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. 2021 Sep 29;11(10):2569. doi: 10.3390/nano11102569

Table 3.

Application of nHA for delivery of proteins.

Author (Year) Interventions Dosage Delivery
Approach		 Significant Findings
Curtin et al. (2015) [20]
  • (1)

    Untreated (blank control)

  • (2)

    Gene-free scaffold

  • (3)

    PEI-pVEGF/PEI-pBMP-2 (PEI dual scaffold)

  • (4)

    nHA/pVEGF/nHA-pBMP-2 (nHA dual scaffold)

  • (5)

    PEI-pVEGF and nHA/pBMP-2 (mix dual scaffold)

 * not specified in article Implantable scaffold nHA and combined PEI + nHA scaffolds containing both pBMP-2 and pVEGF showed higher new bone and vessels formation compared to the untreated defect
Itoh et al. (2005) [33]
  • (1)

    Untreated (blank control)

  • (2)

    HAp/Col

  • (3)

    HAp/Col + rhBMP-2 composite
  • (1)

    HAp/Col: HAp/Col only

  • (2)

    HAp/Col + rhBMP-2: HAp/Col + 400 μg/mL rhBMP-2 solution

 Implantable bone graft Complete bone union was observed in both rhBMP-2 and non-rhBMP group, while the group with untreated defect does not show bone bridging throughout the study
Kim et al. (2008) [23]
  • (1)

    Fibrin gel only (blank control)

  • (2)

    Fibrin gel + PLGA/HA

  • (3)

    Fibrin gel + BMP-2

  • (4)

    Fibrin gel + PLGA/HA + BMP-2
  • (1)

    Fibrin gel + PLGA/HA: 0.1 mL Fibrin gel + 10 mg PLGA/HA

  • (2)

    Fibrin gel + BMP-2: 0.1 mL Fibrin gel + 1 μg BMP-2

  • (3)

    Fibrin gel + PLGA/HA + BMP-2: 0.1 mL Fibrin gel + 10 mg PLGA/HA + 1 μg BMP-2

 Implantable gel An improved bone formation was observed in rats implanted with fibrin gels containing BMP-2 and PLGA/HA compared to the rats implanted with fibrin gel alone
Zhang et al. (2016) [30]
  • (1)

    Untreated (blank control)

  • (2)

    nHAC/PLLA

  • (3)

    nHAC/PLLA/P17-BMP-2 (2 mg/g)

  • (4)

    nHAC/PLLA/P17-BMP-2 (10 mg/g)
  • (1)

    nHAC/PLLA/P17-BMP-2: nHAC/PLLA + 2 mg/g or 10 mg/g of P17-BMP-2

 Implantable scaffold Rabbits implanted with scaffold with or without P17-BMP-2 showed presence of new bone formation compared to blank control, which showed only small amount of callus formation
Raina et al. (2020) [25]
  • (1)

    Untreated (blank control)

  • (2)

    GM

  • (3)

    GM + ZA

  • (4)

    GM + ZA + rhBMP-2
  • (1)

    GM: GM + 20 μL saline solution

  • (2)

    GM + ZA: GM + 150 μg of ZA (concentration 4 mg/5 mL) mixed in 112.5 μL saline

  • (3)

    GM + ZA + rhBMP-2: GM + 150 μg of ZA + 150 μg of rhBMP-2 (concentration 0.5 mg/mL)

 Implantable bone bandage The volumes of callus in all GM-treated groups were higher compared to the blank control, especially in the presence of rhBMP-2 and ZA
Su et al. (2013) [32]
  • (1)

    Untreated (blank control)

  • (2)

    Scaffold only

  • (3)

    BMSCs/scaffold

  • (4)

    BMSCs/bFGF/scaffold

  • (5)

    BMSCs/BMP-2/scaffold

  • (6)

    BMSCs/bFGF/BMP-2/scaffold
  • (1)

    BMSC/scaffold: scaffold containing nHA + 1 × 107 cells/implant

  • (2)

    BMSCs/bFGF/scaffold: BMSCs/scaffold + 50 ng/mL bFGF

  • (3)

    BMSCs/BMP-2/scaffold: BMSCs/scaffold + 100 ng/mL BMP-2

  • (4)

    BMSCs/bFGF/BMP-2/scaffold: BMSCs/scaffold + 50 ng/mL bFGF + 100 ng/mL BMP-2

 Implantable scaffold All rats implanted with scaffold showed areas of new bone formation compared to the untreated rats, where none of the rats survived
Tan et al. (2012) [26]
  • (1)

    PBS (blank control)

  • (2)

    IBRC

  • (3)

    IBRC/rhBMP-2
  • (1)

    IBRC: IBRC containing nHAC

  • (2)

    IBRC/rhBMP-2: IBRC + 15 μg/mL of rhBMP-2

 Injectable hydrogel system Defects implanted with IBRC with or without rhBMP-2 showed new bone formation compared to the blank control, which did not show any bone repair
Teotia et al. (2017) [28]
  • (1)

    Blank control

  • (2)

    NC

  • (3)

    NC + ZA

  • (4)

    NC + rhBMP-2 + ZA
  • (1)

    NC: cement containing nHA

  • (2)

    NC + ZA: NC + 10 μg of ZA/disc

  • (3)

    NC+ rhBMP-2 + ZA: NC + 2 μg of rhBMP-2/disc + 10 μg of ZA/disc

 Implantable nano-cement Defects implanted with NCs with or without ZA and rhBMP-2 showed new bone formation compared to the blank control, which did not show any new bone formation

Abbreviations: nHA—nano-hydroxyapatite; PEI—polyethyleneimine; pBMP-2,BMP-2—bone morphogenetic protein-2; pVEGF—vascular endothelial growth factor; BMSCs—bone marrow mesenchymal stem cells; HAp/Col—hydroxyapatite/collagen composite; rhBMP-2—recombinant human BMP-2; PLGA/HA—apatite-coated poly(D,L-lactide-co-glycolide)/nanohydroxyapatite particulates; nHAC/PLLA—nano-hydroxyapatite/collagen/polyL-lactic acid; P17-BMP-2—BMP-2-derived peptide; GM—gelatin-nano-hydroxyapatite membrane; ZA—zoledronic acid; BMSCs—bone marrow mesenchymal stem cells; bFGF—basic fibroblast growth factor; PBS—phosphate buffer solution (pH 7.4); IBRC—injectable bone regeneration composite; NC—nano-hydroxyapatite/calcium sulphate cement.