Cage-like silsesquioxanes, particularly polyhedral oligomeric silsesquioxanes (POSSs) and double-decker silsesquioxanes (DDSQs), are hybrid organic-inorganic materials with the general formula [RSiO3/2]n (n = 4, 6, 8, 10, 12, 14, 16, 18). POSSs feature closed cages (T6, T8, T10, T12) with tetrahedral silicon vertices, while DDSQs comprise two cyclotetrasiloxane rings linked by two oxygen atoms with eight phenyl groups. Their unique Si–O bond properties (bond energy 426 kJ/mol, length 1.64 Å, 51% ionic character, Si–O–Si angle 143°) confer high thermal stability, flexibility, and biocompatibility, making them attractive as third-generation biomaterials designed to resorb and stimulate host tissue regeneration.
This narrative review consolidates selected literature on POSS- and DDSQ-based hybrid materials across three application domains: biomaterials (hydrogels, biofabrication, wound healing), flame retardant nanocomposites, and Ziegler-Natta catalysis. No systematic search strategy, inclusion criteria, or quantitative synthesis was reported.
*Biomaterials — Hydrogels:* Z. Li et al. modified 3-glycidyloxypropyl-POSS (G-POSS) with polyetheramine (PEA) and incorporated it covalently into gelatin, improving mechanical properties and thermal stability. Gelatin methacryloyl (GelMA)/quaternized chitosan (QCS)/POSS-Ac hydrogels with in-situ hydroxyapatite deposition promoted MC3T3-E1 cell adhesion, viability, proliferation, and bone defect regeneration. A POSS-P6-U2 dual-functional system with disulfide-linked PEG and 2-ureido-4[1H]-pyrimidinone groups formed a pH-responsive "living" network supporting osteogenic differentiation. PEGDA/TCS@Ag/POSS hydrogels demonstrated antibacterial skin repair capacity, while GelMA/TCS/POSS composites enabled Mg-S bonding favorable for angio- and osteogenesis.
*Biomaterials — Biofabrication:* Mahdavi et al. showed PLGA/PCL with 3–5% (w/v) POSS plus 20% (w/v) cartilage ECM produced printable cartilage scaffolds; 3% POSS gave optimal compressive modulus while 5% POSS yielded high cell viability. L. Lu et al. fabricated PLLA/POSS-(PLLA)8 artificial intervertebral discs combining electrospinning and 3D printing, mimicking annulus fibrosus. Sun et al. created 3D-printed microporous PEEK scaffolds with methacrylated chitosan/POSS, promoting osteogenic differentiation. Methacrylphenyl POSS (MP-POSS) at concentrations lower than 3 wt% formed cross-linked architectures with improved tensile and impact properties.
*Biomaterials — DDSQs:* Methacrylate-substituted DDSQ-PVA composites supported fibroblast spindle morphology, adhesion, migration, and proliferation. Incorporating glycidyl-propyl DDSQ into epoxy matrices produced self-assembled hierarchical porous films with ca. 30% increase in material strength and enhanced mouse embryonic fibroblast adhesion.
*Flame Retardants:* Effective PET composites contained 9 wt% zinc diethyl hypophosphite with 1 wt% octamethyl-POSS. A mixture of 3 wt% bisphenyl A-bis(diphenyl phosphate) and 2 wt% trisilanolphenyl-POSS improved polycarbonate flame retardancy. A combination of 7.5 wt% POSS with 22.5% intumescent flame retardant (IFR) enhanced polylactide fire resistance. POSS combined with ammonium polyphosphate in epoxy resins formed intumescent protective layers. Layer-by-layer DOPO/POSS assembly on polycarbonate, DOPO-POSS in epoxy, and oapPOSS/graphene/DOPO hybrids in polypropylene demonstrated synergistic effects. DDSQ-DOPO copolymers improved flame retardancy of PC and ABS composites, though DDSQ flame retardancy remains largely unexplored.
*Catalysis:* POSS/MgCl2 nano-aggregates with TiCl4 precatalysts enabled heterogeneous Ziegler-Natta catalysts with structural stability guaranteed by POSS nanocrystal scaffolds. Resulting polyethylene exhibited fine particle size, improved toughness, strength, and stiffness.
**Clinical Implications**
Functionalized POSS- and DDSQ-based hybrid materials offer versatile platforms for regenerative medicine, including bone defect repair, cartilage regeneration, intervertebral disc reconstruction, burn and cutaneous wound healing, and dental alveolar ridge preservation. Their capacity to support cell adhesion, proliferation, and osteogenic differentiation while providing tunable mechanical properties addresses limitations of conventional hydrogels and polymeric scaffolds. The transition to clinical use will depend on cost-effective, industrially scalable synthesis of silsesquioxane cages and innovative integration beyond simple additive use.