# AI and big data driven knowledge mapping of exosome–hydrogel research in orthopedic regeneration and tissue engineering

**Authors:** Qinghan Li, Liming Lou, Shuaishuai Wang, Minglei Zhang

PMC · DOI: 10.3389/fcell.2026.1786225 · Frontiers in Cell and Developmental Biology · 2026-02-17

## TL;DR

This paper uses AI and big data to map the research and patent landscape of exosome-hydrogel applications in orthopedic regeneration and tissue engineering from 2016 to 2025.

## Contribution

A novel dual-source analysis framework connects academic research and patents to identify translational gaps and innovation opportunities in exosome-hydrogel studies.

## Key findings

- Mesenchymal stem cell-derived exosomes and GelMA or collagen-based hydrogels are central to current research.
- Academic focus is on osteogenesis, while patents lag behind and show temperature-dependent research applications.
- Unpatented propositions like 'hydrogel-encapsulated exosomes' highlight potential for innovation.

## Abstract

Exosome-hydrogel complexes have great potential in regenerative medicine, being able to combine biological signals with structural support. But overall, the knowledge structure and translational connections between academic discoveries and patent deployment are not clear.

A dual-source analysis framework was established to analyze academic papers and patents, illustrating the landscape of exosome–hydrogel research from 2016 to 2025. An interdisciplinary knowledge graph was constructed using topic modeling, entity–relation extraction, and evidence-ranking methods to quantify temporal trends, thematic differences, and translational gaps.

The core components include mesenchymal stem cell–derived exosomes and hydrogels based on gelatin methacrylate (GelMA) or collagen, which form a well-established research foundation. Academic research focuses on osteogenesis, and recent progress mentions angiogenesis and immune regulation. The research application has strong temperature dependence, and patent activities lag behind academic publications. Several high-evidence yet unpatented propositions, such as “hydrogel-encapsulated exosomes” and “exosome-enhanced angiogenesis,” represent potential innovation opportunities.

This study employs a data-driven framework to connect scientific research with transformation. The integration of semantic models and cross - source evidence reflects the evaluation logic of exosome - hydrogel research, and provides support for future research in the field of regenerative biomaterials and the priority of patent strategies.

## Linked entities

- **Chemicals:** gelatin methacrylate (PubChem CID 162641003)

## Full-text entities

- **Genes:** BGLAP (bone gamma-carboxyglutamate protein) [NCBI Gene 632] {aka BGP, OC, OCN}, MRC1 (mannose receptor C-type 1) [NCBI Gene 4360] {aka CD206, CLEC13D, CLEC13DL, MMR, MRC1L1, bA541I19.1}, RUNX2 (RUNX family transcription factor 2) [NCBI Gene 860] {aka AML3, CBF-alpha-1, CBFA1, CCD, CCD1, CLCD}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, MAG (myelin associated glycoprotein) [NCBI Gene 4099] {aka GMA, S-MAG, SIGLEC-4A, SIGLEC4, SIGLEC4A, SPG75}, ATHS (atherosclerosis susceptibility (lipoprotein associated)) [NCBI Gene 470] {aka ALP}, PECAM1 (platelet and endothelial cell adhesion molecule 1) [NCBI Gene 5175] {aka CD31, CD31/EndoCAM, GPIIA', PECA1, PECAM-1, endoCAM}
- **Diseases:** bone defect (MESH:D001847), MSC (MESH:D000092423), inflammation (MESH:D007249), osteogenesis (MESH:D010013)
- **Chemicals:** lipids (MESH:D008055), GelMA (-), HA (MESH:D006820), alginate (MESH:D000464), Chitosan (MESH:D048271), polyethylene glycol (MESH:D011092)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12953459/full.md

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12953459/full.md

## References

34 references — full list in the complete paper: https://tomesphere.com/paper/PMC12953459/full.md

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Source: https://tomesphere.com/paper/PMC12953459