ReviewBiodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering
Introduction
Tissue engineering applies methods from materials engineering and life sciences to create artificial constructs for regeneration of new tissue [1]. One common approach is to isolate specific cells through a small biopsy from a patient to grow them on a three-dimensional (3D) scaffold under controlled culture conditions. Subsequently, the construct is delivered to the desired site in the patient's body with the aim to direct new tissue formation into the scaffold that can be degraded over time [1], [2], [3]. An alternative approach is to implant scaffolds for tissue ingrowth directly in vivo with the purpose to stimulate and to direct tissue formation in situ [2], [4], [5]. The advantage of this approach is the reduced number of operations needed, resulting in a shorter recovery time for the patient.
Facing a complex biological and sensitive system as the human body, the requirements of scaffold materials for tissue engineering are manifold and extremely challenging. First, biocompatibility of the substrate materials is imperative; that is the material must not elicit an unresolved inflammatory response nor demonstrate immunogenicity or cytotoxicity. In addition, the mechanical properties of the scaffold must be sufficient and not collapse during handling and during the patient's normal activities. As with all materials in contact with the human body, tissue scaffolds must be easily sterilizable to prevent infection [6]. This applies notably for bulk degradable scaffolds, where both the surface and the bulk material must be sterile. A further requirement for a scaffold particularly in bone engineering is a controllable interconnected porosity to direct the cells to grow into the desired physical form and to support vascularization of the ingrown tissue. A typical porosity of 90% as well as a pore diameter of at least 100 μm is known to be compulsory for cell penetration and a proper vascularization of the ingrown tissue [7], [8], [9], [10]. Other highly desirable features concerning the scaffold processing are near-net-shape fabrication and scalability for cost-effective industrial production.
Today, materials used for scaffolds are natural or synthetic polymers such as polysaccharides, poly(α-hydroxy ester), hydrogels or thermoplastic elastomers [2], [4], [11], [12]. Other important categories of materials are bioactive ceramics such as calcium phosphates and bioactive glasses or glass-ceramics [8], [13], [14]. Currently, composites of polymers and ceramics are being developed with the aim to increase the mechanical scaffold stability and to improve tissue interaction [14], [15], [16], [17], [18], [19]. In addition, efforts have also been invested in developing scaffolds with a drug-delivery capacity. These scaffolds can locally release growth factors or antibiotics and enhance bone ingrowth to treat bone defects and even support wound healing [14], [20], [21], [22], [23].
Aforementioned requirements for scaffold materials are numerous. To fulfill as many requirements as possible, composite systems combining advantages of polymers and ceramics seem to be a promising choice, in particular for bone tissue engineering, as demonstrated by the increasing research efforts worldwide [2], [14], [15], [16], [17], [18], [19], [20], [21], [22], [24], [25], [26], [27], [28], [29]. This paper reviews tissue engineering relevant biodegradable polymers and bioactive ceramics, including strategies for fabrication of composite scaffolds with interconnected pores. Microstructure and mechanical properties will be discussed and compared, evaluating open challenges in this field of biomedical materials research. In vitro and in vivo characteristics of porous composite scaffolds, with focus on bone regeneration, will be discussed as well as summarizing the currently available literature and pointing to research and development needs.
Section snippets
Biodegradable polymer matrices
There are two types of biodegradable polymers: The natural-based materials are one category, including polysaccharides (starch, alginate, chitin/chitosan, hyaluronic acid derivatives) or proteins (soy, collagen, fibrin gels, silk) and, as reinforcement, a variety of biofibers such as lignocellulosic natural fibers which are described in detailed studies and reviews elsewhere [30], [31], [32], [33], [34].
This review will focus on the second category, synthetic biodegradable polymers. Synthetic
Bioactive ceramic phases
A common characteristic of bioactive glasses and ceramics is a time-dependent kinetic modification of the surface that occurs upon implantation. The surface forms a biologically active hydroxy carbonate apatite (HCA) layer which provides the bonding interface with tissues. The HCA phase that forms on bioactive implants is chemically and structurally equivalent to the mineral phase in bone, providing interfacial bonding [13], [67]. The in vivo formation of an apatite layer on the surface of a
Material processing strategies for composite scaffolds with interconnected pores
Development of composite scaffold materials is attractive as advantageous properties of two or more types of materials can be combined to suit better the mechanical and physiological demands of the host tissue. By taking advantage of the formability of polymers and including controlled-volume fractions of a bioactive ceramic phase, mechanical reinforcement of the fabricated scaffold can be achieved [52], [125]. At the same time, the poor bioactivity of most polymers can be counteracted.
Probably
Mechanical integrity of porous scaffolds
Comparison of the mechanical properties of today's available porous scaffolds with relevant properties of bone reveals the insufficient mechanical integrity of the man-made scaffolds. In Fig. 3 the elastic modulus and the compressive strength of dense bioactive ceramic, biodegradable polymers, cancellous and cortical bone are compared with porous monophasic scaffolds and composites thereof. Mechanical data for porous bioactive ceramics and for polymer foams were taken from Refs. [105], [106],
Summary
The synthetic and biodegradable, polymer/inorganic bioactive phase composites reviewed in this article are particularly attractive as tissue engineering scaffolds due to their shapability, bioactive behavior and adjustable biodegradation kinetics. Conventional materials processing methods have been adapted and extended for incorporation of inorganic bioactive phases into porous and interconnected 3D polymer networks.
From the materials science perspective, the present challenge in tissue
Acknowledgment
Stimulating discussions with Prof. L.L. Hench, Prof. J. Polak and Dr. A. Bishop (TERM-Centre, Imperial College London) and with Dr. F. Filser (ETH Zurich) are acknowledged.
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