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Mg/Si/Zn-HAp Technical Data Sheet: Triple-Doped Nano-Hydroxyapatite

Mulham Fetna
Author
Mulham Fetna
Renaissance Engineer
Table of Contents
A reference sheet, not an article. Every parameter, measurement and condition from the published study in one place — tabulated, charted from the source data, and citable. If you want the story, read the announcement; if you want the mechanism, read the closed-loop breakdown.

1. Identity
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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
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  • 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
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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)₀ and 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
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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
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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
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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
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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
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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
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6.2 Dose–response, direct suspension
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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
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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
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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
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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
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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
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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  -

12. Frequently asked
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What is triple-doped hydroxyapatite?
Hydroxyapatite is the mineral that makes up the hard part of bone, and it can be made synthetically. Triple-doped hydroxyapatite has three different elements substituted into its crystal structure instead of one. In this material those are magnesium (2 mol%), zinc (1 mol%) and silicon (2 wt%), added during the initial chemical synthesis rather than coated on afterwards, so they sit inside the lattice.
What is the compressive strength of a Mg/Si/Zn-HAp scaffold?
18 ± 2 MPa, measured in uniaxial compression on a scaffold with 65 ± 3 % interconnected porosity. For comparison, human cancellous bone is roughly 2–12 MPa. The study limits its claim to non-weight-bearing bone defects, and the testing was static — no fatigue or cyclic loading was performed.
Is zinc-doped hydroxyapatite toxic to cells?
Not at the concentrations tested here. On MG-63 human osteoblast cells, diluted extracts (≤25 % v/v) kept viability at or above 95 % over 72 hours, and direct suspensions up to 1 mg/mL stayed above 92 % — non-toxic under ISO 10993-5, which sets the threshold at 80 %. The IC₅₀ was 3.8 ± 0.2 mg/mL against 2.5 ± 0.3 mg/mL for undoped hydroxyapatite. Zinc becomes a problem at higher loadings; this material uses 1 mol%.
What is pH-responsive ion release?
It means the material dissolves at different rates depending on how acidic its surroundings are. Injured and infected tissue turns acidic. At pH 5.5, this material released +37.5% more zinc over seven days than at normal body pH of 7.4, and under alkaline conditions it released −15.3% less. Since zinc is the antibacterial component, more of it comes out when infection risk is highest. Note this was measured as a four-point comparison across fixed pH values, not as a system tracking a changing environment over time.
How was the 3D bone scaffold made?
By indirect printing. A negative mould was 3D-printed in PLA in the shape of a bone-marrow canal (15 mm outer diameter, 8 mm inner, 30 mm long), filled with a 60 % ceramic slurry, dried at 120 °C, then fired in two further stages — organics burned out at 600 °C, then sintered at 1200 °C for 2 hours. The ceramic itself was never printed directly.
Is this material ready for use in patients?
No. All work reported is in vitro. There is no animal study, no biodistribution or systemic toxicity data, no osteogenic differentiation assay, and no fatigue testing. It is a characterised material with a fabricated prototype scaffold — the stage before preclinical work begins, not after it.
Mulham Fetna
Author
Mulham Fetna
Renaissance Engineer

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