Regenerative medicine has been attracting tremendous attention during the past few decades because it is promising in overcoming the limitations of donor shortage and immune complications in direct transplantations. The ongoing progress in this field calls for the rapid growth of living materials, which consist of live biological agents and can be designed together with synthetic materials to meet the application demands of regenerative medicine. In this review, we present a summary of the state-of-the-art progress of living materials that are applied in regenerative medicine. We first introduce the advanced engineering approaches that are employed to prepare living materials containing live cells, typically including genetic engineering, cell coating, microfluidics, and bioprinting, etc. Afterwards, we enumerate different application aspects of living materials in regenerative medicine, including tissue scaffold, cell therapy, tissue models, and so on. Finally, we give a concise conclusion and provide a perspective of this field.

Living Materials for Regenerative Medicine

3D bioprinting technology can rapidly process cell-loaded biomaterials to prepare personalized scaffolds for repairing defective tissues, tissue regeneration, and even printing tissues or organs. 3D bioprinting relies on bioinks with appropriate rheology and cytocompatibility, and hydrogels are among the most promising bioink materials for 3D bioprinting. Among many hydrogel precursor materials, hyaluronic acid (HA) stands out due to its excellent physicochemical and biological properties, such as biocompatibility, hydrophilicity, non-immunogenicity, and complete biodegradability, and has become the most attractive hydrogel precursor for bioinks. In this review, we discuss the strategies adopted for the application of HA-based hydrogels as bioinks, including printability, improving their mechanical properties, and printing with loaded cells. Finally, we summarize the application of 3D bioprinted HA-based hydrogels in various tissue engineering applications in recent years, with the aim to provide fresh inspiration for further development of HA-based hydrogels for 3D bioprinting. 

Recent advances in hyaluronic acid-based hydrogels for 3D bioprinting in tissue engineering applications

Tissue engineering is a promising strategy for damaged cartilage tissue repair. Three-dimensional (3D) printed hydrogel exhibits great potential in cartilage tissue engineering for fabricating 3D cell culture scaffolds, owing to its similarity to the extracellular matrix (ECM). Numerous hydrogels have been tested for 3D printing in vitro articular cartilage tissues, including natural and synthetic hydrogels that mimic their in vivo counterparts. The advancement of materials science and 3D printing techniques enables a wide range of fabrication strategies that produce cartilage tissues with delicate structures and on multiple scales. Stimuli-responsive hydrogels, which rely on the external environment to transform to a desired structure or dimension, have likewise been widely studied in tissue engineering. This review summarizes the characteristics, functions, and research conducted on 3D printed hydrogels by categorizing cutting-edge hydrogel materials commonly used in cartilage tissue engineering and their complexes. The challenges and application prospects of hydrogels in cartilage tissue engineering are described. Novel composite hydrogels must be investigated to meet the requirements of native articular cartilage in the aspects of structure, scale, mechanical properties, among others. Combining stimuli-responsive hydrogels with biological scaffolds also shows great potential in various applications, including but not limited to articular cartilage, vascularization, and osteochondral repair. 

3D printed hydrogel for articular cartilage regeneration

Shedding light on 3D printing: Printing photo-crosslinkable constructs for tissue engineering.

In the human body, articular cartilage facilitates the frictionless movement of synovial joints. However, due to its avascular and aneural nature, it has a limited ability to self-repair when damaged due to injury or wear and tear over time. Current surgical treatment options for cartilage defects often lead to the formation of fibrous, non-durable tissue and thus a new solution is required. Nature is the best innovator and so recent advances in the field of tissue engineering have aimed to recreate the microenvironment of native articular cartilage using biomaterial scaffolds. However, the inability to mirror the complexity of native tissue has hindered the clinical translation of many products thus far. Fortunately, the advent of 3D printing has provided a potential solution. 3D printed scaffolds, fabricated using biomimetic biomaterials, can be designed to mimic the complex zonal architecture and composition of articular cartilage. The bioinks used to fabricate these scaffolds can also be further functionalised with cells and/or bioactive factors or gene therapeutics to mirror the cellular composition of the native tissue. Thus, this review investigates how the architecture and composition of native articular cartilage is inspiring the design of biomimetic bioinks for 3D printing of scaffolds for cartilage repair. Subsequently, we discuss how these 3D printed scaffolds can be further functionalised with cells and bioactive factors, as well as looking at future prospects in this field.

Articulation inspired by nature: a review of biomimetic and biologically active 3D printed scaffolds for cartilage tissue engineering

Three-dimensional (3D) bioprinting has become a promising strategy for bone manufacturing, with excellent control over geometry and microarchitectures of the scaffolds. The bioprinting ink for bone and cartilage engineering has thus become the key to developing 3D constructs for bone and cartilage defect repair. Maintaining the balance of cellular viability, drugs or cytokines' function, and mechanical integrity is critical for constructing 3D bone and/or cartilage scaffolds. Photo-crosslinkable hydrogel is one of the most promising materials in tissue engineering; it can respond to light and induce structural or morphological transition. The biocompatibility, easy fabrication, as well as controllable mechanical and degradation properties of photo-crosslinkable hydrogel can meet various requirements of the bone and cartilage scaffolds, which enable it to serve as an effective bio-ink for 3D bioprinting. Here, in this review, we first introduce commonly used photo-crosslinkable hydrogel materials and additives (such as nanomaterials, functional cells, and drugs/cytokine), and then discuss the applications of the 3D bioprinted photo-crosslinkable hydrogel scaffolds for bone and cartilage engineering. Finally, we conclude the review with future perspectives about the development of 3D bioprinting photo-crosslinkable hydrogels in bone and cartilage engineering.

http://ijb.whioce.com/index.php/int-j-bioprinting/article/viewFile/367/pdf

Yaxiong Liu

Papers

3D Bioprinting Photo-Crosslinkable Hydrogels for Bone and Cartilage Repair