Table 1.
Immunomodulating GBR membranes improve in-situ bone regeneration outcomes through modulating macrophage behavior.
| studies | Animal models | Types of bone defects | GBR membranes | Macrophage behavior and bone regeneration outcomes |
|---|---|---|---|---|
| Kasai et al. (15) | rat | Calvarial bone defect | PTFE membrane; PTFE membrane loaded with carbon nanohorns |
Macrophage infiltration was rarely observed in nonabsorbable PTFE membrane. The loading of carbon nanohorns improved macrophage infiltration, thereby enhancing bone regeneration. |
| Liu et al. (6) | rat | Calvarial bone defect | Collagen membrane; 4D membrane; 4D-PDA membrane; E-PDA membrane |
Macrophage infiltration was rare and distributed thinly in collagen membrane during early stages, but it became abundant when the membrane degraded into fragments; Compared with the dense electrospun membrane, the 4D porous structure provided more space for macrophages and promoted macrophage infiltration. Dopamine coating on GBR membrane facilitated M2 macrophage transformation and inhibited M1 macrophage polarization; 4D porous structure and dopamine coating accelerated angiogenesis and osteogenesis. |
| Jin et al. (37) | rat | Calvarial bone defect | PFCH membranes with random, aligned, and latticed surface topologies |
The lattice surface was more conducive to the recruitment of macrophages and significantly upregulated the expression levels of M2 macrophage marker genes in the osteogenic microenvironment compared to random or aligned surface topologies, which facilitated growth factor secretion and osteoblast differentiation, thus inducing bone regeneration in vivo. |
| Xuan et al. (7) | rat | skull defect | Collagen membrane; EMC membrane; HIMC membrane |
HIMC membrane resembling natural bone surface, with an ordered structure and greater surface roughness, promoted M2 macrophage polarization, thus improving GBR outcomes. |
| Mathew et al. (17) | rat | Calvarial bone defect | PCL-CaP membrane; PCL-CaP membrane loaded with azithromycin |
Compared to PCL-CaP membrane, the loading of azithromycin promoted the early switch of macrophages into proregenerative M2 subtype and maintained a lower M1/M2 ratio until the late stage of bone repair. This resulted in better bone repair outcomes. |
| Chu et al. (5) | rat | Calvarial bone defect | Collagen membrane; EGCG modified collagen membrane; |
The modification with EGCG promoted M2 macrophage recruitment within the GBR membrane and bone defects, which facilitated growth factor secretion and osteoblast differentiation, thus inducing bone regeneration in vivo. |
| Liu et al. (38) | rat | Mandibular bone defect | HP membrane; HP@ 2%Mn membrane |
The loading of MnO2 was capable of catalyzing the decomposition of H2O2, decreasing M1 polarization of macrophages in bone defects and improving bone repair outcomes. |
| Yang et al. (16) | rat | Calvarial bone defect | SIS membrane; SIS/SrHA membrane; SIS/IFN-γ membrane; SIS/SrHA/IFN-γ membrane |
IFN-γ was released in bursts from membranes and stimulated transient M1 macrophage polarization during the early phase; whereas, the sustained release of strontium ions promoted M2 polarization during later stages. This resulted in sequential M1–M2 transformation and a significantly higher M2/M1 ratio, which strongly promoted vascularization and bone regeneration in situ. |
PTFE: Polytetrafluoroethylene; PGS: Poly (glycerol sebacate); PCL: Polycaprolactone; PDA: Polydopamine; E-PDA membrane: PDA-coated electrospun PGS membrane; 4D membrane: The 4D-morphing membrane composed of 3D-Printing PGS/PCL construct and electrospun PGS membrane; 4D-PDA membrane: PDA-coated 4D membrane; PFCH: Poly (lactate-co-glycolate)/fish collagen/nano-hydroxyapatite; EMC: Extrafibrillarly mineralized collagen; HIMC: Hierarchical intrafibrillarly mineralized collagen; CaP: Calcium phosphate; HP: Membranes made of a combination of hydroxyapatite nanowires (HAp NWs) and polylactic acid (PLA); SIS: Small intestinal submucosa; SrHA: Strontium-substituted nanohydroxyapatite; IFN-γ: Interferon-gamma.