Table 6.
Summary of the characteristics and main results of studies in rats (n = 6).
| Ref. | Sample Size (No. Animals) | Defect | Biomaterial(s) § | Control (Empty, DBBM, Autogenous Bone) § | Other Materials/Treatments § | Stem Cells, Drugs, GFs | Sacrifice (Weeks) |
Assessment Method(s) | Main Findings |
|---|---|---|---|---|---|---|---|---|---|
| [17] | 24 | 5 mm ϕ bilateral calvarial bone defect | (a) nHA/PLA + hBMSCs (n = 12) (b) nHA/PLA (n = 6) |
Empty (n = 12) |
(a) PLGA + hBMSCs (n = 12) (b) PLGA (n = 6) |
hBMSCs | 8, 16 | Histological analysis; histomorphometric analysis; immunohistochemistry; radiography; (weight loss profile of the scaffold after in vivo implantation intramuscularly) | Histological analysis: 8 weeks: minimal amount of bone-like tissue in defect with nHA/PLA + hBMSCs while no bone regeneration in the other groups; 16 weeks: newly formed bone in defects with PLGA + hBMSCs was larger than that in defects with nHA/PLA + hBMSCs, loose connective tissue in defects filled with scaffolds alone without cells or left unfilled; no obvious residual scaffold material in all defects both at 8 and 16 weeks. Histomorphometric analysis: new bone formation percentage in PLGA + hBMSCs and nHA/PLA + hBMSCs groups was higher than in the others (P < 0.05). Radiography: 8 weeks: no significant bone regeneration in any groups; 16 weeks: no sign of bone regeneration found in defects filled with scaffolds alone without cells. Immunohistochemical analysis: both at 8 and 16 weeks no positive staining of osteocalcin in empty defects and defects filled with scaffolds alone, while positive staining in defects filled with scaffolds seeded with cells. |
| [122] | 32 | 5 mm ϕ unilateral calvarial bone defect | (a) PLA (85% wt) + HA (15% wt) (n = 8) (b) β-TCP (n = 8) |
Empty (n = 8) |
DBM (n = 8) |
- | 4, 8 | Histological analysis; immunohistochemical analysis; micro-CT analysis; hematological analysis | Histological analysis: new bone around and in contact with the biomaterials; blank group filled with compressed fibrous-connective tissue. Immunohistochemistry: osteocalcin and type I collagen expression: PLA + HA> β-TCP > DBM; new bone %: β-TCP> PLA + HA > DBM> blank group Micro-CT analysis: new bone areas in empty control group were less than in the other implanted groups at both timepoints; the results of total degradation rates showed no significant difference between 3DP PLA/HA scaffolds and DBM scaffolds at eight weeks and β-TCP had the lowest degradation rates in all groups; Hematological analysis: leukocyte cell counts and red blood cell levels were similar in all implanted groups at the four time points (12 days, and 4, 6 and 8 weeks after the surgery). |
| [123] | 40 | 5 mm ϕ monolateral calvarial bone defect | (a) HA particles 8 mg (n = 10) (b) HA 8 mg + FS 8 mL (n = 10) |
Empty (n = 10) |
FS 8 mL (n = 10) |
- | 2, 6 | Histological analysis; histomorphometric analysis; radiography | Histological and histomorphometric analyses: 2 weeks: new bone formation from the periphery to the center of the defect; higher bone formation in the HA + FS group. 6 weeks: presence of mature newly formed bone in treated group; higher bone formation and lower connective tissue amount in the HA + FS group than in the HA group. |
| [124] | 19 | 8 mm ϕ unique calvarial bone defect | β-TCP-AE (n = 6) | Empty (n = 7) |
AE (n = 6) |
- | 4, 13 | Histological analysis; immunohistochemistry | Histological and immunohistochemical analyses: 4 weeks: both test groups showed intense inflammation-associated fibrosis; control group showed fibrous-inflammatory tissue with moderate degree of calcification; in β-TCP-AE group granulation tissue and presence of polymorphonuclear leukocytes, macrophages and fibroblasts. 13 weeks: β-TCP-AE almost totally degraded, and significantly less inflammatory cells than at 4 weeks, with presence of solid and compact bone islands; the empty control group exhibited a minimal ossification along the internal rim of the bone defect; only the β-TCP-AE group exhibited intense ossification. |
| [121] | 30 | 8 mm ϕ unique calvarial bone defect (not central) | PLGA coated with Willemite (n = 10) |
Empty (n = 10) |
PLGA (n = 10) |
- | 8 | Histological analysis; histomorphometric analysis; radiography; MSCT | Histological and histomorphometric analyses: highest bone reconstruction in animals treated with willemite-PLGA; enhanced collagen deposition willemite-PLGA group than in PLGA group. MSCT and radiography: no evidence of neo-tissue regeneration in the untreated animals; rats receiving willemite-PLGA had the highest bone regeneration; neo-tissue formation started from the periphery of the defect site toward the center. |
| [125] | 24 | bilateral femoral bone defects (3 mm in ϕ, 2 mm in depth) | (a)granules of merwinite (n = 16) (b) HA (n = 16) |
Empty (n = 16) |
- | - | 2, 8 | Histological analysis | Histological analysis: 2 weeks: no bone formation in the HA group, but presence of loose and fibrous connective tissue; connective tissue and small bone islands in merwinite group; 8 weeks: new bone until the center of the merwinite scaffold; higher bone formation and scaffold degradation in the merwinite group than in HA one; presence of irregular trabecular bone and beginning of Harvesian system formation in some areas; the control untreated group presented connective tissue both at 2 and 8 weeks and a slower healing. |
§ (n=) represents the number of sites. AE: mesoporous silica-based aerogel; β-TCP: β-tricalcium phosphate; DBM: partially demineralized bone matrix; HA: hydroxyapatite; hBMSCs: human bone marrow-derived mesenchymal stem cells; FS: fibrin sealant; MSCT: multislice spiral computed tomography; nHA: nano-HA; PLA: polylactic acid; PLGA: poly(lactic-co-glycolic acid).