1. Introduction

Tissue engineering, which uses scaffolds, cells, and bioactive molecules to create functioning tissue and organs, has become a game-changing technique in regenerative medicine (Sharma and Shukla 2024). Three-dimensional porous scaffolds, which mimic the natural extracellular matrix and offer mechanical support, structural integrity, and a favorable milieu for cellular functions like adhesion, proliferation, and differentiation, are essential to this field (Tan et al. 2022).

Recent developments emphasize the value of hierarchically porous scaffolds that combine macro and meso-scale components into a single structure. It has been demonstrated that, in comparison to single-scale scaffolds, multi-scale architecture significantly improves biological outcomes, cell migration, angiogenic response, and osteogenic differentiation.

Natural polymers like collagen and silk have inherent biocompatibility and are bifunctional for cellular attachment, therefore their composition has an equally important impact on scaffold performance (Effect 2024). However, their inadequate mechanical strength is a common problem, particularly for tissues that sustain loads. Because of their superior mechanical properties and ability to manage degradation rate, synthetic polymers such as polycaprolactone (PCL), polylactic acid, and poly are frequently used. Glass confirms, osteo-conductivity, structural rigidity, hydroxyapatite or bioactive, and stimulatory enhancers for bone tissue regeneration are among the Edison of bioactive ceramics.

The creation of 3D porous scaffolds is essential to tissue engineering because it promotes the regeneration of diseased or injured tissue (Glass 2023). The approach used in the construction of these scaffolds, which incorporates elements from engineering, biology, and materials sciences, is crucial to their success. In order to promote cell adhesion, nutrient flow, and mechanical stability, the procedure starts with the digital design of the scaffold architecture, where factors like pore size, shape, and interconnectivity are optimized (Multiscale 2023). After the design, an appropriate biomaterial is chosen based on its structural qualities, biodegradability, and compatibility with living tissue.

The scaffold is then built using sophisticated fabrication methods such 3D printing, bioprinting, and electrospinning in accordance with the specified geometry. Following fabrication, the scaffold is subjected to biological processing such as cell seeding and in vitro culture in order to assess its cellular response. 3D porous scaffolds have developed from basic structural support to multipurpose platforms that can react to biological cues, transport medicinal agents, and integrate with digital health systems because to advancements in materials sciences and scaffold technologies (Bhardwaj et al. 2023).

2. Classification of 3D Scaffold in Tissue Engineering.

2.1. Geometry / Architecture

1.       Macroporous (porous, sponge, or foam): Connected pore networks (~>100 µm) promote vascular development, nutrient exchange, and ECM deposition (Chinnasami et al. 2023).

2.       Micropores (less than 10 µm): Promote cellular adherence, which is essential for early tissue integration

3.       Mesoporous (less than 100 nm): Encourages signalling and protein adsorption inside the scaffold.

4.       Hierarchical Pores: These pores combine porosity at the macro, micro, and mesoscales to maximize mechanical stability and nutrient flow (Zhang et al. 2021).

2.2. Composition

1.       For improved performance, natural and synthetic polymers—such as collagen, gelatin, and PCL, PLA, and PLGA—are utilized separately or in composites with ceramics.

2.       Better mechanical strength and osteo conductivity are provided by ceramic and bioactive composites (such as polymer/ceramic mixes) (Bhardwaj and Jangde 2023).

2.3.   Fabrication Techniques

1.       Conventional (Macro-Level Approaches): Phase separation, freeze-drying, gas foaming, and solvent casting/ particulate leaching produce macropores but have little control over micro/nano structures; they are frequently used to adjust porosity and control pore architecture (Abdelaziz et al. 2023).

2.       Additive/High-Precision Methods: Hierarchical, multi-scale pore architectures and exact geometric control are made possible by 3D printing/FDM, electrospinning, and templating processes.

2.4 Pore-Scale Classification

Defined by average pore size:

1.       Macroporous (>100 µm): Encourages vascularization and cell infiltration; typical ideal ranges for osteogenesis are 200–350 µm.

2.       Micropores (less than 10 µm): Enhance mass transfer and cell adhesion.

3.       Mesoporous (less than 100 nm): Facilitates protein adsorption and biochemical cues.

4.       Hierarchical: Combines several scales for combined mechanical and biological advantages (Nikolova et al. 2019).

3.  Materials Used for Developing Scaffold

Patients with osteoporosis or cancer typically have inadequate bone metabolism, so the source of the scaffold material should be determined by these conditions. In scaffold tissue engineering, a variety of materials are employed, including carbon-based nanomaterials, bio-ceramics, natural and synthetic polymers, and biodegradable metals (Abdelaziz et al. 2023; Jangde and Singh 2016).

3.1. Natural Polymers Used in Tissue Regeneration

1.       Cellulose: Cellulose is the perfect substance for tissue development. Among its many qualities are its low cost, biocompatibility, and biodegradability. It is already employed as a scaffolding material in bone tissue engineering, wound healing, cartilage tissue regeneration, and endothelial cell differentiation. Numerous biological applications make extensive use of scaffolds made from bacterial cellulose. Recent studies have shown how well the material performs in terms of biocompatibility or cell development (Abdelaziz et al. 2023).

