# An Injectable, Osteoconductive Gelatin-Enabled GelMA/HAp Hydrogel Scaffold for Minimally Invasive Bone Tissue Engineering

**Authors:** Juhan Li, Nan Xiang, Lingbin Che, Jianfeng Wu, Dianwen Song

PMC · DOI: 10.3390/bioengineering13020139 · Bioengineering · 2026-01-26

## TL;DR

A new injectable hydrogel scaffold is developed for bone tissue engineering that balances injectability, stability, and cell support for bone regeneration.

## Contribution

A GelMA/HAp hydrogel scaffold is engineered with unmodified gelatin to enhance injectability and bioactivity without compromising mechanical integrity.

## Key findings

- The scaffold prevents HAp sedimentation and allows precise extrusion at physiological temperatures.
- UV crosslinking produces a mechanically robust scaffold with enhanced compressive modulus.
- The scaffold supports high cell viability and promotes osteogenic differentiation of BMSCs.

## Abstract

Despite extensive exploration of gelatin methacryloyl (GelMA)-based hydrogels for bone tissue engineering, their clinical translation is hindered by a critical trade-off: poor precursor stability leads to rapid sedimentation of bioactive fillers like hydroxyapatite (HAp), while formulations optimized for injectability often sacrifice mechanical integrity or handling precision. To overcome this challenge, we report a rheologically engineered, injectable composite hydrogel scaffold that integrates unmodified gelatin as a thermoresponsive viscosity modulator into a GelMA/HAp matrix. The incorporation of gelatin yields a stable, paste-like precursor at physiological temperature, which effectively prevents HAp sedimentation and enables precise, filamentous extrusion. Subsequent UV crosslinking locks the homogeneous structure in place, resulting in a mechanically robust scaffold with significantly enhanced compressive modulus. In vitro studies demonstrate that this biomimetic microenvironment not only supports high viability and proliferation of bone marrow stromal cells (BMSCs) but also potently enhances their osteogenic differentiation, as evidenced by upregulated alkaline phosphatase activity, Runx2 expression, and matrix mineralization. This simple, one-step strategy successfully reconciles injectability, structural fidelity, and bioactivity, offering a highly promising and clinically translatable platform for minimally invasive bone regeneration.

## Linked entities

- **Genes:** RUNX2 (RUNX family transcription factor 2) [NCBI Gene 860]
- **Chemicals:** hydroxyapatite (PubChem CID 14781), HAp (PubChem CID 21876)

## Full-text entities

- **Genes:** SP7 (Sp7 transcription factor) [NCBI Gene 121340] {aka OI11, OI12, OSX, osterix}, BAG1 (BAG cochaperone 1) [NCBI Gene 573] {aka BAG-1, HAP, RAP46}, RUNX2 (RUNX family transcription factor 2) [NCBI Gene 860] {aka AML3, CBF-alpha-1, CBFA1, CCD, CCD1, CLCD}, ALPP (alkaline phosphatase, placental) [NCBI Gene 250] {aka ALP, PALP, PLAP, PLAP-1}, LAP (Laryngeal adductor paralysis) [NCBI Gene 7939], GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, RIEG2 (Rieger syndrome 2) [NCBI Gene 6012] {aka ARS, RGS2}, BGLAP (bone gamma-carboxyglutamate protein) [NCBI Gene 632] {aka BGP, OC, OCN}
- **Diseases:** inflammatory (MESH:D007249), injury to (MESH:D014947), cytotoxicity (MESH:D064420), Irregular bone defects (MESH:D001847)
- **Chemicals:** TRIzol (MESH:C411644), water (MESH:D014867), PMMA (MESH:D019904), calcium phosphate (MESH:C020243), diammonium hydrogen phosphate (MESH:C024788), P (MESH:D010758), phalloidin (MESH:D010590), trisodium citrate (MESH:C514290), polymer (MESH:D011108), FITC (MESH:D016650), EDTA (MESH:D004492), ammonium hydroxide (MESH:D064753), CO2 (MESH:D002245), DAPI (MESH:C007293), Ca (MESH:D002118), Alizarin Red S (MESH:C004468), hydrogen (MESH:D006859), Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (MESH:C546776), Sodium citrate (MESH:D000077559), RGD (MESH:C047981), Glycerol (MESH:D005990), genipin (MESH:C007834), CCK-8 (-), Calcium nitrate (MESH:C059948), HAp (MESH:D017886), arginine (MESH:D001120), aspartic acid (MESH:D001224)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116]
- **Mutations:** C2015S, P0321S, K0510A

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12938435/full.md

## References

32 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938435/full.md

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Source: https://tomesphere.com/paper/PMC12938435