Table 1.
Small molecules that have been investigated in preclincal bone regenerative engineering studies
| Small molecule | MW (Da) | Pathway | Delivery system | Loading | Animal model | Refs |
|---|---|---|---|---|---|---|
| Osteoporosis | ||||||
| Simvastatin | 418.6 | BMP/Smad | CaP nanocapsules, including deoxycholate micelles containing simvastatin | 1:3 (v/v) | Ovariectomized mouse | [52] |
| Bisphosphonate | 270 | Mevalonate | Hydroxyapatite plasma-coated titanium alloy cylinders | Soaked in 2.25 × 10−5 mol/l bisphosphonate solution for 48 h | Ovariectomized sheep | [55] |
| Long bone fractures and non-unions | ||||||
| FTY720 | 343.9 | S1P | 50:50 PLAGA-coated demineralized allograft | 1:200 (wt/wt) | Critical-sized rat tibial defect | [60] |
| Purmorphamine | 520.6 | Hedgehog | HAp beads | Soaked in 200 mM purmorphamine solution for 24 h | Fetal chick femur | [64] |
| SVAK-12 | 137.14 | BMP | Not applicable | 200 to 250 mg SVAK-12 percutaneously injected | Rat femoral fracture model | [67] |
| Simvastatin | 418.6 | BMP/Smad | Calcium sulfate/simvastatin/MSC sheet | CS mixed with 2.5 ml of 200 mg/ml simvastatin solution, then 0.5 mg simvastatin was applied in each scaffold | Rat tibia osteotomy | [95] |
| Simvastatin | 418.6 | BMP/Smad | Simvastatin/PLGA/HAp microspheres | 77.7% ± 10.3% (encapsulation efficiency) | Mouse model of gap fracture bridging with a graft of necrotic bone | [73] |
| Lovastatin | 404.5 | BMP/Smad | Lovastatin microparticle-loaded polyurethane scaffolds | 25 or 100 mg LV-MP in PBS injected into PUR scaffolds | Femoral plug defects and critical-sized segmental defects | [96] |
| Rosuvastatin | 481.5 | BMP/Smad | Adsorbable collagen sponge | Soaked in 0.1 mg/ml | Critical-sized rabbit cortical bone defect | [97] |
| Helioxanthin derivative (TH) | 348 | BMP/Smad | Tetrapod-shaped alpha tricalcium phosphate granules (Tetrabone®) | Soaked in 1 mM TH solution in DMSO overnight | Rat femur bone defect model | [98] |
| N-acetyl cysteine | 163.19 | Unknown | Commercial collagen sponge (Teruplug®) | Soaked in 5.0 mM NAC solution | Critical sized rat femur cortical bone defect | [76] |
| Spinal fusions | ||||||
| Simvastatin | 418.6 | BMP/Smad | Not applicable | Orally administered at a dose of 120 mg/kg/day | Rat spinal fusion | [80] |
| Oxysterols | 420 | Hedgehog | Adsorbable collagen sponge | Soaked in 50 ml Oxy34 or Oxy49 | Rat spinal fusion | [82] |
| Oxysterols | 420 | Hedgehog | Adsorbable collagen sponge | Soaked in 40 ml Oxy4, 18, or 21 for 1–2 h | Rat spinal fusion | [83] |
| Rolipram | 275.4 | PKA | Alginate-microfibrous patch | 25 or 50 g/ml rolipram-loaded hydrogels | Rat hemisection spinal cord injury | [99] |