# Combined Stromal Vascular Fraction and HGF-Functionalized Self-Assembling Peptide Hydrogel Improves Intracerebral Hemorrhage Repair in Rats

## TL;DR

A new treatment combining a cell therapy and a special hydrogel improves brain recovery after bleeding in rats.

## Contribution

A novel combinatorial strategy using SVF and HGF-functionalized hydrogel for ICH repair is introduced.

## Key findings

- Combined therapy reduced hematoma volume, brain swelling, and harmful inflammation in rats.
- The treatment improved motor skills and preserved brain structure over six weeks.
- Myelinated axons were better protected with thicker myelin sheaths in treated rats.

## Abstract

Intracerebral hemorrhage (ICH) remains a devastating condition with no available therapies that can effectively mitigate secondary injury and promote neurological repair. This research presents a novel combinatorial regenerative strategy, concurrently delivering adipose-derived stromal vascular fraction (SVF) within an adhesive self-assembling peptide (HGF-RADA16-IKVAV) nanohydrogel (HGF). In a clinically relevant rat model of ICH with hematoma evacuation, the combined therapy of HGF and SVF demonstrated synergistic and enhanced efficacy. In the short term, the combined therapy demonstrated hemostatic benefits, and significantly reduced hematoma volume, brain edema, neuronal apoptosis and neuroinflammation indicated by pro-inflammatory markers (NLRP3, caspase-1, Iba-1, CD68, GFAP) while increasing the levels of anti-inflammatory (CD206) and angiogenic (CD31) markers. Longitudinal behavioral assessments conducted over six weeks demonstrated persistent and significant improvements in motor coordination, forelimb strength, and gait parameters within the HGF + SVF group, surpassing all monotherapies. Ultrastructural analysis also showed that myelinated axons were better preserved at the injury border, with thicker myelin sheaths. These findings demonstrate that the co-administration of SVF with an adhesive and hemostatic hydrogel collaboratively diminishes secondary injury, modulates neuroinflammation, and promotes functional and structural brain recovery following ICH, indicating a promising and translatable strategy.