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Advanced Drug Delivery Reviews (v.59, #4-5)
Polymer carriers for drug delivery in tissue engineering
by Marina Sokolsky-Papkov; Kapil Agashi; Andrew Olaye; Kevin Shakesheff; Abraham J. Domb (pp. 187-206).
Growing demand for tissues and organs for transplantation and the inability to meet this need using by autogeneic (from the host) or allogeneic (from the same species) sources has led to the rapid development of tissue engineering as an alternative. Tissue engineering aims to replace or facilitate the regrowth of damaged or diseased tissue by applying a combination of biomaterials, cells and bioactive molecules. This review focuses on synthetic polymers that have been used for tissue growth scaffold fabrication and their applications in both cell and extracellular matrix support and controlling the release of cell growth and differentiation supporting drugs.
Keywords: Scaffold; Scaffold fabrication; Polyester; Collagen blends
Natural–origin polymers as carriers and scaffolds for biomolecules and cell delivery in tissue engineering applications
by Patrícia B. Malafaya; Gabriela A. Silva; Rui L. Reis (pp. 207-233).
The present paper intends to overview a wide range of natural–origin polymers with special focus on proteins and polysaccharides (the systems more inspired on the extracellular matrix) that are being used in research, or might be potentially useful as carriers systems for active biomolecules or as cell carriers with application in the tissue engineering field targeting several biological tissues. The combination of both applications into a single material has proven to be very challenging though. The paper presents also some examples of commercially available natural–origin polymers with applications in research or in clinical use in several applications. As it is recognized, this class of polymers is being widely used due to their similarities with the extracellular matrix, high chemical versatility, typically good biological performance and inherent cellular interaction and, also very significant, the cell or enzyme-controlled degradability. These biocharacteristics classify the natural–origin polymers as one of the most attractive options to be used in the tissue engineering field and drug delivery applications.
Keywords: Natural–origin polymers; Drug delivery; Cell delivery; Tissue engineering; Regenerative medicine; Growth factors; Biomolecules; Scaffolds; Carriers
Ceramic composites as matrices and scaffolds for drug delivery in tissue engineering
by W.J.E.M. Habraken; J.G.C. Wolke; J.A. Jansen (pp. 234-248).
Ceramic composites and scaffolds are popular implant materials in the field of dentistry, orthopedics and plastic surgery. For bone tissue engineering especially CaP-ceramics or cements and bioactive glass are suitable implant materials due to their osteoconductive properties. In this review the applicability of these ceramics but also of ceramic/polymer composites for bone tissue engineering is discussed, and in particular their use as drug delivery systems.Overall, the high density and slow biodegradability of ceramics is not beneficial for tissue engineering purposes. To address these issues, macroporosity can be introduced often in combination with osteoinductive growth factors and cells. Ceramics are good carriers for drugs, in which release patterns are strongly dependent on the chemical consistancy of the ceramic, type of drug and drug loading.Biodegradable polymers like polylactic acid, gelatin or chitosan are used as matrices for ceramic particles or as adjuvant to calcium phosphate cements. The use of these polymers can introduce a tailored biodegradation/drug release to the ceramic material.
Keywords: Abbreviations; ACP; amorphous calcium phosphate; BCP; biphasic calcium phosphate; BMP; bone morphogenic protein; BSA; bovine serum albumin; CA; carbonated apatite; CaP; calcium phosphate; CDHA; calcium deficient hydroxyapatite; DCPC; dicalcium phosphate dihydrate; bFGF; basic fibroblast growth factor; HA; hydroxyapatite; HPMC; hydroxypropylmethylcellulose; PCL; poly-e-caprolactone; PDGF; platelet derived growth factor; PEG; poly(ethylene glycol); PGA; poly(glycolic acid); PHA; poly(hydro alkanoate); PLA; poly(lactic acid); PLGA; poly(lactic-; co; -glycolic acid); PLLA; poly(; l; -; lactic acid); PPF; poly(propylene fumarate); α/β-TCP; α/β-tricalcium phosphate; TGF-β; transforming growth factor-β; TTCP; tetracalcium phosphate; VEGF; vascular endothelial growth factor.Ceramics; Cements; Bioactive glass; Ceramic/polymer composites; Drug release; Growth factors
Surface engineered and drug releasing pre-fabricated scaffolds for tissue engineering
by Hyun Jung Chung; Tae Gwan Park (pp. 249-262).
A wide range of polymeric scaffolds have been intensively studied for use as implantable and temporal devices in tissue engineering. Biodegradable and biocompatible scaffolds having a highly open porous structure and good mechanical strength are needed to provide an optimal microenvironment for cell proliferation, migration, and differentiation, and guidance for cellular in-growth from host tissue. A variety of natural and synthetic polymeric scaffolds can be fabricated in the form of a solid foam, nanofibrous matrix, microsphere, or hydrogel. Biodegradable porous scaffolds can be surface engineered to provide an extracellular matrix mimicking environment for better cell adhesion and tissue in-growth. Furthermore, scaffolds can be designed to release bioactive molecules, such as growth factors, DNA, or drugs, in a sustained manner to facilitate tissue regeneration. This paper reviews the current status of surface engineered and drug releasing scaffolds for tissue engineering.
