Table 1 Design and structure-functional properties of wound dressings loaded with cell-conditioned medium
Delivery system design | Preparation | Hydrogel composition | Mean pore size, µm | Bioactive molecule release kinetics | Mechanical properties | Reference |
|---|---|---|---|---|---|---|
Soft hydrogel | Photopolymerization of hydrogel components | Gelatin methacrylate, lithiumphenyl-2,4,6-trimethylbenzoyl phosphinate (photoinitiator) | 342.3-200.2-180.4 | > 75% of protein loaded is released within 10 days | Hydrogel degradation time in PBS at 37 °C varied from 13 to 19 days; tensile strength and viscosity of the hydrogel increased with polymer concentration; the hydrogel was stable within 4–40 °C | [60] |
Solid bandage-like dressing | Ionic crosslinking and hydrogel molding followed with subsequent freeze-drying, macrophage seeding or soaking with cell secretome solution | Calcium-crosslinked alginate | 122.1 ± 43.6 | Burst release in the first 24 h, release of loaded proteins completed within 3 days | Minimal differences in bandage mass were detected during soaking in RPMI | [53] |
CM-impregnated dried alg-Ecm patches | Ionic crosslinking and hydrogel molding with subsequent drying with air and impregnation using CM | Calcium-crosslinked mixture of alginate and extracellular matrix of human lung fibroblasts | Homogenous nonporous matrix | Burst release in the first 12 h; steady-state protein quantity released within 3 days | Degradation time of 80% of hydrogel was 7 days; hydrogel is durable at 3 MPa and viscoelastic | [54] |
Soft hydrogel | Ionic crosslinking and hydrogel molding | Calcium-crosslinked alginate-gelatin-conditioned medium mixture | Homogenous nonporous matrix | Prolonged release of VEGF within 4 days | Tensile strength was 14.0 ± 0.64 MPa; elongation ratio at break point and Young’s modulus were 21.0 ± 2.5 and 2.5 ± 1.2 MPa | [55] |
Soft hydrogel | Physical crosslinking due to temperature-induced gelation, molding | Collagen-CM mixture | - | The protein released from the ASP after 24 h (incubation with type I collagenase); most of the ASP was fully digested after 8 h | - | [61] |
Soft hydrogel | Physical crosslinking due to temperature-induced gelation | CM - chitosan-collagen- β-glycerophosphate | - | - | Nonfluid gel after incubation at 37 °C; temperature-induced viscosity increase | [64] |
Soft hydrogel | Photo-initiated free-radical crosslinking | Hyaluronic acid-based hydrogel grafted with methacrylic anhydride and N-(2-aminoethyl)-4-[4-(hydroxymethyl)-2-methoxy-5-nitrophenoxy]-butanamide | - | > 60% of protein loaded is released within 16 days | The final modulus increased with the degree of methacryloyl substitution (9182 ± 558 Pa); the ultimate tensile strengths of hydrogel were determined as 86.6 ± 3.1 kPa, 145.4 ± 5.0 kPa, and 103.4 ± 1.5 kPa; the increased crosslinking density caused the hydrogel to become brittle | [63] |
Solid sponge-like dressing | Physical crosslinking, molding followed with subsequent freeze-drying | Sodium alginate | Wide mesh structure | Initial burst release, in the first 3 h (about 40% for proteins and 65% for lipids); protein and lipid release plateaued at 32 h | - | [56] |
Soft hydrogel | Physical crosslinking | Carboxymethyl cellulose | - | - | - | [72] |
Soft microstructured hydrogel | Particle in particle chemically ionic crosslinking | Soldium alginate/bioglass hydrogel with sodium alginate microparticles loaded with M2 macrophage secretome and PLGA microspheres with encapsulated pirfenidone | - | Sequential release of the encapsulated CM (95% of the cell secretome is released by day 5) and pirfenidone (95% of the encapsulated CM quantity is released by day 20) | Hydrogel was degraded to 80% after 14 days | [57] |
Soft hydrogel | Physical crosslinking, solvent-induced gelation | Bioinspired octapeptide, GV8 (Ac-GLYGGYGV-NH2); cell secretome | 10; 33 | > 50% of secretome release at days 2–3 | - | [52] |
Soft hydrogel | Ionic crosslinking and hydrogel molding | Calcium-crosslinked alginate-gelatin-CM mixture | - | - | - | [65] |
Solid sponge-like dressing | Ionic crosslinking, molding followed with subsequent freeze-drying | Genipin crosslinked collagen, CM | - | - | - | [62] |
Soft hydrogel | Physical crosslinking, temperature-induced gelation | Decellularized extracellular matrix (ECM) of porcine skin, CM | - | - | - | [71] |
Soft hydrogel | Physical crosslinking, temperature-induced gelation | Chitosan; medium from rat bone marrow MMSC | - | - | - | [59] |
Soft nano-structured hydrogel | Physical crosslinking, temperature-induced gelation | Silk fibroin self-assembled nanofibers, concentrated CM | - | TGF-β1, IGFBP-1, and PDGF-AB are release within 9 days | Viscosity increased with nanofiber concentration in hydrogel; CM addition decrease hydrogel viscosity | [69] |
Soft hydrogel | Physical crosslinking, cryo-gelation | Suckerin-silk fusion proteins, CM | 4–70; 42–206 (in case of a freeze-thawed hydrogel) | The cell secretome released by the day 18 | Viscoelastic, with a higher shear storage modulus than the loss modulus; with 90% of degradation occurring on days 13 and 18 | [70] |
Soft hydrogel patch | Physical and chemical crosslinking | Fibrinogen, chitosan, CM | 3–5 | EGF and KGF were released rapidly during a week, and then maintained a relatively stable and slow-releasing effect for up to 28 days | The Young’s modulus of elasticity in tension was 5.5 ± 1.2 MPa and tensile fracture amplitude was 44.6 ± 6.5% | [66] |
Soft hydrogel | Physical crosslinking, temperature-induced gelation | PVA, carageenan, CM | - | - | - | [67] |
Soft hydrogel patch | Ionic molding and crosslinking, punching | Calcium-crosslinked alginate | - | - | - | [58] |
Soft hydrogel | Polymer dissolution and double enzymatic and covalent crosslinking | Aldehyde-based chondroitin sulfate-dopamine-carboxymethyl chitosan | Length 131.4 ± 23.3; width 75.8 ± 5.0 | - | High plasticity; 13 s of the gelation time; withstands large elastic deformation; re-assembles after being damaged to form a complete hydrogel due to the natural dynamic; tensile strength, which is 0.72 MPa; completely degraded by day 10 | [68] |