The development of programmable functional biomaterials makes 4D printing add a new dimension, time (t), based on 3D structures (x, y, z), therefore, 4D printed constructs could transform their morphology or function over time in response to environmental stimuli. Nowadays, highly efficient bone defect repair remains challenging in clinics. Combining programmable biomaterials, living cells, and bioactive factors, 4D bioprinting provides greater potential for constructing dynamic, personalized, and precise bone tissue engineering scaffolds by complex structure formation and functional maturation. Therefore, 4D bioprinting has been regarded as the next generation of bone repair technology. This review focuses on 4D printing and its advantages in orthopedics. The applications of different smart biomaterials and 4D printing strategies are briefly introduced. Furthermore, one summarizes the recent advancements of 4D printing in bone tissue engineering, uncovering the addressed and unaddressed medical requirements. In addition, current challenges and future perspectives are further discussed, which will offer more inspiration about the clinical transformation of this emerging 4D bioprinting technology in bone regeneration.

Harnessing 4D Printing Bioscaffolds for Advanced Orthopedics.

Extracellular vesicles (EVs) are a collective term for nanoscale or microscale vesicles secreted by cells that play important biological roles. Mesenchymal stem cells are a class of cells with the potential for self-healing and multidirectional differentiation. In recent years, numerous studies have shown that EVs, especially those secreted by mesenchymal stem cells, can promote the repair and regeneration of various tissues and, thus, have significant potential in regenerative medicine. However, due to the rapid clearance capacity of the circulatory system, EVs are barely able to act persistently at specific sites for repair of target tissues. Hydrogels have good biocompatibility and loose and porous structural properties that allow them to serve as EV carriers, thereby prolonging the retention in certain specific areas and slowing the release of EVs. When EVs are needed to function at specific sites, the EV-loaded hydrogels can stand as an excellent approach. In this review, we first introduce the sources, roles, and extraction and characterization methods of EVs and describe their current application status. We then review the different types of hydrogels and discuss factors influencing their abilities to carry and release EVs. We summarize several strategies for loading EVs into hydrogels and characterizing EV-loaded hydrogels. Furthermore, we discuss application strategies for EV-loaded hydrogels and review their specific applications in tissue regeneration and repair. This article concludes with a summary of the current state of research on EV-loaded hydrogels and an outlook on future research directions, which we hope will provide promising ideas for researchers. 

https://doi.org/10.1016/j.mtbio.2022.100522

Extracellular vesicle-loaded hydrogels for tissue repair and regeneration

Articular cartilage lesions resulting from injurious impact, recurring loading, joint malalignment, etc., are very common and encompass the risk of evolving to serious cartilage diseases such as osteoarthritis. To date, cartilage injuries are typically treated via operative procedures such as autologous chondrocyte implantation (ACI), matrix-associated autologous chondrocyte implantation (MACI) and microfracture, which are characterized by low patient compliance. Accordingly, cartilage tissue engineering (CTE) has received a lot of interest. Cell-laden hydrogels are favorable candidates for cartilage repair since they resemble the native tissue environment and promote the formation of extracellular matrix. Various types of hydrogels have been developed so far for CTE applications based on both natural and synthetic biomaterials. Among these materials, hyaluronic acid (HA), a principal component of the cartilage tissue which can be easily modified and biofunctionalized, has been favored for the development of hydrogels since it interacts with cell surface receptors, supports the growth of chondrocytes and promotes the differentiation of mesenchymal stem cells to chondrocytes. The present work reviews the various types of HA-based hydrogels (e.g., in situ forming hydrogels, cryogels, microgels and three-dimensional (3D)-bioprinted hydrogel constructs) that have been used for cartilage repair, specially focusing on the results of their preclinical and clinical assessment.

https://www.mdpi.com/2073-4360/14/4/839/pdf?version=1645612198

Recent Developments in Hyaluronic Acid-Based Hydrogels for Cartilage Tissue Engineering Applications

Highly Stretchable, Tough, and Conductive Ag@Cu Nanocomposite Hydrogels for Flexible Wearable Sensors and Bionic Electronic Skins

Tissue and organ failure has induced immense economic and healthcare concerns across the world. Tissue engineering is an interdisciplinary biomedical approach which aims to address the issues intrinsic to organ donation by providing an alternative strategy to tissue and organ transplantation. This review is specifically focused on cartilage tissue. Cartilage defects cannot readily regenerate, and thus research into tissue engineering approaches is relevant as a potential treatment option. Cells, scaffolds, and growth factors are three components that can be utilized to regenerate new tissue, and in particular recent advances in microparticle technology have excellent potential to revolutionize cartilage tissue regeneration. First, microspheres can be used for drug delivery by injecting them into the cartilage tissue or joint space to reduce pain and stimulate regeneration. They can also be used as controlled release systems within tissue engineering constructs. Additionally, microcarriers can act as a surface for stem cells or chondrocytes to adhere to and expand, generating large amounts of cells, which are necessary for clinically relevant cell therapies. Finally, a newer application of microparticles is to form them together into granular hydrogels to act as scaffolds for tissue engineering or to use in bioprinting. Tissue engineering has the potential to revolutionize the space of cartilage regeneration, but additional research is needed to allow for clinical translation. Microparticles are a key enabling technology in this regard.

/pdf/a-review-of-the-use-of-microparticles-for-cartilage-tissue-1tapygphvn.pdf

A Review of the Use of Microparticles for Cartilage Tissue Engineering.

Cartilage regeneration and repair remain a clinical challenge due to the limited capability of cartilage to self-regenerate. Worldwide, the costs associated with cartilage regeneration per patient are estimated on average £30 000 for producing and supplying cells. Regenerative approaches may include the use of cell therapies and tissue engineering by combining relevant cells, scaffolds and instructive biomolecules to stimulate or modulate cartilage repair. Hydrogels have been of great interest within these fields to be used as 3D substrates to cultivate and grow cartilage cells. Currently, biomimetic hydrogels with adequate biological and physicochemical properties, such as mechanical properties, capable of supporting load-bearing capability, are yet to succeed. In this review, biomaterials’ advantages and disadvantages for the manufacturing of biomimetic hydrogels for cartilage regeneration are presented. Different studies on the formulation of cartilage-like hydrogels based on materials such as gelatin, chondroitin sulfate, hyaluronic acid and polyethylene glycol are summarised and contrasted in terms of their mechanical properties (e.g. elastic modulus) and ability to enhance cell function such as cell viability and GAG content. Current limitations and challenges of biomimetic hydrogels for cartilage regeneration are also presented.

/pdf/biomimetic-hydrogels-designed-for-cartilage-tissue-3l3h2xfzyo.pdf

Kresanti D Ngadimin

Papers

Biomimetic hydrogels designed for cartilage tissue engineering