Keywords: Scaffolds; Porous; Biomimetic; Surface modification; Drug delivery; Tissue regeneration
Injectable matrices and scaffolds for drug delivery in tissue engineering
by James D. Kretlow; Leda Klouda; Antonios G. Mikos (pp. 263-273).
Injectable matrices and depots have been the subject of much research in the field of drug delivery. The classical tissue engineering paradigm includes a matrix or scaffold to facilitate tissue growth and provide structural support, cells, and the delivery of bioactive molecules. As both tissue engineering and drug delivery techniques benefit from the use of injectable materials due to the minimal invasiveness of an injection, significant crossover should be observed between injectable materials in both fields. This review aims to outline injectable materials and processing techniques used in both tissue engineering and drug delivery and to describe methods by which current injectable materials in the field of drug delivery can be adapted for use as injectable scaffolds for tissue engineering.
Keywords: Abbreviations; APS; ammonium persulfate; DMSO; dimethyl sulfoxide; GAG; glycosaminoglycans; LCST; lower critical solution temperature; OPF; oligo(poly(ethylene glycol) fumarate); NMP; N; -methyl-2-pyrrolidone; PAA; poly(acrylic acid); PBS; phosphate buffered saline; PEG; poly(ethylene glycol); PLA; poly(lactic acid); PLGA; poly(lactic-co-glycolic acid); PNIPAAm; poly(; N; -isopropylacrylamide); PPF; poly(propylene fumarate); PVA; poly(vinyl alcohol); TEMED; N; ,; N; ,; N; ′,; N; ′-tetramethylethylenediamine.Injectable; Biomaterials; Tissue engineering; Drug delivery; Scaffolds
Matrices and scaffolds for protein delivery in tissue engineering
by Joerg K. Tessmar; Achim M. Göpferich (pp. 274-291).
The tissue engineering of functional tissues depends on the development of suitable scaffolds to support three dimensional cell growth. To improve the properties of the scaffolds, many cell carriers serve dual purposes; in addition to providing cell support, cutting-edge scaffolds biologically interact with adhering and invading cells and effectively guide cellular growth and development by releasing bioactive proteins like growth factors and cytokines.To design controlled release systems for certain applications, it is important to understand the basic principles of protein delivery as well as the stability of each applied biomolecule. To illustrate the enormous progress that has been achieved in the important field of controlled release, some of the recently developed cell carriers with controlled release capacity, including both solid scaffolds and hydrogel-derived scaffolds, are described and possible solutions for unresolved issues are illustrated.
Keywords: Drug delivery; Protein; Tissue engineering; Polymer; Scaffold; Hydrogel; Degradable; Biocompatible
Matrices and scaffolds for DNA delivery in tissue engineering
by Laura De Laporte; Lonnie D. Shea (pp. 292-307).
Regenerative medicine aims to create functional tissue replacements, typically through creating a controlled environment that promotes and directs the differentiation of stem or progenitor cells, either endogenous or transplanted. Scaffolds serve a central role in many strategies by providing the means to control the local environment. Gene delivery from the scaffold represents a versatile approach to manipulating the local environment for directing cell function. Research at the interface of biomaterials, gene therapy, and drug delivery has identified several design parameters for the vector and the biomaterial scaffold that must be satisfied. Progress has been made towards achieving gene delivery within a tissue engineering scaffold, though the design principles for the materials and vectors that produce efficient delivery require further development. Nevertheless, these advances in obtaining transgene expression with the scaffold have created opportunities to develop greater control of either delivery or expression and to identify the best practices for promoting tissue formation. Strategies to achieve controlled, localized expression within the tissue engineering scaffold will have broad application to the regeneration of many tissues, with great promise for clinical therapies.
Keywords: gene therapy; regenerative medicine; biomaterials
Matrices and scaffolds for drug delivery in dental, oral and craniofacial tissue engineering
by Eduardo K. Moioli; Paul A. Clark; Xuejun Xin; Shan Lal; Jeremy J. Mao (pp. 308-324).
Current treatments for diseases and trauma of dental, oral and craniofacial (DOC) structures rely on durable materials such as amalgam and synthetic materials, or autologous tissue grafts. A paradigm shift has taken place to utilize tissue engineering and drug delivery approaches towards the regeneration of these structures. Several prototypes of DOC structures have been regenerated such as temporomandibular joint (TMJ) condyle, cranial sutures, tooth structures and periodontium components. However, many challenges remain when taking in consideration the high demand for esthetics of DOC structures, the complex environment and yet minimal scar formation in the oral cavity, and the need for accommodating multiple tissue phenotypes. This review highlights recent advances in the regeneration of DOC structures, including the tooth, periodontium, TMJ, cranial sutures and implant dentistry, with specific emphasis on controlled release of signaling cues for stem cells, biomaterial matrices and scaffolds, and integrated tissue engineering approaches.
