Table 1.
The most recent studies of cellular and acellular 3D porous scaffold strategies for TE purposes.
| Technology | Materials | Cells/Growth Factors | Outcomes | Application | Ref. |
|---|---|---|---|---|---|
| Freezing and lyophilization | Collagen (Col)/carbon nanotube (CNT)/chitosan (CS)/hydroxyapatite (HAp) | - | Increased hydrophilicity from 87.8° to 76.7° and improved mechanical properties of the composite scaffolds compared to Col (211 kPa), CS (284 kPa), Col/CNT (311 kPa), and Col/CNT/CS (524 kPa) scaffolds | Bone tissue engineering | [129] |
| Na-alginate /hydroxyethylcellulose /HAp | - | After loading with Hap, the mechanical properties of the scaffolds increased deformation energy and rigidity gradient (19.44 ± 0.85 Pa), with bioactivity and biocompatibility in vitro and in vivo (implanted in femur of adult male Wistar rats for 6 weeks) | [80] | ||
| Collagen from shark skin/ CaPs from shark teeth | Saos-2 cells seeding | Use of EDC/NHS crosslinking increased the attachment and proliferation of osteoblast-like cells | [82] | ||
| Silk fibroin and β-tricalcium phosphate (TCP) | Human adipose stem cells (hASCs) seeded on the scaffolds | Highly interconnected macroporosity.; significant responses of hASCs proliferation and differentiation when varying the ionic dopants in the scaffolds | [64] | ||
| Collagen and denatured collagen (DCol) | Rabbit chondrocytes seeding | Adhesion, proliferation, and re-differentiation of chondrocytes by Col scaffolds with triple helix and the regeneration of cartilage defects, compared with the DCol scaffolds | Cartilage tissue | [130] | |
| PLLA, PCL, and collagen type I | Adipose tissue-derived mesenchymal stem cells seeding | Mechanically stronger mesh support, provided by PCL-PLLA and cell adhesion, and tissue formation promoted by the collagen type I microsponges | Skin | [131] | |
| Silk fibroin | - | Elastic modules of the scaffolds between 100 and 900 kPa | n.d. | [132] | |
| Decellularized extracellular matrix (dECM)/gelatin/chitosan | rat BMSCs seeding | Enhanced elastic modulus, no cytotoxicity, and enhanced proliferation | Meniscus tissue | [17] | |
| bovine small intestinal submucosa (bSIS) layers/HAp microparticles/PCL | rat BMSCs seeding | Enhanced cell proliferation and osteoblastic differentiation within 21 days. Maximum strength similar in cell-laden scaffolds and cell-free scaffolds in wet conditions. | Bone | [19] | |
| Robocasting | Biphasic CaP doped with Sr and Ag | MG-63 cells | Different pore sizes with compressive strengths comparable to cancellous bone. Sr and Ag improved the mechanical strength and cell proliferation and granted good antimicrobial activity against Staphylococcus aureus and Escherichia coli | Bone tissue engineering | [117] |
| Biphasic CaP and chitosan | hDNFs (human dermal neonatal fibroblasts) | Produced levofloxacin loaded scaffolds without the sintering step. The antibiotic was not degraded during the fabrication process and its bactericidal efficacy was preserved | [119] | ||
| 3D bioprinting | PCL and bioactive borate glass | hASCs-laden | Controlled release of bioactive glass; more than 60% viable hASCs on the scaffolds after 1 week of incubation. | Bone tissue engineering | [133] |
| Polycaprolactone (PCL) | Saos-2 cells seeding | The non-orthogonal structures showed higher E moduli than the orthogonal one, with a positive influence on the biological performance of the cells; higher values for the mineralization, activity of osteogenic-related genes, and deposition of the mineralized matrix | [104] | ||
| Alginate/alginate-sulfate | MC3T3-E1 cells/BMP-2 | Alginate/alginate sulfate bioinks allowed good 3D cell printing. Improvement of the release of BMP-2 was achieved using alginate sulfate. Proliferation and differentiation of the printed osteoblasts were enhanced | [90] | ||
| GelMA and methacrylated hyaluronic acid (HA) modified with HAp | hASCs | Positive effects on bone matrix production and remodelling | [134] | ||
