1. Identity #
| Field | Value |
|---|---|
| Material | Triple-doped nano-hydroxyapatite (Mg/Si/Zn-HAp) |
| Source study | Design and evaluation of triple-doped nano-hydroxyapatite (Mg/Si/Zn-HAP) as multi-step intelligent scaffold for bone healing |
| Journal | Hybrid Advances 13 (2026), article 100657 |
| DOI | 10.1016/j.hybadv.2026.100657 |
| Accepted | 2 April 2026 |
| Published online | 3 April 2026 |
| Licence | CC BY-NC-ND 4.0 |
| Authors | 26, across 11 faculties and 2 universities |
| Corresponding author | Abdulrazzaq Hammal, University of Aleppo |
| This page’s author | Mulham Fetna (ORCID 0009-0006-4432-798X), co-author, Dept. of Mechatronics Engineering |
| External funding | None |
| Acknowledged | Boundless Academic Services · Sanad Youth for Development · UNFPA Syria |
2. Technical summary #
- A hydroxyapatite in which three dopants are built into the lattice from the first precipitation step — not surface-coated, not post-doped — at 2 mol% Mg, 1 mol% Zn and 2 wt% Si.
- Single-phase hexagonal apatite with ≈17 nm crystallites; the lattice contracts measurably against pure HAp, which is the direct evidence that the dopants entered the structure rather than sitting on it.
- Ion release in simulated body fluid is biphasic — fast over days 1–7, then slow and sustained to day 28.
- Release is pH-responsive: at pH 5.5, cumulative Zn²⁺ at day 7 is +37.5% against pH 7.4, and Ca²⁺ +31.2%. Under alkaline conditions both fall.
- Non-toxic to MG-63 human osteoblasts at the concentrations tested, with a higher IC₅₀ than pure hydroxyapatite.
- Antibacterial, but weaker than gentamicin — the study is explicit about this, and so is this page.
- Fabricated into a porous 3D scaffold at 65 ± 3 % interconnected porosity and 18 ± 2 MPa compressive strength.
3. Composition and synthesis #
Target formula:
$$Ca_{9.70}Mg_{0.20}Zn_{0.10}(SiO_4)_{0.20}(PO_4)_{5.80}(OH)_2$$| Parameter | Value |
|---|---|
| Molar mass | 1003.44 g/mol |
| Magnesium substitution | 2 mol% (at Ca²⁺ sites) |
| Zinc substitution | 1 mol% (at Ca²⁺ sites) |
| Silicon substitution | 2 wt% (SiO₄⁴⁻ at PO₄³⁻ sites) |
| Synthesis basis | 0.09966 mol of the reference formula, for ~100 g product |
| Calcium chloride (CaCl₂, 98%) | 117.8 g |
| Magnesium sulfate (MgSO₄, 99%) | 1.38 g |
| Zinc chloride (ZnCl₂, 98%) | 0.79 g |
| Dipotassium phosphate (K₂HPO₄, 99%) | 96.4 g |
| Sodium silicate (Na₂SiO₃, 28.5% w/w SiO₂) | 3.15 mL |
| Cation solution pH | 5.0 |
| Anion solution pH | 10.5 |
| Precipitation | Dropwise, 60 °C, pH held at 11.2 |
| Post-precipitation | Wash, dry 80 °C, heat treat 600 °C |
| Yield | 98.2 g (98.2 % of target) |
The published abstract prints the formula as
(PO₄)₅.₇₀(OH)₀and the methods section as(PO₄)₅.₈ar. Both are typographical errors; the form above is the one given in the results section and is the one used throughout this site.
4. Structural and morphological characterisation #
| Technique | Result |
|---|---|
| XRD phase | Pure hexagonal hydroxyapatite, space group P6₃/m, ref. JCPDS 09-0432. No secondary phase. |
| Crystallite size | ≈17 nm, from the (211) peak |
| Lattice parameter a | 9.39 Å (pure HAp: 9.42 Å) |
| Lattice parameter c | 6.86 Å (pure HAp: 6.88 Å) |
| FT-IR — O–H (adsorbed water) | 3468, 1636 cm⁻¹ |
| FT-IR — P–O asymmetric stretch ν₃ | 1085, 1022 cm⁻¹ |
| FT-IR — O–P–O bend ν₄ | 602, 567 cm⁻¹ |
| FT-IR — peak character | Broadened and partially merged vs. crystalline pure HAp, indicating reduced crystallographic order from multi-ion doping |
| AFM roughness Sa | 6.8 ± 0.5 nm |
| AFM roughness Sq | 8.9 ± 0.6 nm |
The lattice contraction is the load-bearing evidence here: Mg²⁺ (≈0.72 Å) and Zn²⁺ (≈0.74 Å) replacing Ca²⁺ (≈1.00 Å) compresses the cell, and silicate substituting for phosphate adds further strain. A material that merely had these elements on its surface would not show it.
