*Review* **Development of Scaffolds from Bio-Based Natural Materials for Tissue Regeneration Applications: A Review**

**Murugiah Krishani 1,\*, Wong Yen Shin <sup>1</sup> , Hazwani Suhaimi 1,\* and Nonni Soraya Sambudi <sup>2</sup>**


**Abstract:** Tissue damage and organ failure are major problems that many people face worldwide. Most of them benefit from treatment related to modern technology's tissue regeneration process. Tissue engineering is one of the booming fields widely used to replace damaged tissue. Scaffold is a base material in which cells and growth factors are embedded to construct a substitute tissue. Various materials have been used to develop scaffolds. Bio-based natural materials are biocompatible, safe, and do not release toxic compounds during biodegradation. Therefore, it is highly recommendable to fabricate scaffolds using such materials. To date, there have been no singular materials that fulfill all the features of the scaffold. Hence, combining two or more materials is encouraged to obtain the desired characteristics. To design a reliable scaffold by combining different materials, there is a need to choose a good fabrication technique. In this review article, the bio-based natural materials and fine fabrication techniques that are currently used in developing scaffolds for tissue regeneration applications, along with the number of articles published on each material, are briefly discussed. It is envisaged to gain explicit knowledge of developing scaffolds from bio-based natural materials for tissue regeneration applications.

**Keywords:** tissue engineering; scaffold; fabrication techniques; tissue regeneration

**Citation:** Krishani, M.; Shin, W.Y.; Suhaimi, H.; Sambudi, N.S. Development of Scaffolds from Bio-Based Natural Materials for Tissue Regeneration Applications: A Review. *Gels* **2023**, *9*, 100. https:// doi.org/10.3390/gels9020100

Academic Editors: Arish Dasan, Ashokraja Chandrasekar and Nupur Kohli

Received: 30 December 2022 Revised: 19 January 2023 Accepted: 19 January 2023 Published: 23 January 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

**1. Introduction**

Tissue regeneration is a dynamic process in which the cells and their surrounding matrix interplay. Further, this process is encouraged by designing biomaterials that adapt to the local cellular signals [1]. Transplantation is the conventional method for tissue regeneration, but donor availability, pain, and risks related to graft rejection and infectious disease are some concerns [2]. Tissue engineering is a modern field that promotes tissue replacement and regeneration substitutes. It is a multidisciplinary field in which a biomaterial such as a scaffold, cells, and growth factors are combined to form a new tissue [3,4]. It also helps to overcome the problems faced during autologous and allogeneic tissue repair, such as inadequacy, donor site dejection, and unbidden immune responses [5]. The scaffold acts as a template in which cells and growth factors are implanted to imitate the extracellular matrix to maintain and restore tissue function. High porosity, pore interconnectivity, biocompatibility, biodegradability, and mechanical properties are indispensable properties that must be considered when designing the scaffold [6]. Besides blood cells, most tissue cells reside in a solid matrix known as the extracellular matrix (ECM). The ECM is an anchor for maintaining a proper structure and providing the tissue with mechanical properties and signaling molecules. Hence, the scaffold selected for engineered tissue should mimic the ECM of that specific tissue [7]. Selecting appropriate cells, isolating and expanding targeted cells, and selecting suitable biomaterial for scaffold designing are factors that thrive in tissue engineering [8]. However, a solitary polymer cannot achieve every single property of a scaffold, so the desired property can be attained by mixing it with a variety of polymers [9]. Along with the selection of material, process technique or fabrication method

Figure 1.

also provide a more significant impact on the features of the resultant scaffold [10]. This paper provides detailed information on bio-based natural materials and the fabrication techniques currently used to develop scaffolds for tissue regeneration applications. **2. Tissue Engineering**  Tissue engineering (TE) is a relatively new, unique, multidisciplinary field. It offers new hope to patients by integrating clinical medicine, materials science, cell biology and

ever, a solitary polymer cannot achieve every single property of a scaffold, so the desired property can be attained by mixing it with a variety of polymers [9]. Along with the selection of material, process technique or fabrication method also provide a more significant impact on the features of the resultant scaffold [10]. This paper provides detailed information on bio-based natural materials and the fabrication techniques currently used

#### **2. Tissue Engineering** genetics, and mechanical engineering to design bio-artificial tissues or biological substi-

*Gels* **2023**, *9*, x FOR PEER REVIEW 2 of 45

Tissue engineering (TE) is a relatively new, unique, multidisciplinary field. It offers new hope to patients by integrating clinical medicine, materials science, cell biology and genetics, and mechanical engineering to design bio-artificial tissues or biological substitutes that restore or regenerate, preserve, and improve damaged tissue or organs [3]. The three essential parameters in tissue engineering, biomaterial scaffolds, cells, and growthstimulating signals, are known as the "tissue-engineering triad," as mentioned in Figure 1. tutes that restore or regenerate, preserve, and improve damaged tissue or organs [3]. The three essential parameters in tissue engineering, biomaterial scaffolds, cells, and growth-stimulating signals, are known as the "tissue-engineering triad," as mentioned in
