop a 3D functional human hypertrophic scar (HHS) model using preformed cellular aggregates (PCA) bioprinting.
• To create a bioink from decellularized extracellular matrix (ECM) and alginate-gelatin (Alg-Gel) hydrogel to mimic scar microenvironmental factors.
• To validate the model's ability to recapitulate early-stage HHS characteristics and assess therapeutic interventions.

Main Methods:

• Developed a bioink using decellularized ECM and Alg-Gel hydrogel.
• Pre-cultured patient-derived fibroblasts in the bioink to form topographic cellular aggregates (PCA).
• Utilized PCA bioprinting to create the 3D functional HHS model.
• Analyzed gene and protein expression, signaling pathways, and in vivo tissue dynamics.
• Evaluated the model's response to anti-scarring drugs.

Main Results:

• The bioprinted model demonstrated well-defined aligned cell structures and self-organized into functional scar tissue.
• The HHS models exhibited characteristics of early-stage HHS, including activated inflammation and cell proliferation pathways.
• The model successfully recapitulated in vivo tissue dynamics of scar formation.
• The in vitro and in vivo models accurately reflected the effects of anti-scarring drug treatments.

Conclusions:

• The novel 3D bioprinted HHS model effectively mimics native scar tissue and microenvironments.
• This model serves as a valuable platform for studying HHS mechanisms and evaluating therapeutic targets.
• The developed model shows potential for rapid drug testing and developing personalized scar treatment strategies.