| Collagen/dECM/silk fibroin (SF) | MC3T3-E1 cells | High compressive modulus mainly due to the methanol-treated SF; high cellular activities in in vitro tests using MC3T3-E1 cells, induced by Collagen and dECM. | [135] | ||
| α-TCP/collagen | MC3T3-E1 cells | The scaffold showed good mechanical properties and cellular activities | [128] | ||
| collagen type I/agarose with sodium alginate | Primary chondrocytes | Addition of collagen or agarose had an impact on gelling behavior and improving mechanical strength. The collagen facilitated cell adhesion, accelerated cell proliferation, and enhanced the expression of cartilage-specific genes, (Acan, Sox9, and Col2a1) | [126] | ||
| Fibrin and wollastonite | Loaded with rabbit BMSCs | Possible extensive regeneration of both cartilage and subchondral bone induced by in vivo transplantation of the scaffolds | Osteochondral tissue | [136] | |
| Collagen | MC3T3-E1 | Cell-laden scaffold using tannic acid for crosslinking process. TA crosslinking increased mechanical properties and high cell viability | n.d. | [127] | |
| CS/PCL | dECM coating/WJMSCs seeding | Improved osteogenic differentiation in vitro and bone regenerative potential in vivo | Bone | [107] | |
| PCL/β-TCP | dECM coating/MC3T3-E1 seeding | Improved osteogenic differentiation in vitro and bone regenerative potential in vivo | Bone | [120] | |
| Laser sintering technique | PCL and HAp | - | Subchondral bone regeneration and articular cartilage formation in a rabbit model | Osteochondral tissue | [137] |
| Sol-gel method combined with 3D plotting | HAp/chitosan/silica | Mouse BMSCs seeding | Compressive strength comparable to the human trabecular bone | Bone regeneration | [138] |
| BG obtained by sol-gel method | Zein/bioactive glass (BG) | MG-63 cells seeding | Ag-doped BG scaffolds showed antibacterial properties. | [139] | |
| Electrospinning combined with electro-spraying | PCL/HAp | Murine embryonic cell seeding | High capacity to guide the migration of differentiated bone cells throughout the cavities and the ridge of the scaffolds | [140] | |
| PCL/gelatin and multi-walled carbon nanotubes (MWNTs) | Adult rabbit chondrocytes seeding | Increased hydrophilicity and tensile strength, and higher bioactivity and slower degradation rate due to presence of MWNTs; | Cartilage tissue | [141] | |
| Electrospinning | Graphene-incorporated electrospun PCL/gelatin | PC12 cells | 99% antibacterial properties against gram-positive and gram-negative bacteria. Good cell attachment and proliferation | Nerve tissue engineering | [142] |
| PCL/collagen | Human endometrial stem cells seeding | Higher wettability, attachment, and proliferation rates of hEnSCs on the PCL/collagen scaffold | Skin | [143] | |
| Polyhydroxybutyrate-co-hydroxyvaletare (PHBV) containing bredigite | - | Bredigite nanoparticles increased the mechanical properties, biodegradability, and bioactivity of the scaffolds | Bone tissue | [144] | |
| PLLA/β-TCP | hMSCs seeding | Enhanced water uptake ability, in vitro bio-mineralization, and bioactivity promoted by the incorporation of β-TCP | Bone | [145] | |
| PCL/Silk fibroin (SF) | Human fibroblast seeding | Good tensile strength, elasticity, and increased degradation rate, as well enhanced cell proliferation, with the presence of SF | n.d. | [146] | |
| Electrospinning combined with 3D bioprinting | PCL | Laden with L929 mouse fibroblasts | Multi-layered structures—3D scaffolds—with loosely packed nanofibers, with better surface wettability (when compared to the 2D scaffolds) | n.d. | [147] |
| Phase separation process | Cartilage ECM-derived/PLGA-β-TCP-collagen type I | BMSCs seeding | Enhanced OC regeneration. Chondro and osteogenic-induced BMSCs with independent environments | Osteochondral tissue | [148] |
Note: n.d.: not defined; BMSCs: bone marrow stem cells; bSIS: bovine small intestinal submucosa; ECM: extracellular matrix; HA: hyaluronic acid; hMSCs: human mesenchymal stem cells; hASCs: human adipose stem cells; HAp: hydroxyapatite; PCL: polycaprolactone; PLLA: poly-L-lactic acid; SF: silk fibroin; TCP: tricalcium phosphate.