Table 7.
Recent advances in 3D printed/bioprinted osteoimmunomodulatory hydrogel scaffolds for bone tissue engineering.
| Composition | Monocyte/macrophage polarization | Immunomodulatory activity | References |
|---|---|---|---|
| Glycopeptide-conjugated PCL/nHAp scaffolds | M2 phenotype | β-sheets of Glycopeptide promoted higher expression of STAT-6, IL-10, and TGF-β through ERK signaling pathway which induced the osteoblast differentiation | [228] |
| Strontium-doped nHAp/silk scaffold | M2 phenotype | Strontium induced the HIF-1α activity and promoted angiogenesis and chondrogenesis; the composite scaffold also boosted the secretion of anti-inflammatory factors and accelerated osteogenesis | [308] |
| Haversian canal mimicking bioprinting using Ca2MgSi2O7 + BMSCs (2 × 104) + RAW 264.7 cells (2 × 104) | M2 phenotype | The co-culture of BMSC/RAW 264.7 increased the expression of Arg-1, IL-10, and CD163 in RAW 264.7 cells and induced the expression of BMP-2, TGF-β1, PDGF, and VEGF; enhanced osteogenic differentiation through activation of BMP2R/Smad4 signaling | [309] |
| 3D printed β-TCP/Alginate/hyaluronic acid scaffold | M2 phenotype | The soft hydrogel promoted M2 polarization via enhancing the expression of Arg-1, IL-1ra, IL-10, TGF-β1, and VEGFA; the M2 macrophage derived exosome promoted bone regeneration through activation of Runx2, ALP, BSP, BMP-2, OCN, and OPN transcription factors | [305] |
| 3D printed PLA/MSC-exosome | M2 phenotype | 3D printed MSC-exosome loaded scaffold promoted M2 macrophage polarization and hBMSCs differentiation via immunomodulation; the MSC-exosome downregulated the pro-inflammatory factors, such as IL-1β, IL-6, iNOS, and TNF-α | [310] |
| 3D bioprinted Dox-loaded MBG/GelMA/HAMA scaffold | M1 phenotype | Enhanced activation of pro-inflammatory cytokines and anti-bacterial effect; sustained BMP-2 release boosted in vivo bone regeneration | [311] |
| 3D printed hydroxypropyl chitin/PLA/nHAp | M2 phenotype | Enhanced activation of M2 macrophages via activation of IL-10, Arg-1, CCL22, VEGFFA, PDGFB, and MMP9; robust in vivo bone regeneration in calvaria defect model through osteo-immunomodulation | [312] |
| 3D/4D printing of polydopamine (PDA)-modified collagen/PGS/PLA scaffold | M2 phenotype | PDA modification induced the M2 polarization of RAW 264.7 cells and sustained the release of anti-inflammatory cytokines for robust craniofacial regeneration | [313] |
| 3D bioprinted AgGNRs/dextran/GelMA scaffold | M2 phenotype | Activation of anti-inflammatory phenotype of RAW 264.7 cells; sustained the secretion of IL-4; enhanced osteoimmunomodulation of BMSCs; anti-bactericidal effect | [314] |
| 3D printed Ca7Si2P2O16 scaffold | M2 phenotype | The multicellular patterning of MSCs and RAW 264.7 cells exhibited a neighborhood effect; enhancement of M2 markers (CD206, Arg-1, IL-10, and IL-1ra); M2 macrophage triggered the osteogenesis via Smad/β-catenin/LRP5 signaling axis and promoted robust bone regeneration in vivo; enhancement of in vivo activation of IL-10 marker | [315] |
| QCS/GO/PDA-based 3D printed scaffold | M2 phenotype | The nanohybrid scaffold promote M2 macrophage polarization and accelerated bone and skin regeneration | [316] |
| Cryogenic 3D printing of Sr2+/Fe3+ co-substituted nHAp | M2 phenotype | The metal ions facilitated angiogenesis and osteogenesis through M2 macrophage polarization; secretion of anti-inflammatory factors (IL-10 and Arginase) | [317] |