Table 1.
Bone adhesion tests, preclinical and clinical applications of bone adhesive materials.
| Composition of Adhesive Material | Bone Adhesion Tests |
Preclinical Studies | Clinical Studies | |||
|---|---|---|---|---|---|---|
| Type of Test | Test Substrate | Adhesion/Storage Conditions | Adhesion Strength (kPa) | |||
| Fibrin glue | pull-off | bovine cancellous bone | R.T.1, 10 min, held in compression | 5–17 [6] | • Fixation of osteochondral fractures in a dog radial head and femoral condyle model [12,13] • Fixation of osteochondral fractures in a rabbit knee model [14] • Fixation of osteochondral fractures in a rabbit lateral condyle model [15] |
• Fixation of osteochondral fractures involving proximal interphalangeal joint [16] • Fixation of fractures of intercondylar distal humerus [17] • Stabilization of bone fragments in comminuted nasal fractures [18] • Stabilization of bone fragments in inferior orbital wall fractures [19,20] • Stabilization of bone fragments in anterior wall of the maxillary sinus fractures [21,22] • Fixation of displaced comminuted fractures of the head of the radius [23] • Fixation of displaced fractures of the humeral capitulum [24] • Fixation of various chondral and osteochondral fragments in lateral femoral condyle, medial surface of patella, talar trochlea, head of radius, capitellum of humerus, MCP joint [25] • Fixation of large osteochondral fractures of the patella [26] • Fixation of osteochondral talar fractures [27] • Reattachment of the delaminated chondral surface to the subchondral bone beneath it [28] |
| pull-off | porcine cortical bone | R.T., 1–2 min, held firmly between paper towels soaked in PBS/R.T., 1 h | 11 [29] | |||
| Gelatin/resorcinol/formaldehyde (GRF) | pull-off | porcine bone | R.T., 1–2 min, held firmly between paper towels soaked in PBS/R.T., 1 h | 200 [29] | – | – |
| Carbodiimide crosslinked gelatin and alginate loaded with hydroxyapatite (HA) and tricalcium phosphate (TCP) | pull-off | cortical parts of bovine femurs | 37 °C, 30 min, 100% humidity, under load | 26–71 [30] | – | – |
| Tyrosinase modified soybean protein | lap shear | porcine bone | R.T., 20 min, fixed with rubber band/25 °C, 15 min, in calcium chloride followed by 25 °C, 48 h in incubator | 400 [31] | – | – |
| Covalently (glutaraldehyde) and/or ionically (CaCO3/hydroxyapatite)-crosslinked chitosan-based hydrogels | pull-off | cancellous bovine humerus bone | R.T., 24 h/no storage or 37 °C, 5 min, in water | 72–260 [32] | – | – |
| Glutaraldehyde crosslinked chitosan | pull-off | cancellous bovine humerus bone | R.T., 24 h or 37 °C, 24 h, in water |
Dry 200 ± 60 [33] wet 24 ± 3.6 [33] | – | – |
| lap shear | dry 220 ± 90 [33] wet 31 ± 7 [33] |
– | – | |||
| Catechol−chitosan/zeolitic imidazolate framework-8 nanoparticles | pull-off | bovine cortical bone | Pressured, 37 °C, overnight, in PBS | 310–770 [34] | • Stabilization of bone graft material in a rat cranial model [34] | – |
| DOPA-functional two component system based on chitosan and dextran or starch | tear-off | bovine cortical bone | 37 °C, 3 h, in physiologic saline solution under constant pressure | 180–410 [35] | – | – |
| Oxidized dextran-gelatin network/amine-modified mesoporous bioactive glass nanoparticles | pull-off | porcine femur bone | 37 °C, 10 min/37 °C, overnight, in PBS | 127 ± 10 [36] | • Fixation of a comminuted radius fracture in a rabbit model [36] | – |
| lap shear | 108 ± 8 [36] | |||||
| Ostamer (trihydroxy resin/diisocyanate polyurethane) | – | – | – | – | • Fixation of defects in dog radius and femur models [37] | • Acute fractures of the tibia, non-unions and pathologic fractures of the femur [37] |
| Various polyurethane- based adhesive formulations | pull-off | bovine rib | no information | 1340 ± 106 [38] | • Fixation of bones in a frog hind limb tarsus model [39] • Reunion of a bone fragments in a dog tibia model [40] • Fixation of osteotomies in a rabbit ilium model [41] |
– |
| pull-off | porcine rib | 37 °C, 24 h, wrapped in phosphate buffered saline-soaked gauze | 690–1250 [41] | |||
| Kryptonite (castor oil derived polyurethane/calcium carbonate) | – | – | – | – | – | • Augmentation conventional wire cerclage in primary sternal closure [[42], [43], [44]] • Late sternal re-entry after use of Kryptonite [45] • Fixation of vertebral fractures [46] • Sealing of retrograde cavities [47] • Midface reconstruction [48] |
