Hydrogels, due to their unique biocompatibility, flexible methods of synthesis, range of constituents, and desirable physical characteristics, have been the material of choice for many applications in regenerative medicine. They can serve as scaffolds that provide structural integrity to tissue constructs, control drug and protein delivery to tissues and cultures, and serve as adhesives or barriers between tissue and material surfaces. In this work, the properties of hydrogels that are important for tissue engineering applications and the inherent material design constraints and challenges are discussed. Recent research involving several different hydrogels polymerized from a variety of synthetic and natural monomers using typical and novel synthetic methods are highlighted. Finally, special attention is given to the microfabrication techniques that are currently resulting in important advances in the field.

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Hydrogels in regenerative medicine

Photopolymerizable hydrogels for tissue engineering applications.

Scaffolds for tissue fabrication

Photoinitiated polymerization of PEG-diacrylate with lithium phenyl-2,4,6-trimethylbenzoylphosphinate: polymerization rate and cytocompatibility.

This paper reviews recent work involving polymeric biomaterials used for skin, cartilage, bone, vascular, nerve and liver regeneration. Skin trauma involves damage to the epidermal, dermal and/or subdermal tissues. Epithelial, dermal and full-thickness replacements are considered. Cartilage research is mainly focused on replacing hyaline cartilage. Researchers investigate both nondegradable polymers, which must provide mechanical stability, and degradable polymers, which must support cartilage regeneration. Natural healing in large bone defects often fails. Materials for bone reconstruction must be biocompatible, offer mechanical properties similar to those of bone and support tissue regeneration. The area of vascular grafts draws attention as improvements to the patency of existing materials are needed. Studies to improve current vascular graft polymers as well as develop new polymers are reviewed below. The design and testing of materials for nerve regeneration, to repair damage caused by illness or accident, is an active area of research. Directional nerve guidance via tubulation is discussed, as are matrix materials to enhance axonal extension. Finally, liver transplantation remains one of the only options for chronic liver disease and the demand for liver transplants far exceeds the number of available organs. The complexity of parameters involved in liver regeneration is presented here.

Polymeric biomaterials for tissue and organ regeneration

Transdermal photopolymerization, a minimally invasive method for implantation, was used to subcutaneously place a mixture of polymer and isolated chondrocytes to regenerate cartilage tissue in vivo. Semi-interpenetrating networks of varying proportions of poly(ethylene oxide)-dimethacrylate and poly(ethylene oxide) and primary bovine articular chondrocytes were implanted in athymic mice. Four mice (12 implants) were harvested at 2, 4, and 7 weeks. Chondrocytes survived implantation and photopolymerization and formed neocartilage containing 1.5 to 2.9% wet weight collagen and 4 to 7% glycosaminoglycan. Thirty-five percent of the total collagen was type II collagen. Histologic analysis exhibited tissue structure resembling neocartilage, and safranin O staining demonstrated glycosaminoglycan distribution throughout the hydrogels. This study demonstrates the potential use of transdermal photopolymerization for minimally invasive subcutaneous implantation of hydrogels and chondrocytes for in vivo cartilage regeneration.

Transdermal photopolymerization of poly(ethylene oxide)-based injectable hydrogels for tissue-engineered cartilage.

Compositions for tissue engineering and drug delivery have been developed based on solutions of two or more polymers which form semi-interpenetrating or interpenetrating polymer networks upon exposure to active species following injection at a site in a patient in need thereof. The polymers crosslink to themselves but not to each other; semi-interpenetrating networks are formed when only one of the polymers crosslink. The resulting viscous solutions retain the biologically active molecules or cells at the site of injection until release or tissue formation, respectfully, occurs. As a result of studies conducted with polymer-cell suspensions forming interpenetrating polymer networks, it has been determined that polymer solutions can be formulated wherein the active species is provided by exposure of the polymer solution to an exogenous source of active species, typically electromagnetic radiation, preferably light. Studies demonstrate that light will penetrate through skin, body fluids (such as synovial fluid) and membranes and polymerize the polymer solutions. The polymer solutions can be crosslinked ionically or covalently, to form a hydrogel, semi-interpenetrating polymer network or an interpenetrating polymer network.

Derek Sims

Papers

Transdermal photopolymerization of poly(ethylene oxide)-based injectable hydrogels for tissue-engineered cartilage.

Semi-interpenetrating or interpenetrating polymer networks for drug delivery and tissue engineering