Recent Progress in Hydrogel-Based Synthetic Cartilage: Focus on Lubrication and Load-Bearing Capacities

Abstract

Articular cartilage (AC), which covers the ends of bones in joints, particularly the knee joints, provides a robust interface to maintain frictionless movement during daily life due to its remarkable lubricating and load-bearing capacities. However, osteoarthritis (OA), characterized by the progressive degradation of AC, compromises the properties of AC and thus leads to frayed and rough interfaces between the bones, which subsequently accelerates the progression of OA. Hydrogels, composed of highly hydrated and interconnected polymer chains, are potential candidates for AC replacement due to their physical and chemical properties being similar to those of AC. In this review, we summarize the recent progress of hydrogel-based synthetic cartilage, or cartilage-like hydrogels, with a particular focus on their lubrication and load-bearing properties. The different formulations, current limitations, and challenges of such hydrogels are also discussed. Moreover, we discuss the future directions of hydrogel-based synthetic cartilage to repair and even regenerate the damaged AC.

Keywords: articular cartilage; hydrogels; implants; load-bearing; lubrication.

Figure 1

Illustration of the components and structure of AC. (A) The knee synovial joint is mainly composed of the synovial membrane, AC, and the synovial fluid within the synovial cavity. (B) AC is characterized by its layered structure. Chondrocytes make up less than 5% (volume fraction) of AC. The main composition of ECM, type II collagen, glycosaminoglycans, collagen X, and the depth-dependent modulus, are indicated. (C) Illustration of the outer surface of AC that determines the lubrication performance of AC. Glycosaminoglycans, including hyaluronic acid (HA) and aggrecan, as well as lubricin and phospholipids (are not shown here) synergically assemble to form a lubrication layer outer of the AC surface to determine its remarkable lubrication at high pressure. Reprinted with permission from Ref [4]. Copyright 2021, Wiley-VCH.

Figure 2

Schematic illustration of ICRS classification system of AC defects (A) and schematic diagram of traditionally used clinical repair strategies and hydrogel-based AC tissue engineering for AC defects (B). Reprinted with permission from Ref [28]. Copyright 2022, Elsevier.

Figure 3

Synthetic hydrogel composites with mechanical strength comparable to or even greater than AC. (A) Illustration of the BC–PVA–PAMPS hydrogel fabrication process. Reprinted with permission from Ref [62]. Copyright 2020, Wiley-VCH. (B) Compressive strength and compressive modulus of annealed BC–PVA–PAMPS hydrogel (mean ± SD), and the friction coefficient of annealed BC–PVA–PAMPS hydrogels sliding against AC. (C) Illustration of treatment of AC defect using annealed BC–PVA–PAMPS hydrogel. Panels (B,C) are reprinted with permission from Ref [63]. Copyright 2022, Wiley-VCH.

Figure 4

Phospholipid-inspired cartilage-like hydrogels. (A) Illustration of the self-lubricating and lipid-incorporated hydrogel. The incorporated lipids formed micro-reservoirs throughout the gel bulk, and additional micro-reservoirs were exposed due to friction, which enabled the boundary lubrication layer of the lipids to form on the surface, leading to a reduction in friction via hydration lubrication. Reprinted with permission from Ref [67]. Copyright 2022, Elsevier. (B) Schematic illustrating of the formation PMS-HSPC(SUV)-HA hydrogel and the synergistic lubrication mechanism. The super-lubricated state after the incorporation of lipid SUV and HA was mainly attributed to the synergistic lubrication effect between lipids and HA after the formation of uniformly arranged lipid liposomes around the HA structure. Reprinted with permission from Ref [65]. Copyright 2022, Elsevier. (C) Schematic illustration of the synthesis of lipid-lubricated hydrogels with biocompatible, high-strength lipid-lubrication performance. Reprinted with permission from Ref [66]. Copyright 2022, Elsevier.

Figure 5

Typical cartilage structure-inspired hydrogels. (A) The main components consisted of an AC lubrication system within the AC superficial layer (left). The SEM cross-sectional morphology of Composite-LP, which clearly shows the load-bearing phase and lubrication phase (right). (B) The friction coefficients of the Composite-LP, Hg-LP, Composite, and Hg samples (load, 1 N; frequency, 1 Hz). Panels (A,B) are reprinted with permission from Ref [25]. Copyright 2022, American Chemical Society. (C) Schematic illustration of the bilayer-oriented heterogeneous hydrogel (BH-CF/MMT hydrogel). (D) The compressive strength and compressive modulus (D) and the average friction coefficient (E) of the bilayer-oriented heterogeneous hydrogel compared with control groups (bilayer unoriented hydrogel, A-MMT hydrogel, and A-MMT hydrogel). Reprinted with permission from Ref [70]. Copyright 2022, American Chemical Society.

Figure 6

Preparation of cartilage components (proteoglycans and lubricin) and layer structure-inspired “CS” and layer “CS-Fe” hydrogels and their main functions, including mechanical adaptability, low friction, and inflammation regulation. Reprinted with permission from Ref [71]. Copyright 2022, American Chemical Society.

Figure 7

(A) Steps in the synthesis of POx/PAA double-network hydrogels. (B) Compressive strength and failure load of AC and POx/PAA hydrogels in PBS (pH 7.4). (C) The friction coefficient of POx/PAA hydrogels lubricated by PBS (pH 7.4) and egg white. Reprinted with permission from Ref [75]. Copyright 2022, John Wiley and Sons.

Figure 8

(A) Schematic illustration of the fabrication procedures of TEHy-x via the swelling-freeze–thaw method. (B) Compressive toughness and compressive strength of TEHy-x under different numbers of FTS cycles. (C) Static and sliding friction coefficients of TEHy-6 under different loads. (D) Summary and comparison of seven properties of the TEHy-x and AC in a radar chart. Reprinted with permission from Ref [82]. Copyright 2022, American Chemical Society.