| N-butyl-2-cyanoacrylate (Histoacryl) | pull-off | compact femoral or tibial bovine bone | R.T., 3 min under pressure/R.T. or 37 °C, 24 h, in water | 12100 [49] | – | – |
| Isobutyl-2-cyanoacrylate (Bucrylat) | 7900 [49] | |||||
| Ethyl-2-cyanoacrylate | 7400 [49] | |||||
| N-butyl-2-cyanoacrylate | pull-off | human cadaver parietal bone | 37 °C, 10–20 min, under humid conditions | 2180 ± 700 [50] | • Fixation of mandibular angulus fracture in an ovine model [51] • Fixation of osteotomies in the craniofacial skeleton of a miniature pig craniofacial model [52] • Fixation of osteotomies using bone grafts in rabbit thoracic limb model [53] • Fixation of fractures in a rat segmental tibia model [54] • Fixation of displaced zygomatic bone fractures in a rabbit model [55] • Fixation of the craniofacial skeleton in a rabbit model [56] • Fixation of osteotomized cranial bone fragments in a pig model [57] • Fixation of mandibular osteotomies in a rabbit model [58] • Fixation of onlay cortical bone block grafts on mandibles in a rabbit model [59] • Fixation of osteotomies in cadaver parietal bone segments in a sheep model [60] |
• Fixation of mandibular fractures [61] • Fixation of a talar osteochondral fracture [62] • Stabilization of bone flaps in the skull [63] • Adjunct to interosseous wiring and miniplate fixation in facial bone fractures (comminuted fractures of the orbital roof, frontal sinus, maxillary anterior wall and a skull defect) [64] • Fixation of fractures in the orbital-maxillo-zygomatic complex [65] |
| lap shear | 1970 ± 220 [50] | |||||
| 2-octyl-2-cyanoacrylate | pull-off | human cadaver parietal bone | 37 °C, 10–20 min, under humid conditions | 1080 ± 220 [50] | • Autogenous bone graft fixation of calvaria in a rat model [66] • Fixation of osteochondral plugs in a rat hind leg model [67] |
– |
| lap shear | 1080 ± 140 [50] |
|||||
| Ethyl-2-cyanoacrylate (Super Bonder®) | lap shear | pig jaw samples | R.T., 20–30 s, under compression/R.T., 60 s | 1160 ± 430 [68] | – | – |
| N-butyl-2-cyanoacrylate (Histoacryl®) | 1220 ± 500 [68] | |||||
| PMMA | pull-off | bovine cancellous bone | R.T., 10 min, held in compression | 1010 [6] | – | – |
| PMMA | pull-off | bovine femoral or tibial bone | R.T., manually pressed | 350 [69] | – | – |
| Various lactide-methacrylate systems | – | – | – | – | • Augmentation of K-wires in stabilization of monocondylar osteotomy of the distal femur in a rabbit model [70] • Stabilization of osteotomies of the metaphyseal ulna in a ovine model [71] • Augmentation of screws in the stabilization of lateral tibial condyle in an ovine model [72] |
– |
| Lactide-methacrylate systems reinforced with inorganic particles | lap shear | bovine bone | 25 °C, 1–10 min | 3100–13900 [73] | • Reimplantation of proximal tibia and distal femur in a rabbit model [74] | – |
| 25 °C, 1–10 min/37 °C, 24 h, SBF | 300–7700 [73] | |||||
| Crosslinked polypropylene fumarate (PPF)/HEMA/nanobioactive glass particles | lap shear | sheep rib trabecular bone | R.T., 2 min/37 °C, 1 d, wrapped in PBS-soaked gauze | 6000 - 9000 [75] | – | – |
| 4-META/MMA/TBB cement | pull-off | human femur -metal adherend | R.T., 30 min/37 °C, 24 h, in water | > 7000 [76] | • Stabilization of Ti implant-tibial bone interface in a dog model [77] • Stabilization of stainless-steel implant- femoral bone interface in a rabbit model [78] |
– |
| Clearfill New Bond (Bis-GMA, HEMA, MDP, hydrophobic monomer, initiator) | pull-off | porcine mandible bone | Photopolymerized for 60 s | 6390 [79] | – | – |
| Adper PLP/Relyx, Optibond/Maxcem, AdheSE/Multilink, G-Bond/GCem | lap shear | bond porcine mandibular bone | Cured according to the manufacturers' specifications/R.T., 15 min | 2100–4830 [80] | – | – |
| Alendronate-functional poly (2-oxazoline) dual crosslinked hydrogel | pull-off | porcine bone | R.T., 2 min, pre-wetted with a PBS-soaked gauze | dry 116 wet 47 [81] | – | – |
| Interpenetrating network of PEGDMA matrix/isocyanate functional star-shaped prepolymers/biodegradable ceramic fillers | lap shear | bovine femur | 1 h/37 °C, 1 d or 7 d, PBS | 170–250 [82] | – | – |