5. Ion release data #
All charts below are drawn from the study’s own tables. They are original graphics, not reproductions of the paper’s figures.
5.1 Cumulative release in simulated body fluid, 28 days #
Day-28 totals: Ca²⁺ 72.6 ± 2.5 mg/L · Si 10.8 ± 0.7 mg/L · Mg²⁺ 9.2 ± 0.8 mg/L · Zn²⁺ 3.6 ± 0.3 mg/L. Conditions: 100 mg powder in 50 mL SBF (Kokubo & Takadama), 37 °C, 120 rpm orbital shaker, 0.22 µm filtration, ICP-OES quantification, n = 3.
5.2 pH-responsive release at day 7 #
Relative to pH 7.4: Zn²⁺ +37.5% and Ca²⁺ +31.2% at pH 5.5; Zn²⁺ −15.3% and Ca²⁺ −9.5% at pH 8.0. Conditions: 20 mg powder in 10 mL buffer, constant ionic strength (0.15 M NaCl), 37 °C, sampled days 1, 3 and 7, n = 3 per pH.
This is a four-point static comparison, not a time-course of a system returning to a setpoint. The measurement shows release rate varying with ambient pH; it does not show the material detecting and correcting a deviation.
6. Biocompatibility #
Cell line MG-63 (ATCC CRL-1427), human osteoblastic. DMEM + 10 % FBS, 37 °C, 5 % CO₂. Extracts prepared per ISO 10993-12:2021. MTT assay, absorbance 570 nm against 650 nm reference. Three biological replicates, three technical replicates each. Classification per ISO 10993-5: non-toxic ≥ 80 %, slightly toxic 70–79 %, moderately toxic 50–69 %, toxic < 50 %.
6.1 Viability against extract concentration #
6.2 Dose–response, direct suspension #
| Parameter | Mg/Si/Zn-HAp | Pure HAp |
|---|---|---|
| IC₅₀ at 72 h | 3.8 ± 0.2 mg/mL | 2.5 ± 0.3 mg/mL |
| Viability, diluted extracts (≤25 % v/v) | ≥ 95 % at 24, 48 and 72 h | — |
| Viability, direct suspension ≤ 1 mg/mL | ≥ 92 % at all timepoints | — |
| Classification, ≤ 50 % v/v extract | Non-toxic (ISO 10993-5) | Non-toxic |
Chart 6.2 plots the doped material only. The study’s “Pure HAp” comparison is a single 24/48/72 h triplet with no stated concentration, so it cannot honestly be drawn as a dose–response curve; its IC₅₀ is given in the table above instead.
7. Antimicrobial data #
Disc diffusion (6 mm discs, 20 µL of 100 mg/mL suspension) and agar dilution MIC per CLSI, on Mueller-Hinton agar, 37 °C, 24 h, inoculum 0.5 McFarland (~1.5 × 10⁸ CFU/mL), n = 3.
| Parameter | Staphylococcus aureus ATCC 6538 | Escherichia coli ATCC 8739 |
|---|---|---|
| Inhibition zone, Mg/Si/Zn-HAp at 100 mg/mL | 12.5 ± 0.8 mm | 10.2 ± 0.6 mm |
| Inhibition zone, gentamicin 30 µg | 24.3 ± 1.2 mm | 22.7 ± 1.0 mm |
| MIC | 1.5 mg/mL | 2.0 mg/mL |
The material is roughly half as effective as gentamicin by zone diameter. It is not an antibiotic replacement; the relevance is that a structural implant carries some intrinsic resistance to colonisation at the site, where local concentrations are far higher than systemic.
8. 3D scaffold parameters #
| Parameter | Value |
|---|---|
| Fabrication route | Indirect — sacrificial 3D-printed PLA mould |
| Geometry | Hollow half-cylinder, mimicking a bone-marrow canal |
| Outer diameter | 15 mm |
| Inner diameter | 8 mm |
| Length | 30 mm |
| Slurry solids | 60 % Mg/Si/Zn-HAp |
| Binder system | Polyethylene glycol + polyvinyl alcohol, methylcellulose anti-settling agent |
| Stage 1 — drying | 120 °C for 48 h |
| Stage 2 — organic burnout | 600 °C |
| Stage 3 — sintering | 1200 °C for 2 h |
| Bulk density ρ_bulk | 1.09 ± 0.03 g/cm³ |
| True density ρ_true | 3.12 ± 0.05 g/cm³ |
| Porosity (helium pycnometry) | 65 ± 3 % interconnected |
| Compressive strength | 18 ± 2 MPa |
| Stated suitability | Restorative use in non-weight-bearing bone defects |
Burnout and sintering are separate stages at different temperatures. The organics leave at 600 °C; densification happens afterwards at 1200 °C. Collapsing the two is a common misreading — the manufacturing breakdown covers why the distinction matters.