2.       Chitin and Chitosan: Because of its exceptional qualities, including non-toxicity, biocompatibility, and biodegradability, and metal ion chelation, chitin offers a wide range of biomedical uses in tissue engineering. It is a viable choice for the regeneration of skin tissue. Moreover, it is utilized in bone, cartilage, and dental implants (Krishani et al. 2023; Babilotte et al. 2021).

3.       Alginate: Alginate is a promising material for cartilage tissue engineering scaffold development due to its biocompatibility, biodegradability, easy production process, and adjustable mechanical properties. Utilized in drug delivery systems, blood vessel formation support, bone injury healing, cartilage regeneration, and scaffolds for cell development (Bhardwaj and Jangde 2024).

4.       Hyaluronic Acid: this substance is frequently utilized as scaffolds in a variety of forms, including injectable hydrogels, sponges, cryogels, and hydrogels. The regeneration of cartilage, which is important for tissue repair, was accomplished using a scaffold material made of collagen and hyaluronic acid (Sun et al. 2022; Jangde et al. 2022).

3.2.  Synthetic Polymers Used in Tissue Engineering

1.       PLGA (polylactic-co-glycolic acid): This biomaterial was created to create 3D-printed scaffolds for bone tissue engineering. It is composed of medical-grade polylactic-co-glycolic acid (PLGA) combined with 5% or 10% (w/w) hydroxyapatite nanoparticles (NHA). Initially, PLGA, PLGA-HA 5%, and PLGA-HA 10% printing quality were assessed (Khute and Jangde 2023).

2.       PCL (polycaprolactone): The hydrophilic characteristic of PLA inhibits cell adhesion, proliferation, and differentiation, and PCL blends effectively promote cranial bone repair. By adding bio-ceramics, which improve mineralization and compressive strength, this polymer's mechanical strength can be increased. Similar to this, adding metallic nanoparticles (NPs) like gold, silver, and platinum raises the PLA-based composites' thermal conductivity, which eventually enhances biodegradation (Su et al. 2023).

3.       Polyvinyl alcohol (PVA): PVA was chosen because of its many good qualities, which make it a good matrix for mechanical and other applications. These qualities include high optical transmission, water solubility, non-toxicity, biocompatibility, thermal stability, and non-corrosiveness.

4.       PU (Polyurethanes): These polymeric materials have a vast array of chemical and physical properties since their structure or manufacture process can be changed. They can therefore be modified to meet the many needs of modern technologies, including those of fibers, adhesives, coatings, thermoplastics, and thermoplastic elastomers. On the other hand, biodegradable polyurethanes (PUs) have been investigated recently for use in biomedicine, particularly in tissue engineering and regenerative medicine. Biodegradable PUs are specifically designed to undergo regulated, slow breakdown in vivo and to promote the formation of new tissue, in contrast to long-term biostable implants (Wang et al. 2023; Sun et al. 2025).

3.3.  Ceramics/Bioactive Used in Tissue Regeneration.

1.       HA or TCP: Because of their availability, osteo conductivity, and suitable biocompatibility, calcium phosphates (Ca Ps), one of the primary components of bone, show a suitable potential to be involved in the bone rebuilding process. Ca Ps has been effectively employed in dentistry and orthopaedics to repair craniomaxillofacial tissues, correct abnormalities, and more (Yang et al. 2024).

4.       Methods of Scaffold Fabrication:

The scaffold is constructed utilizing a variety of techniques after the design and material are finalized. Traditional methods include gas forming and electrospinning (for nano-fibrous scaffolds), liquid casting and particle leaching (for random porosity), and freeze drying (perfect for natural polymers). However, the capacity to create complex and customized structures with exact pore control has made additive manufacturing techniques like 3-D printing and 3-D bioprinting the most popular. Layer-by-layer deposition of bio inks containing growth and cell factors in bioprinting enables real-time cell integration during scaffold creation. Printing, temperature, nozzle speed, and layer thickness are among the parameters that are optimized to prevent cellular harm (Wang et al. 2023; Zhang et al. 2023).

5.  Future Prospects

3D porous scaffolds' future is fast growing beyond conventional biomedical applications thanks to interdisciplinary advancements in additive manufacturing, biology, and material science. In the biomedical field, next-generation scaffolds are being developed to transport drugs in a stimuli-responsive manner, allowing bioactive compounds to be released in reaction to environmental cues like temperature, pH, or enzymes. These smart scaffolds' localized and controlled effect makes them very intriguing for cancer treatment and chronic wound care. 3D porous scaffolds are becoming more popular in environmental sectors outside of medicine, particularly as filtration and adsorption systems for water purification. Sustainable, biodegradable polymers are being used to create environmentally friendly solutions, and their high surface area and tuneable porosity make them appropriate for absorbing organic contaminants and heavy metals. Additionally, scaffold-based biosensors are being developed to detect toxins or biomarkers in real time by utilizing their structural stability and compatibility with functional biomolecules. Energy storage and conversion are other recent innovations. Batteries, super capacitors, and fuel cells use porous carbon or metal-organic frameworks made from scaffold technology.

Conflict of interest Author declares that there is no conflict of interest.

Funding information not applicable.

Ethical approval not applicable.

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