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. 2021 Feb 19;11(2):530. doi: 10.3390/nano11020530

Table 2.

Preclinical in vivo studies where the implant-based delivery approach was used to deliver drugs through nano-based materials in OP condition.

Reference Aim Study Design Experimental Groups Main Characteristics of Nanomaterial Main Results
Alghamdi et al., 2014 [30] Anti-OP effect of Ti implants coated with alendronate loaded nCaP implanted in femoral condyle Male Wistar ORX rats
  • -

    Ti-non-coated;

  • -

    Ti-nCaP;

  • -

    Ti-nCaP/BP;

  • -

    Ti-BP

 Pin-shaped implants of pure Ti coated by ESD with nCaP, nCaP/BP, BP ↑%BV in Ti-nCaP/BP and Ti-BP vs. Ti-non-coated. ↑%BIC in Ti-nCaP and Ti-nCaP/BP vs. Ti-non-coated
Cheng et al., 2016 [32] Anti-OP effect of NT structures loaded with Ag and Sr (NT-Ag.Sr) on Ti implants implanted in a tibial defect Female Sprague Dawley OVX rats
  • -

    Ti;

  • -

    TiO2-NTs;

  • -

    NT10-Ag1.5Sr3;

  • -

    NT10-Ag2.0Sr3;

  • -

    NT40-Ag1.5Sr3;

  • -

    NT40-Ag2.0Sr3

NT-Ag.Sr on Ti surfaces (30 nm, 80 nm) ↑BV/TV, Tb.N, Conn.D, BIC, BA ratio, ↓Tb.Sp in all groups vs. Ti and TiO2-NTs
Ignjatovic et al., 2013 [36] Anti-OP effect of a paramagnetic Co-substituted
HA NPs implanted in an alveolar bone defect		 Female Wistar OP rats (MP and DM treated)
  • -

    HA;

  • -

    HA/Co1;

  • -

    HA/Co2 (mixed to autologous blood and plasma);

  • -

    empty defect

 Paramagnetic Co-substituted HA NPs ↑ALP in all groups vs. OP-empty defect
Luo et al., 2015 [46] Anti-OP effect of nanosized Sr-substituted apatite/polylactide loaded with rhBMP-2 implanted intramuscularly Female New Zealand OVX rabbits (MP treated)
  • -

    Healthy (Sr0%, Sr0.5%, Sr5%, Sr50%);

  • -

    OVX (Sr0%, Sr0.5%, Sr5%, Sr50%)

 Nanosized Sr-substituted apatite/polylactide loaded with rhBMP-2 ↓B% in OVX-Sr0% group vs. all OVX and healthy groups. ↑B% in OVX-Sr50% group vs. OVX-Sr0% group. ↑Ap% and ↓areas with active OBs in OVX groups vs. healthy groups
Offermanns et al., 2016 [47] Anti-OP effect of nanotopographic implants with a Sr-functionalized Ti coating (Ti-Sr-O) implanted in tibia Female Wistar OVX rats
  • -

    Ti (uncoated);

  • -

    Ti-Sr-O (2.000 nm, 1.500 nm)

 Ti-Sr-O (thickness 1.500–2.000 nm) ↑BA%, BIC% in Ti-Sr-O group vs. Ti
Qayoom et al., 2020 [48] Anti-OP effect of calcium sulfate/nHA based NC as carrier of BMP-2, ZOL, BMSCs-derived EXO, implanted in a femur defect Sprague-Dawley OVX rats
  • -

    NC;

  • -

    NC-ZOL (systemic or local);

  • -

    NC-EXO-ZOL;

  • -

    NC-BMP-2-ZOL

 NC functionalized with BMP-2, ZOL or EXO ↑mineralization, BV/TV, Tb.N, ↓Tb.Sp in all groups vs. NC. ↑peak fracture force in NC-BMP-2-ZOL vs. all groups
Shen et al., 2016 [51] Anti-OP effect of a HY-Aln/BMP-2 nanoparticles embedded into the Gel/Chi multilayers on Ti6Al7Nb surfaces (Ti6Al7Nb/LBL/N) implanted into femoral epiphysis New Zealand White OVX rabbits
  • -

    Ti6Al7Nb;

  • -

    Ti6Al7Nb/LBL;

