Hydrogel delivery systems can leverage therapeutically beneficial outcomes of drug delivery and have found clinical use. Hydrogels can provide spatial and temporal control over the release of various therapeutic agents, including small-molecule drugs, macromolecular drugs and cells. Owing to their tunable physical properties, controllable degradability and capability to protect labile drugs from degradation, hydrogels serve as a platform in which various physiochemical interactions with the encapsulated drugs control their release. In this Review, we cover multiscale mechanisms underlying the design of hydrogel drug delivery systems, focusing on physical and chemical properties of the hydrogel network and the hydrogel-drug interactions across the network, mesh, and molecular (or atomistic) scales. We discuss how different mechanisms interact and can be integrated to exert fine control in time and space over the drug presentation. We also collect experimental release data from the literature, review clinical translation to date of these systems, and present quantitative comparisons between different systems to provide guidelines for the rational design of hydrogel delivery systems.

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Designing hydrogels for controlled drug delivery.

http://pubs.acs.org/doi/pdf/10.1021/bm060620d

The future prospects of microbial cellulose in biomedical applications.

https://pure.hw.ac.uk/ws/files/10835033/final12Oct_11024_Melchels_et_al_Additive_Manufacturing_of_Tissues_and_Organs_R1_1_.pdf

Additive manufacturing of tissues and organs

As swollen polymer networks in water, hydrogels are usually brittle. However, hydrogels with high toughness play critical roles in many plant and animal tissues as well as in diverse engineering applications. Here we review the intrinsic mechanisms of a wide variety of tough hydrogels developed over the past few decades. We show that tough hydrogels generally possess mechanisms to dissipate substantial mechanical energy but still maintain high elasticity under deformation. The integrations and interactions of different mechanisms for dissipating energy and maintaining elasticity are essential to the design of tough hydrogels. A matrix that combines various mechanisms is constructed for the first time to guide the design of next-generation tough hydrogels. We further highlight that a particularly promising strategy for the design is to implement multiple mechanisms across multiple length scales into nano-, micro-, meso-, and macro-structures of hydrogels.

Multi-scale multi-mechanism design of tough hydrogels: building dissipation into stretchy networks

Additive manufacturing techniques offer the potential to fabricate organized tissue constructs to repair or replace damaged or diseased human tissues and organs. Using these techniques, spatial variations of cells along multiple axes with high geometric complexity in combination with different biomaterials can be generated. The level of control offered by these computer-controlled technologies to design and fabricate tissues will accelerate our understanding of the governing factors of tissue formation and function. Moreover, it will provide a valuable tool to study the effect of anatomy on graft performance. In this review, we discuss the rationale for engineering tissues and organs by combining computer-aided design with additive manufacturing technologies that encompass the simultaneous deposition of cells and materials. Current strategies are presented, particularly with respect to limitations due to the lack of suitable polymers, and requirements to move the current concepts to practical application.

Biomechanical properties of high-toughness double network hydrogels.

This study evaluated the in vivo influence of a poly-(2-Acrylamido-2-methylpropane sulfonic acid)/poly-(N,N'-dimetyl acrylamide) (PAMPS/PDMAAm) double-network (DN) hydrogel on counterface cartilage in rabbit knee joints and its ex vivo friction properties on normal cartilage. In the first experiment, the DN gel was implanted in a surgically created defect in the femoral trochlea of rabbit knee joints and the left knee was used as the control. Evaluations using a confocal laser scanning microscopy demonstrated that the DN gel did not affect the surface microstructure (surface roughness, the number of small pits) of the counterface cartilage in vivo at 4 and 12 weeks. The histology also showed that the DN gel hadno pathological damage on the cartilage matrices and cells at 4 weeks. However, two of the five DN gel-implanted knees showed mild irregularity on the counterface cartilage surface at 12 weeks. In the second experiment, the friction property between the normal and the artificial cartilage was determined using a joint simulator apparatus. The ex vivo mean friction coefficient of the DN gel to normal cartilage was 0.029, while that of the normal-to-normal cartilage articulation was 0.188. The coefficient of the DN gel-to-normal cartilage articulation was significantly lower than that of the normal-to-normal cartilage articulation (p < 0.0001). This study suggested that the PAMPS/PDMAAm DN gel has very low friction coefficient on normal cartilage and has no significant detrimental effects on counterface cartilage in vivo, and can be a promising material to develop the artificial cartilage.

