Table 1: Scaffolds’ fabrication techniques in tissue engineering applications.

MethodPolymersUnique factorsApplication

Biodegradable porous scaffold fabrication

Solvent casting/salt leaching method [3537]Absorbable polymer (PLLA, PLGA, collagen, etc.)Biodegradable controlled porous scaffoldsBone and cartilage tissue engineering
Ice particle leaching method [3840]PLLA & PLGAControl of pore structure and production of thicker scaffoldsPorous 3D scaffolds for bone tissue engineering
Gas foaming/salt leaching method [4143]PLLA, PLGA & PDLLAControlled porosity and pore structure spongeDrug delivery and tissue engineering

Microsphere fabrication

Solvent evaporation technique [4446]PLGA, PLAGAHigh-density cell culture, due to the extended surface areaBone repair
Particle aggregated scaffold [4749]Chitosan, HAPHigh mechanical stabilityBone, cartilage, or osteochondral tissue engineering
Freeze drying method [5052]PLGA, PLLA, PGA, PLGA/PPF, Collagen, and Chitosan3D porous sponge structure, durable and flexibleTissue engineering scaffolds
Thermally induced phase separation [53, 54]PEG, PLLAHighly porous scaffold for cellular transplantationComplicated shapes for tissue engineering applications

Injectable gel scaffold fabrication

Ceramic-based injectable scaffolds [5557]CP ceramics, HAp, TCP, BCP, and BGPorosity and bioresorbabilityCartilage tissue engineering
Hydrogel-basedinjectable scaffolds [5860]Hydrophilic/hydrophobic diblock and triblock copolymer combinations of PLA, PGA, PLGA, and PEG. Copolymers of PEO and PPO and polyoxamer. Alginates, collagen, chitosan, HA, and fibroinBiomimetically, exhibit biocompatibility and cause minimal inflammatory responses, thrombosis, and tissue damageCartilage, bone tissue engineering, and drug delivery

Hydrogel scaffold fabrication

Micromolding [6163]Alginate, PMMA, HA, PEGMicrogels, biologically degradable, mechanical and physical ComplexityInsulin delivery, gene therapy, bioreactor, and immunoisolation
Photolithography [6466]Chitosan, fibronectin, HA, PEG, PNIAAm, PAA, PMMA, PAam, and PDMAEMMicrowells, microarrays, controlled size and shapeMicrodevices, biosensors, growth factors, matrix components, forces, and cell-cell interactions
Microfluidics [6769]PGS, PEG, calcium alginate, silicon and PDMSMicrobeads, microrods, valves, and pumpsSensing, cell separation, cell-based microreactors, and controlled microreactors,
Emulsification [7072]Gelatin, HA, and collagenMicrogels, microsensors, cell-based diagnosticsSustainable and controllable drug delivery therapies

Acellular scaffold fabrication

Decellularisation process [7375]Biological tissuesRetain anatomical structure, native ECM, and similar biomechanical propertiesTissue engineering

Keratin scaffold fabrication

Self-assembled process [7678]KeratinBiocompatibilityDrug delivery, wound healing, soft tissue augmentation, synthetic skin, coatings for implants, and scaffolds for tissue engineering

Fibrous scaffold fabrication

Nanofiber electrospinning process [7981]PGA, PLA, PLGA, PCL copolymers, collagen, elastin, and so forthHigh surface area, biomechanical, and biocompatibilityDrug delivery, wound healing, soft tissue synthetic skin, and scaffolds for tissue engineering
Microfiber wet-spinning process [8284]PLGA, PLA, chitosan, and PCLBiocompatible fibres with good mechanical propertiesSolar sails, reinforcement, vascular grafts, nonwetting textile surfaces, and scaffolds for tissue
Nonwoven fibre by melt-blown process [8587]Polyesters, PGA, and PDOSubmicron fiber size, highly porous scaffoldFiltration, membrane separation, protective military clothing, biosensors, wound dressings, and scaffolds for tissue engineering

Functional scaffold fabrication

Growth factor’s release process [8890]Collagen, gelatin, alginate, chitosan, fibrin, PLGA, PLA, and PEGMembranes, hydrogels, foams, microsphere, and particlesAngiogenesis, bone regeneration, and wound healing

Ceramic scaffold fabrication

Sponge replication method [9193]PU sponge, PVA, TCP, BCP or calcium sulfateInterconnected porous ceramic scaffoldsBone tissue engineering
Simple calcium phosphate coating method [9496]Coating on: metals, glasses, inorganic ceramics and organic polymers (PLGA, PS, PP, silicone, and PTFE), collagens, fibres of silk, and hairsImprove biocompatibility or enhance the bioreactivityOrthopedic application

Automation and direct organ fabrication

Inkjet printing process [97100]Sodium alginateTo build complex tissues composed of multiple cell types (Hydrogel scaffold)Biosensor development, microdeposition of active proteins on cellulose, biochips and acellular polymeric scaffolds
Melt-based rapid prototyping process [101, 102]Biodegradeable polymers or blendsComplex 3D solid object, good mechanical strengthHoney comb structure scaffold, hard-tissue scaffolds
Computer-aided design (CAD) data manipulation techniques [103105]Design and fabrication of patient-specific scaffolds and automated scaffold assembly algorithmDevelop a program algorithm that can be used to design scaffold internal architectures
Organ printing [106, 107]Tubular collagen gelLayer by layer deposition of cells or matrixTo print complex 3D organs with computer-controlled,

Scaffold sterilization

Ethylene oxide gas (EOG) [108110]For degradable polymers and porous scaffolds, high penetration ability, and compatibilityAbsolute freedom from biological contamination in scaffolds
Gamma-radiation sterilization [111113]Proven process is safe, reliable, and highly effective at treating single-use medical devicesSurgical disposables: surgical sutures, bandages, dressings, gauge pads, implants
Electron beam radiation [114116]Compatibility, low penetration, in line sterilization of thin productsCommercially successful technology for sterilizing a variety of disposable medical devices with a wide range of densities
Dry-heat sterilization [117, 118]Efficacy, speed, process simplicity, and lack of toxic residuesHeat is absorbed by the exterior surface of scaffold and then passed inward to the next layer
Steam sterilization [119, 120]Removal of all contamination, and scaffold can be reusedPorous scaffold for living cell immobilization