| DOPA and l-lysine containing biomimetic copolypeptides | lap shear | porcine bone | 25 °C, 12 h or 37 °C, 0.5 h followed by 37 °C, 12 h, in water | dry 295 wet 155 [83] |
– | – |
| DOPA-functional polypeptide−pluronic−polypeptide triblock copolymers | pull-off | porcine femur bone | 2 h–24 h | 50–290 [84] | • Fixation of tibial osteotomy in a rat model [84] | – |
| DOPA-functional polypeptides | pull-off | porcine bone | 24 h | 600 [85] | • Fixation of tibial osteotomy in a rat model [85] | – |
| DOPA-functional hyperbranched polypeptides | pull-off | porcine femur bone | 24 h | 790 [86] | • Fixation of tibial osteotomy in a rat model [86] | – |
| DOPA-functional chitosan-graft-polypeptides | pull-off | porcine femur bone | 24 h, 37 °C, in PBS | 640 [87] | • Fixation of tibial osteotomy in a rat model [87] | – |
| Lap shear | Aluminium adherend | 3000 [87] | ||||
| DOPA and citric acid functional PEG/hydroxyapatite | lap shear | chicken bone | R.T., 2 h, wet | 110 [88] | • Fixation of comminuted radial fracture in a rabbit model [88] | – |
| R.T., 48 h, dry | 740 [88] | |||||
| Catechol-functional methacrylate/N-vinylcaprolactam copolymer-based hydrogels | pull-off | chicken bone plates | 60 °C, 2 min/5 h or 18 h | 5 h 776 ± 87 18 h 696 ± 91 [89] | – | – |
| Adipic dihydrazide-modified poly (l-glutamic acid)/catechol and aldehyde dual modified alginate | – | porcine bone | 37 °C, 24 h in 0.01 M PBS | Not quantified. Survived flushing for 5 min under the water [90] | – | – |
| Catechol-functional hyperbranched PEG-based coacervates | lap shear | bone (not specified) | R.T., 12 h, in water | 270 [91] | – | – |
| Synthetic polyelectrolytes condensed into liquid complex coacervatesSynthetic polyelectrolytes condensed into liquid complex coacervates | lap shear | Wet bovine cortical bone | 37 °C, 24 h, 100% humidity | 100 [92] | – | – |
| Complex coacervates made from amine modified gelatin/polyphosphodopamide/Ca2+ or Mg2+ | lap shear | wet aluminium adherend | 37 °C, 24 h, in water | 760 [93] | • Fixation of cranial fractures in a rat model [94] | – |
| Phosphoserine-valine poly (ester urea) copolymers | lap shear | cortical bovine bone | R.T, 1 h & 75 °C, 24 h/kept in PBS-soaked gauze, 37 °C, 24 h & at 95% humidity, 2 h | 400 ± 200 [95] | – | – |
| aluminium adherend |
R.T, 1 h followed by 75 °C, 24 h | 1170 ± 190 [95] | ||||
| Biomimetic polypeptide | pull-off | bovine bone | 3 days at 23 °C | 696 [96] | – | – |
| Phosphoserine modified tetracalcium phosphate cement | lap shear | cortical & cancellous porcine bone | R.T., 10 min/kept in PBS, 37 °C, 48 h | > 1000 [97] | • Fixation of critical size distal femur defects in a rabbit model [97] • Stabilization of dental implants in oversized osteotomies in a canine model [98] • Cranial bone flap fixation in an ovine model [99] |
– |
| porous and polished titanium | R.T., 10 min/kept in PBS, 37 °C, 48 h | > 3000 [97] | ||||
| Phosphoserine modified α-tricalcium phosphate cement | lap shear | cortical bovine bone | in water, 37 °C, 24 h |
4000 [100] | • Development of a preclinical murine distal femoral bone model for evaluation of adhesives in osseous and osteochondral tissue reconstruction [101] • Subcutaneous implantation in a rat model to assess in vivo safety [102] |
– |
| Modified magnesium phosphate cement: farringtonite/phytic acid | lap shear | bovine cortical bone | R.T., 10 min | 1220 ± 410 [103] | – | – |
| R.T., 10 min/37 °C, 7 d, PBS at | 810 ± 120 [103] | |||||
| Osteocrete: magnesium phosphate cement | – | – | – | – | • Tendon-to-bone healing in anterior cruciate ligament reconstruction in a rabbit model [104] • Fixation of Y-shaped osteotomy of the second and fourth metatarsal bones in a horse model [105] • Stabilization of bone-screw interfaces in the third metacarpal and third metatarsal bones in a horse model [106] • Stabilization of dental implants in a dog model [107] • Treatment of critical-sized skull defects and cementing bone flaps in rabbit models [108] • Tendon-to-bone healing in a dog model [109] |
– |
| Aluminium-free glass ionomer cements | – | – | – | – | • Fixation and stabilization of sternum, distal radius and percutaneous upper extremities in human cadaveric models [110,[111], [112], [113], [114]] | – |