Citation: Lázár, I.; ˇ Celko, L.; Menelaou, M. Aerogel-Based Materials in Bone and Cartilage Tissue Engineering—A Review with Future Implications. Gels 2023, 9, 746. https://doi.org/10.3390/ gels9090746 Academic Editor: Shige Wang Received: 9 August 2023 Revised: 9 September 2023 Accepted: 11 September 2023 Published: 13 September 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/). gels Review Aerogel-Based Materials in Bone and Cartilage Tissue Engineering—A Review with Future Implications IstvánLázár 1, * , Ladislav ˇ Celko 2 and Melita Menelaou 3, * 1 Department of Inorganic and Analytical Chemistry, University of Debrecen, Egyetem tér 1, 4032 Debrecen, Hungary 2 Central European Institute of Technology, Brno University of Technology, Purkynova 656/123, 612 00 Brno, Czech Republic; ladislav.celko@ceitec.vutbr.cz 3 Department of Chemical Engineering, Cyprus University of Technology, 30 Arch. Kyprianos Str., Limassol 3036, Cyprus * Correspondence: lazar@science.unideb.hu (I.L.); melita.menelaou@cut.ac.cy (M.M.) Abstract: Aerogels are fascinating solid materials known for their highly porous nanostructure and exceptional physical, chemical, and mechanical properties. They show great promise in various technological and biomedical applications, including tissue engineering, and bone and cartilage substitution. To evaluate the bioactivity of bone substitutes, researchers typically conduct in vitro tests using simulated body fluids and specific cell lines, while in vivo testing involves the study of materials in different animal species. In this context, our primary focus is to investigate the applications of different types of aerogels, considering their specific materials, microstructure, and porosity in the field of bone and cartilage tissue engineering. From clinically approved materials to experimental aerogels, we present a comprehensive list and summary of various aerogel building blocks and their biological activities. Additionally, we explore how the complexity of aerogel scaffolds influences their in vivo performance, ranging from simple single-component or hybrid aerogels to more intricate and organized structures. We also discuss commonly used formulation and drying methods in aerogel chemistry, including molding, freeze casting, supercritical foaming, freeze drying, subcritical, and supercritical drying techniques. These techniques play a crucial role in shaping aerogels for specific applications. Alongside the progress made, we acknowledge the challenges ahead and assess the near and far future of aerogel-based hard tissue engineering materials, as well as their potential connection with emerging healing techniques. Keywords: aerogel; tissue engineering; artificial bone substitution; in vitro and in vivo bioactivity; biodegradation; cartilage regeneration; scaffold; osteogenesis; simulated body fluids; immortalized cell lines 1. Introduction Bone is a rigid tissue with essential functions in providing structural support, pro- tecting vital organs, and enabling movement [1]. It consists of an organic matrix (20%), primarily made up of type I collagen, a mineral phase (65%) predominantly composed of hydroxyapatite [Ca 10 (PO 4 ) 6 (OH) 2 , HAp], water (10%), and various bioactive factors and cells, mainly osteoblasts and osteoclasts [2]. Bone has a natural regenerative process that is regulated by biomechanical, cellular, and molecular factors [3]. Articular cartilage is a thin layer covering the ends of bones, allowing smooth gliding and facilitating proper joint function. The cartilage tissue is a sturdy, flexible avascular structure composed of collagen, proteoglycan, non-collagenous proteins, and water. A unique feature of cartilage is its close connection with the underlying hard subchondral bone, comprising three distinct components: highly mineralized subchondral, intermediate-mineralized calcified, and non-mineralized tissues, separated by a dense tidemark. Gels 2023, 9, 746. https://doi.org/10.3390/gels9090746 https://www.mdpi.com/journal/gels