# Bone Induction as a Function of Size and Chemical Composition of Calcium Phosphate Granules in Osteogrow-C Evaluated in Animal Models: A 1-Year Follow-Up

**Authors:** Nikola Stokovic, Natalia Ivanjko, Marina Milesevic, Katarina Muzina, Marko Pecin, Drazen Maticic, Slobodan Vukicevic

PMC · DOI: 10.34133/bmr.0337 · Biomaterials Research · 2026-02-25

## TL;DR

This study examines how the size and composition of calcium phosphate granules in Osteogrow-C affect bone formation and implant stability in animal models over one year.

## Contribution

The study introduces Osteogrow-C, a novel device combining rhBMP6 with calcium phosphate granules, and evaluates its bone-inductive properties in two animal models.

## Key findings

- Smaller CaP granules promote higher bone volume and density regardless of composition.
- TCP granules are more resorbed compared to HA or biphasic compositions.
- In the rabbit PLF model, TCP and TCP/HA 80/20 ceramics showed the highest resorption rates.

## Abstract

Calcium phosphate (CaP) ceramics are widely used in bone regenerative medicine for their osteoconductive properties. Osteogrow-C is a novel device that comprises recombinant human bone morphogenetic protein 6 (rhBMP6) in autologous blood coagulum, utilizing ceramics as a compression-resistant matrix. This study evaluated how CaP granule size and composition affect bone formation and implant integrity in 2 relevant animal models: the rat subcutaneous model and rabbit posterolateral lumbar fusion (PLF) model, over 1 year. The implants in the rat model had varying granule size ranges (74 to 420 μm, 500 to 1,700 μm, 2,360 to 4,000 μm) and compositions [β-tricalcium phosphate (β-TCP), hydroxyapatite (HA), and biphasic ceramics (TCP/HA 80/20)]. Micro-computed tomography (CT) and histology showed that Osteogrow-C induced bone formation on all ceramic scaffolds, with smaller granules resulting in higher bone volume and density, regardless of composition. TCP granules were most resorbed, but residual ceramics persisted in all groups. Based on these findings, Osteogrow-C, containing small granules with different compositions (TCP, HA, TCP/HA 80/20, and TCP/HA 40/60), was further tested in the clinically relevant rabbit PLF model and induced fusion of transverse processes. Importantly, ceramics were more resorbed in the rabbit PLF model, with TCP and TCP/HA 80/20 ceramics showing the highest resorption rate, while HA remained intact. Osteogrow-C containing HA showed increased bone volume; however, biomechanical strength and thicker cortical bone were achieved with TCP and biphasic calcium phosphate (BCP). Finally, in the rat model, bone volume was primarily dependent on granule size, with smaller granules promoting greater bone formation and density. Conversely, in the PLF model, the composition played a more important role—affecting ceramic resorption, bone volume, and biomechanical properties.

## Linked entities

- **Chemicals:** calcium phosphate (PubChem CID 24456), hydroxyapatite (PubChem CID 14781), HA (PubChem CID 854026)
- **Species:** Mus musculus (taxon 10090), Oryctolagus cuniculus (taxon 9986)

## Full-text entities

- **Genes:** Pdlim3 (PDZ and LIM domain 3) [NCBI Gene 114108] {aka Actn2lp, Alp}, Bmp6 (bone morphogenetic protein 6) [NCBI Gene 25644] {aka VGR}
- **Diseases:** inflammatory (MESH:D007249), degenerative spinal diseases (MESH:D019636), distal radius fracture (MESH:D000092503), PLF (MESH:C563613), bone (MESH:D001847), musculoskeletal diseases (MESH:D009140), TCP (MESH:C564276)
- **Chemicals:** aluminum (MESH:D000535), paraffin (MESH:D010232), ABC (-), gold (MESH:D006046), P (MESH:D010758), phosphate (MESH:D010710), hematoxylin (MESH:D006416), oxygen (MESH:D010100), Nitrogen (MESH:D009584), EDTA (MESH:D004492), xylazine (MESH:D014991), HA (MESH:D017886), acrylic resin (MESH:D000180), picrofuchsin (MESH:C014755), carbon (MESH:D002244), palladium (MESH:D010165), water (MESH:D014867), Ca3(PO4)2 (MESH:C485817), BCP (MESH:C074950), TCP (MESH:C049563), CaP (MESH:C020243), eosin (MESH:D004801), ethyl alcohol (MESH:D000431), formalin (MESH:D005557), Ca (MESH:D002118)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Canis lupus familiaris (dog, subspecies) [taxon 9615], Homo sapiens (human, species) [taxon 9606], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Ovis aries (domestic sheep, species) [taxon 9940]
- **Mutations:** 4C to F

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12932868/full.md

## References

49 references — full list in the complete paper: https://tomesphere.com/paper/PMC12932868/full.md

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Source: https://tomesphere.com/paper/PMC12932868