For context, human cancellous bone is around 2–12 MPa in compression (Budharaju et al., 2023).
9. Instrumentation #
| Measurement | Instrument |
|---|---|
| XRD | Bruker D8 Advance, Cu Kα (λ = 1.5406 Å), 40 kV / 40 mA, 2θ 10–60° |
| FT-IR | Thermo Scientific Nicolet iS50, 400–4000 cm⁻¹, KBr pellets |
| AFM | NanoSurf FlexAFM, dynamic contact mode, Tap190Al-G cantilever (190 kHz, 48 N/m) |
| Ion quantification | PerkinElmer Optima 8300 ICP-OES, 1:10 dilution in 2 % HNO₃, R² > 0.999 |
| Absorbance | Molecular Devices SpectraMax iD5 |
| Sonication | Branson Sonifier 250, 40 kHz, 15 min |
| Statistics | GraphPad Prism 10.1.0; one-way ANOVA with Tukey’s test; IC₅₀ by non-linear logistic regression |
10. Limitations #
The study is explicit about what it does not establish. Reproduced here because a data sheet that omits them is not a data sheet.
- Biological evaluation used a single cell line (MG-63) in vitro, with no assessment of osteogenic differentiation or of more complex cellular interactions.
- Ion release was measured in closed systems, which cannot reproduce physiological fluid dynamics in a living body.
- Mechanical evaluation was static compression only — no fatigue or cyclic loading.
- Antimicrobial testing covered two standard laboratory strains, with no clinically relevant or resistant isolates.
- Scaffold properties are partly a function of the indirect printing route itself.
- There is no in vivo work at all: no biodistribution, no systemic toxicity, no bone formation.
The study’s own recommended next steps are in vivo animal models, biomechanical evaluation under cyclic loading, growth-factor loading, and optimisation of the doping ratio.
11. How to cite #
Hammal, A., Al-Hamed Al-Duihib, H., Shawwah, S., Kanawati, A., Boudakah, F., Khayat, M., Masry, A., Hamad, A., Alsadr, M., Ajam, H., Ibesh, H., Kalaji, L., Samara, L., Almohamad, M., Manafikhi, M., Kassir, M., Olabi, S., Salahieh, M. M., Mouselly, E., Markabi, M., Hafez, L. A., Karkar, S., Batal, S., Fetna, M., Sheikh Alkassabeen, B., & Hamad, O. A. (2026). Design and evaluation of triple-doped nano-hydroxyapatite (Mg/Si/Zn-HAP) as multi-step intelligent scaffold for bone healing. Hybrid Advances, 13, 100657. https://doi.org/10.1016/j.hybadv.2026.100657
@article{Hammal2026MgSiZnHAp,
title = {Design and evaluation of triple-doped nano-hydroxyapatite (Mg/Si/Zn-HAP) as multi-step intelligent scaffold for bone healing},
author = {Hammal, Abdulrazzaq and Al-Hamed Al-Duihib, Hiba and Shawwah, Sara and Kanawati, Adeela and Boudakah, Fathia and Khayat, Mohamad and Masry, Adnan and Hamad, Asmaa and Alsadr, Malak and Ajam, Haifaa and Ibesh, Hasan and Kalaji, Lana and Samara, Leen and Almohamad, Majed and Manafikhi, Mohamad and Kassir, Muhammad and Olabi, Sedra and Salahieh, Mohammad Moneer and Mouselly, Eman and Markabi, Mais and Hafez, Leen Almaha and Karkar, Sana and Batal, Sedra and Fetna, Mulham and Sheikh Alkassabeen, Bahia and Hamad, Ola Alaa},
journal = {Hybrid Advances},
volume = {13},
pages = {100657},
year = {2026},
issn = {2773-207X},
doi = {10.1016/j.hybadv.2026.100657}
}TY - JOUR
TI - Design and evaluation of triple-doped nano-hydroxyapatite (Mg/Si/Zn-HAP) as multi-step intelligent scaffold for bone healing
AU - Hammal, Abdulrazzaq
AU - Fetna, Mulham
JO - Hybrid Advances
VL - 13
SP - 100657
PY - 2026
DO - 10.1016/j.hybadv.2026.100657
SN - 2773-207X
ER -