Swell gel - anisotropic hydrogel systems for surgical tissue expansion

Materials World magazine
,
3 Sep 2010
A partially inflated rectangular balloon tissue expander filled with saline solution (containing methylene blue dye). The filling port is highlighted by the red arrow.

Anisotropic hydrogel systems for surgical tissue expansion have been developed to aid soft tissue growth. Dr Jinhyun Hannah Lee, Post-doctoral Research Fellow at the University of Oxford, UK, reports on the process.

A tissue expander is an implantable surgical device used to create additional soft tissue. It can be used to reconstruct a wide variety of skin defects. These include congenital anomalies, such as cleft palate, anophthalmia (absent eye) and syndactyly (webbed fingers and toes), traumatic defects (resulting from burns or road traffic accidents) or following cancer surgery, such as breast reconstruction. The research team at the University of Oxford, UK, has developed a hydrogel system that is capable of controlled anisotropic swelling over a pre-determined period. This enables the expander technology to be applied to a range of complex reconstructive situations for which no device was previously suitable.

Balloon trip

The first reported clinical application of this technique was in 1957 when a rubber catheter balloon was surgically implanted behind a partially avulsed ear. Additional skin was created in order to reconstruct the ear by gradually inflating the balloon with air. This device was later extensively modified by using a silicone balloon that is inflated by an implantable filling port. These expanders have been in regular clinical use for over 30 years, however, their use in certain applications is limited by their bulky size, isotropic expansion and need for percutaneous inflation, which can be painful and is poorly tolerated by children.

The concept of a self-inflating tissue expander, capable of independent osmotically driven swelling, was introduced in the early 1980s. Comprising a semi-permeable silicone membrane, filled with hypertonic saline solution, this device was successfully used in a number of soft tissue reconstructions. Although the degree of potential swelling is limited, a significant risk of soft tissue necrosis exists in the event of silicone shell rupture.

A new generation of self-inflating expanders was developed in the 1990s based on hydrogels composed of copolymers of vinyl-2-pyrrolidinone (VP) and either methyl methacrylate (MMA) or poly(hydroxyethyl methacrylate) (HEMA).

Hydrogels are widely used as medical devices due to their biocompatibility, similar physical properties to human tissue, and controllable swelling and mechanical properties. Hydrogel expanders are usually deployed in the anhydrous (xerogel) state. Once implanted within a surgically created subcutaneous pocket, the devices absorb local tissue fluid by osmosis and gradually increase in size. On stretching the overlying skin, a complex biological cascade is initiated that ultimately results in de novo soft tissue. Isotropic VP/MMA hydrogels have been commercialised and are in regular clinical use for a variety of reconstruction indications, although their unsophisticated swelling capabilities limit clinical efficacy.

Meeting needs

A key requirement of hydrogel expander systems is that they are entirely biocompatible and can be sterilised – by gamma irradiation or by steam autoclave – prior to surgical implantation. Expander devices must have a high swelling capacity with a gradual, controllable, swelling rate. Mechanical integrity needs to be maintained throughout swelling and gel functionality could be significantly extended by introducing an anisotropic expansion profile.

Crucially, either varying the polymer type or modulating the hydrogel’s morphology, which can also affect its mechanical integrity, can control swelling behaviour. Once surgically implanted, the hydrophilic hydrogels continue to swell until an equilibrium is obtained between the driving force created by their interaction with the solvent (water) molecules and the restoring force caused by the polymer network’s elasticity. When these forces are balanced, the swelling is saturated.

Consequently, by subtly altering the chemical species within the gel, as well as the network structure, it is possible to precisely develop a hydrogel with the appropriate properties.

Clinically desirable swelling kinetics comprise three phases. The first phase is the ‘lag period’, whereby the onset of gel swelling is delayed by approximately two weeks following implantation in order to allow partial wound healing, minimising the risk of wound dehiscence and subsequent device extrusion. This delay is obtained by temporarily restricting water diffusion into the gels by either manipulating the hydrogel’s morphology or components, or by coating the system with a hydrophobic species.

The next phase is the period of controlled gel swelling from the xerogel to fully swollen hydrogel state. Gradual swelling is essential in order to minimise the risk of tissue ischaemia and possible skin necrosis. It should ideally occur over a period of two to four months, and is controlled either by adjusting the network structure and its components, or by coating the xerogel with rubber membranes that are capable of reducing the water diffusion into the system.

The final phase is the equilibrium period, whereby the hydrogel has reached its maximal degree of swelling and remains in a structurally stable state until the patient is scheduled for their final operative procedure where the device is removed and the additional expanded skin is used to reconstruct the defect in question. Maximal hydrogel swelling is governed by factors including the type and quantity of hydrophilic functional groups, such as -COOH, >C=O, >COH, or –NH2, within the system, and the larger mesh size of the network, determined by the gel’s smaller crosslinking density. Caution must be exercised as decreasing the crosslinking density reduces the mechanical integrity of the gel.

For repairing anatomical defects that have a degree of anatomical directionality, such as a palate, digit, lower eyelid or dorsal nasal bridge, it is desirable to use a device capable of anisotropic swelling, as this should limit the risk of device extrusion. Annealing and compressing the isotropic xerogel at a temperature near the glass transition temperature (Tg) for a specified period of time, prepares the anisotropic gels. The reconfigured gel is allowed to cool in order to fix polymer chain alignment within the gel network.

Subsequent anisotropic swelling occurs in the direction opposite to the applied direction of compressive force and is thought to be caused by unfurling of the folded chains due to the gel’s shape memory nature, and by the chains’ isotropic swelling due to osmotic pressure. The degree of compression dictates the degree of gel anisotropy, which finally affects the level of swelling in the controlled direction.

Above, left: Desirable swelling kinetics of an ideal hydrogel tissue expander. Above, right: The schematics of the compressed gel (upper left) and its fully swollen hydrogel (upper right), and their expected corresponding confirmations of the polymer chains between crosslinking junctions at the molecular level

 

Further information

Dr Jinhyun Hannah Lee, Department of Materials, University of Oxford, Parks Road, Oxford, OX1 3PH, UK. Tel: +44 (0) 1865 273714. Email: hannah.lee@materials.ox.ac.uk

Thanks to co-authors Marc Christopher Swan, Specialist Registrar in Plastic and Reconstructive Surgery at John Radcliffe Hospital, Oxford, UK and Dr Jan T Czernuszka, Lecturer at the Department of Materials, University of Oxford. Also see Hydrogel fix for cleft palate (Materials World, May 2010, p12).