# Recombinant Amelogenin as a Potential Alternative to Enamel Matrix Derivatives in Periodontal Regeneration: A Scoping Review of Its Biological Activity, Synthesis and Delivery Systems

**Authors:** Jie Dan Denny Luo, Jennifer Mardini, Raymond Lee, Fariba Dehghani, Aaron Schindeler

PMC · DOI: 10.1002/cre2.70325 · 2026-03-06

## TL;DR

This review explores recombinant amelogenin as a potential alternative to enamel matrix derivatives for periodontal regeneration, focusing on its biological activity and delivery methods.

## Contribution

The paper provides a scoping review of recombinant amelogenin's regenerative potential, highlighting its synthesis and delivery systems for periodontal applications.

## Key findings

- Recombinant amelogenin shows consistent preclinical biological activity for periodontal regeneration.
- Most studies used direct dissolution in culture media, with fewer using hydrogels or scaffolds for delivery.
- Evidence remains preclinical and heterogeneous, requiring standardized models and comparisons with existing therapies.

## Abstract

The objective of this review is to evaluate the existing literature on the regenerative potential of recombinant amelogenin, with a particular emphasis on the biological activity, synthesis, and delivery systems relevant to periodontal regeneration.

A comprehensive literature search was conducted across PubMed, Ovid MEDLINE, Scopus and Web of Science to identify studies on recombinant amelogenin for periodontal regeneration. Inclusion criteria encompassed in vitro and animal model studies reporting on cellular growth, regeneration markers, tissue repair and clinical improvements. Data extraction focused on study design, protein source, delivery system, experimental model, and reported biological outcomes. The review was conducted in accordance with the PRISMA‐ScR guidelines and supplemented by a narrative synthesis of the preclinical literature.

The literature search included 23 studies comprising predominantly preclinical cell culture and in vivo mouse studies. Recombinant amelogenin was evaluated across diverse experimental systems and delivery methods, most frequently by direct dissolution in culture media, with fewer studies using injectable hydrogels or scaffold‑based carriers. Although most investigations reported biological activity attributable to recombinant amelogenin, the outcome measures, experimental models, and formulation strategies varied substantially, limiting direct comparison across studies.

Recombinant amelogenin shows consistent preclinical activity supporting its biological plausibility as a regenerative agent. However, evidence remains largely preclinical and heterogeneous. Future studies should employ standardised models, optimised delivery systems, and direct comparisons with established therapies to clarify its translational potential in periodontal regeneration.

## Linked entities

- **Proteins:** AMELX (amelogenin, X-linked)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, IBSP (integrin binding sialoprotein) [NCBI Gene 3381] {aka BNSP, BSP, BSP II, BSP-II, SP-II}, ATHS (atherosclerosis susceptibility (lipoprotein associated)) [NCBI Gene 470] {aka ALP}, PPARD (peroxisome proliferator activated receptor delta) [NCBI Gene 5467] {aka FAAR, NR1C2, NUC1, NUCI, NUCII, PPARB}, RUNX2 (RUNX family transcription factor 2) [NCBI Gene 860] {aka AML3, CBF-alpha-1, CBFA1, CCD, CCD1, CLCD}, CCN2 (cellular communication network factor 2) [NCBI Gene 1490] {aka CTGF, HCS24, IBP-8, IGFBP8, KMD, NOV2}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, BMP2 (bone morphogenetic protein 2) [NCBI Gene 650] {aka BDA2, BMP2A, SSFSC, SSFSC1}, VCAM1 (vascular cell adhesion molecule 1) [NCBI Gene 7412] {aka CD106, INCAM-100}, CREB1 (cAMP responsive element binding protein 1) [NCBI Gene 1385] {aka CREB, CREB-1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, ANGPTL4 (angiopoietin like 4) [NCBI Gene 51129] {aka ARP4, FIAF, HARP, HFARP, NL2, PGAR}, HSPA5 (heat shock protein family A (Hsp70) member 5) [NCBI Gene 3309] {aka BIP, GRP78, HEL-S-89n}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, AREG (amphiregulin) [NCBI Gene 374] {aka AR, AREGB, CRDGF, SDGF}, BGLAP (bone gamma-carboxyglutamate protein) [NCBI Gene 632] {aka BGP, OC, OCN}, MCAM (melanoma cell adhesion molecule) [NCBI Gene 4162] {aka CD146, HEMCAM, METCAM, MUC18, MelCAM}, BMP1 (bone morphogenetic protein 1) [NCBI Gene 649] {aka OI13, PCOLC, PCP, TLD}
- **Diseases:** carcinoma (MESH:D009369), periodontitis"[MeSH (MESH:D006258), tooth loss (MESH:D016388), inflammatory (MESH:D007249), Periodontitis (MESH:D010518), periodontal bone defects (MESH:D016301), bone defect (MESH:D001847), EMD (MESH:D020389)
- **Chemicals:** mHA (MESH:C069357), SDS (MESH:D012967), HAMA (-), Poloxamer 407 (MESH:D020442), CS (MESH:D002586), PGA (MESH:C038550)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Canis lupus familiaris (dog, subspecies) [taxon 9615], Escherichia coli (E. coli, species) [taxon 562], Sus scrofa (pig, species) [taxon 9823], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** Sf9 — Spodoptera frugiperda (Fall armyworm), Spontaneously immortalized cell line (CVCL_0549)

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12964491/full.md

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Source: https://tomesphere.com/paper/PMC12964491