Biology subjects

Baurceanu, I.

Publications and source records attributed to Baurceanu, I..

2 recordsLinked to original sources

bioRxiv2025

Inflammatory Agonists Modulate the Host Response to Type 2 ECM scaffold Immune Environment and Long-Term Remodeling After Severe Traumatic Injury

The immune system is a vital regulator of tissue repair after trauma and the response to implantable scaffolds for regenerative medicine. Decellularized extracellular matrix (ECM) scaffolds promote tissue integration and remodeling following traumatic injury in part due initiating a pro-reparative Type-2 immune response. However, exogenous soluble inflammatory immune signals can be introduced during scaffold implantation, including microbial products in contaminated surgical fields or during immunotherapy to treat autoimmunity and cancer. It remains largely unknown how such immune mediators modulate the ECM scaffold immune environment and subsequent scaffold remodeling. In the present study, we co-delivered 3 distinct inflammatory immune adjuvants (cyclic di-AMP [CDA], monophosphoryl lipid A [MPLA], and granulocyte colony stimulating factor [GM-CSF]) with small intestinal submucosa (SIS) ECM in a murine volumetric muscle loss injury model, evaluating acute (1 week) and long-term (8-week) immune environments and scaffold remodeling. High parameter spectral cytometry, histologic analysis, and PCR revealed differential potentiation of the ECM scaffold microenvironment. Type 2 immune programs including IL-4, eosinophils, CD4 T cells, and CD206/CD86 macrophage ratios were induced in all ECM groups but attenuated by varying amounts with the CDA and MPLA co-delivery. By 8-weeks, inflammation had largely subsided, and histologically ECM with GM-CSF or MPLA showed the greatest degradation and remodeling into adipose tissue. These findings suggest that early pro-inflammatory compound delivery does not abrogate the ECM immune environment but does attenuate some programs while inducing others. These have long-term effects on scaffold remodeling and should be a consideration for surgical reconstruction in patients receiving immune stimulatory therapies.

immunology↗

bioRxiv2023

Extracellular matrix scaffold-assisted tumor vaccines induce tumor regression and long-term immune memory

Injectable scaffold delivery is an immune engineering strategy to enhance the efficacy and reliability of cancer vaccine immunotherapy. The composition and structure of the biomaterial scaffold determines both vaccine release kinetics and inherent immune stimulation via the scaffold host response. Extracellular matrix (ECM) scaffolds prepared from decellularized tissues initiate an acute alternative inflammatory response following implantation, which facilitates wound healing following tumor resection and promotes local cancer immune surveillance. However, it remains unknown whether this environment is compatible with generating protective anti-tumor cytotoxic immunity with local immunotherapy delivery. Here, we engineered an ECM scaffold-assisted therapeutic cancer vaccine that maintained an immune microenvironment consistent with tissue reconstruction. Immune adjuvants MPLA, GM-CSF, and CDA were screened in a cancer vaccine formulated for decellularized small intestinal submucosa (SIS) ECM scaffold co-delivery. Though MPLA and GM-CSF showed the greatest increase in local myeloid cell infiltration, we found that the STING pathway adjuvant CDA was the most potent inducer of cytotoxic immunity with SIS-ECM scaffold delivery. Further, CDA did not diminish hallmark ECM immune responses needed in wound healing such as high Il4 cytokine expression. SIS scaffold delivery enhanced therapeutic vaccine efficacy using CDA and the antigen ovalbumin, curing greater than 50% of established EG.7 tumors in young mice and 75% in 24-week-old mature mice, compared to soluble components alone (0% cured). SIS-ECM scaffold assisted vaccination extended antigen exposure, was dependent on CD8+ cytotoxic T cells, and generated long term anti-tumor memory at least 7 months post-vaccination in both young and mature-aged mice. This study shows that an ECM scaffold is a promising delivery vehicle to enhance cancer vaccine efficacy while being orthogonal to characteristics of pro-healing immune hallmarks.

bioengineering↗