Artificial cartilage made from a novel double-network hydrogel: In vivo effects on the normal cartilage and ex vivo evaluation of the friction property.

The present study aimed to determine the effect of femoral component materials and sterilization methods on wear properties of total knee prostheses by using a knee simulator test and retrieval analysis. The simulator test revealed that ultrahigh molecular weight polyethylene (UHMWPE) inserts had remarkably lower wear against the ceramic femoral component than against the Co-Cr femoral component. However, the retrieval study revealed no significant difference in the linear wear between the former and the latter. The alumina ceramic/UHMWPE insert combination showed a mild wear. However, whether cross-linking by gamma-ray sterilization reduces wear remained unconfirmed. In contrast, oxidative degradation and/or delamination was confirmed. Thus, we conclude that alumina ceramic/ethylene oxide gas–sterilized UHMWPE insert in a total knee prosthesis might exhibit a good wear resistance.

Ceramic Versus Cobalt-Chrome Femoral Components; Wear of Polyethylene Insert in Total Knee Prosthesis

The wear characteristics of ultra-high-molecular-weight polyethylene acetabular cups irradiated with 6.0 to 7.5 Gy of gamma-irradiation were studied in a hip simulator and in vivo in 70 hips for 6 to 39 months. The linear wear was 2.5% to 4.5% of the wear seen in conventional polyethylene cups. A biphasic wear pattern was observed over time with a relatively large wear in the first year and a subsequent leveling of the wear rate curve. The linear wear rate in the second phase (steady state) was 0.006 mm/y. The extent of decrease in clinical wear of 6.0-Mrad polyethylene (Aeonian, Kyocera Corp, Kyoto, Japan) cups is comparable with the decrease of the in vitro wear measured by the hip simulation test.

Wear of Highly Cross-linked Polyethylene Acetabular Cup in Japan

We investigated articular bearing surfaces retrieved from three patients with ceramic-on-ceramic total hip arthroplasties using high-quality alumina. The duration of implantation was 3.5, 3.0, and 2.5 years, respectively. Dislocation of the hip joint after implantation did not occur in any patients. The retrieved prostheses were examined by stereomicroscopy and scanning electron microscopy (SEM). In the main load-bearing area, no wear marks were seen in any sockets. However, in all three cases, stripe scars were observed at the rim of the alumina inlay under stereomicroscopy, despite the lack of indentation in the socket and the stem, which suggests impingement. Such scars were not observed on the load-bearing surface. Under SEM, the scars showed excessive wear, including material excavation, that has not been observed in conventional hip simulator experiments. These findings are similar to those of experiments in which a simulator was programmed to distract the femoral head from the socket. The present results suggest that the femoral head can separate from the socket without neck-socket impingement in vivo.

Wear analysis of retrieved ceramic-on-ceramic articulations in total hip arthroplasty: Femoral head makes contact with the rim of the socket outside of the bearing surface.

Masaru Ueno

Papers

Biomechanical properties of high-toughness double network hydrogels.

Artificial cartilage made from a novel double-network hydrogel: In vivo effects on the normal cartilage and ex vivo evaluation of the friction property.

Ceramic Versus Cobalt-Chrome Femoral Components; Wear of Polyethylene Insert in Total Knee Prosthesis

Wear of Highly Cross-linked Polyethylene Acetabular Cup in Japan

Wear analysis of retrieved ceramic-on-ceramic articulations in total hip arthroplasty: Femoral head makes contact with the rim of the socket outside of the bearing surface.