  • -

    Ti6Al7Nb/LBL/NP

 HY-Aln NPs loaded with BMP-2a, immersed into Gel/Chi on Ti6Al7Nb ↑interfacial strength, BV/TV, Tb.Th, new bone formation in Ti6Al7Nb/LBL/NP vs. all groups
Wu et al., 2020 [56] Anti-OP effect of a poly (N-isopropylacrylamide) brush modified mesoporous HA loaded with SIM (MHA-SIM-P) on femur defect Female Wistar OVX rats
  • -

    MHA;

  • -

    MHA-SIM-P

 MHA-P NPs (4 nm pores) loaded with SIM ↑BV/TV, Tb.N, OPN, BSP and ↓Tb.Sp, OCs number in MHA-SIM-P vs. all groups
Yang et al., 2020 [57] Anti-OP effect of ZOL loaded gelatin NPs integrated porous Ti scaffold implanted in a femoral defect Female New Zealand OVX rabbits
  • -

    Ti6Al4V-ZOL-NPs (1, 10, 50, 100, 500 μmol/L)

 pDA-coated porous Ti6Al4V scaffold, integrated with ZOL loaded gelatin NPs (150 nm) ↑BV/TV in Ti6Al4V-ZOL-NPs (1, 10, 50 μmol/L) vs. OVX only
Zhang et al., 2016 [59] Anti-OP effect of HP polyplexes (PEI, PEG) loaded with miR-26a, encapsulated in PLGA MS, immobilized on NF PLLA implanted into calvaria defect Female C57BL/6J OVX mice
  • -

    PLLA coated polyplexes;

  • -

    PLLA coated HP/mi-R26a;

  • -

    PLLA with immobilized PLGA (6.5, 64-K) MS loaded with polyplexes;

  • -

    PLLA with immobilized PLGA (6.5, 64-K) MS loaded with HP/miR-26a

 HP polyplexes (PEI, PEG) (224 nm) loaded with miRNA (miR-26a), encapsulated in PLGA MS, immobilized on NF PLLA ↑BMD, BV/TV, Ob.S/BS, Ob.N/B.Pm, MAR, BFR, OCN in cell-free PLLA with immobilized PLGA (64-K) MS loaded with HP/miR-26a vs. all groups
Zhang et al., 2017 [60] Anti-OP effect of PIB nanogel containing MBG loaded with Sr in a critical-sized femur defect Female OVX rats
  • -

    Empty defect;

  • -

    PIB;

  • -

    PIB-OBs;

  • -

    PIB-Sr-MBG;

  • -

    PIB-Sr-MBG-OBs

 PIB nanogels loaded with Sr-MBG and OBs ↑BMD, BV/TV, mineralization, Col I in PIB-Sr-MBG-OBs vs. all groups. ↑OCs number in -PIB-OBs vs. all groups

Abbreviations: OP = osteoporosis; Ti = titanium; BP = bisphosphonate; nCaP = calcium phosphate nanoparticles; ORX = orchidectomy; %BIC = bone-to-implant contact percentage; HA = hydroxyapatite; OVX = ovariectomy; BV/TV = bone volume/total volume; Tb.N = trabecular number; NT = nanotubular; Conn.D = connective density; Co = cobalt; MP = methylprednisolone; DM = dexamethasone; Sr = strontium; B% = de novo bone formation; OBs = osteoblasts; O = oxygen; BA% = bone area; BV/TV = bone volume/total volume; Tb.Th = trabecular thickness; Tb.Sp = trabecular spacing; Tb.N = trabecular number; BV = volume fraction; ZOL = Zoledronate; NC = nanocement; BMP-2 = bone morphogenetic protein-2; Gel = gelatin; Chi = chitosan; SIM = Simvastatin; OPN = osteopontin; BSP = bone sialo protein; PLLA = poly(L-lactic acid); MSCs = Mesenchymal stem cells; Ob.S/BS = Osteoblast surface/bone surface; Ob.N/B.Pm = osteoblast number/bone perimeter; BFR = bone-formation rate; PIB = p(N-isopropylacrylamide-co-butyl methylacrylate); Col I = Type I collagen; OCs = osteoclasts; HP = hyperbranched polymer; MBG = mesoporous bioactive glass; BMD = bone-mineral density; NF = nanofibrous.