Keywords: Teeth; Dental pulp; Periodontium; Cranial sutures; Temporomandibular joint; Implant dentistry
Approaches to neural tissue engineering using scaffolds for drug delivery
by Stephanie M. Willerth; Shelly E. Sakiyama-Elbert (pp. 325-338).
This review seeks to give an overview of the current approaches to drug delivery from scaffolds for neural tissue engineering applications. The challenges presented by attempting to replicate the three types of nervous tissue (brain, spinal cord, and peripheral nerve) are summarized. Potential scaffold materials (both synthetic and natural) and target drugs are discussed with the benefits and drawbacks given. Finally, common methods of drug delivery, including degradable/diffusion-based delivery systems, affinity-based delivery systems, immobilized drug delivery systems, and electrically controlled drug delivery systems, are examined and critiqued. Based on the current body of work, suggestions for future directions of research in the field of neural tissue engineering are presented.
Keywords: Abbreviations; αMSH; α-melanocyte stimulating hormone; BBB; Blood–brain barrier; BCI; Brain–computer interface; BDNF; Brain derived neurotrophin factor; CNS; Central nervous system; CNTF; Ciliary neurotrophic factor; EVA; Ethylene-co-vinyl acetate; ECM; Extracellular matrix; FGF; Fibroblast growth factor; GDNF; Glial derived neurotrophic factor; IGF-1; Insulin-like growth factor-1; NGF; Nerve growth factor; NGC; Nerve guidance conduit; NT-3; Neurotrophin-3; PNS; Peripheral nervous system; PDGF; Platelet derived growth factor; PEG; Poly (ethylene glycol); PEO; Poly (ethylene oxide); PGA; Poly (glycolic acid); pHEMA; Poly (2-hydroxyethyl methacrylate); pHEMA-MMA; Poly (2-hydroxyethyl methacrylate-co-methyl methacrylate); PLA; Poly (lactic acid); PLGA; Poly (lactic-co-glycolic acid); Ppy; Polypyrrole; SCI; Spinal cord injury; TBI; Traumatic brain injury.Controlled release; Neurotrophins; Polymers; Regenerative medicine
Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage tissue engineering
by Soo-Hong Lee; Heungsoo Shin (pp. 339-359).
Regeneration of bone and cartilage defects can be accelerated by localized delivery of appropriate growth factors incorporated within biodegradable carriers. The carrier essentially allows the impregnated growth factor to release at a desirable rate and concentration, and to linger at injury sites for a sufficient time to recruit progenitors and stimulate tissue healing processes. In addition, the carrier can be formulated to have particular structure to facilitate cellular infiltration and growth. In this review, we present a summary of growth factor delivery carrier systems for bone and cartilage tissue engineering. Firstly, we describe a list of growth factors implicated in repair and regeneration of bone and cartilage by addressing their biological effects at different stages of the healing process. General requirements for localized growth factor delivery carriers are then discussed. We also provide selective examples of material types (natural and synthetic polymers, inorganic materials, and their composites) and fabricated forms of the carrier (porous scaffolds, microparticles, and hydrogels), highlighting the dose-dependent efficacy, release kinetics, animal models, and restored tissue types. Extensive discussion on issues involving currently investigated carriers for bone and cartilage tissue engineering approaches may illustrate future paths toward the development of an ideal growth factor delivery system.
Keywords: Abbreviations; ACI; autologous chondrocyte implantation; ACS; absorbable collagen sponge; BMSC; bone marrow-derived stem cells; CT; computed tomography; FGF-2; fibroblast growth factor-2; BMP; bone morphogenetic protein; rhBMP; recombinant human bone morphogenetic protein; CPC; calcium phosphate cement; ECM; extracellular matrix; HA; hydroxyapatite; IGF-I; insulin-like growth factor-I; MMP; matrix metalloproteinase; MP; microparticle; MSC; mesenchymal stem cell; PCL; poly(caprolactone); PDGF; platelet-derived growth factor; PEG; poly(ethylene glycol); PGA; poly(glycolic acid); PLA; poly(; d; ,; l; -lactic acid); PLGA; poly(lactic-co-glycolic acid); PLLA; poly(; l; -lactic acid); PPF; poly(propylene fumarate); SFF; solid free form; βTCP; β-tricalciumphosphate; TGF-β1; transforming growth factor-β1; rhTGF-β1; recombinant human transforming growth factor-β1; TIMP-1; tissue inhibitors of MMP; VEGF; vascular endothelial growth factorMatrices; Scaffold; Bioactive molecule; Bone tissue engineering; Cartilage regeneration
Matrices and scaffolds for drug delivery in vascular tissue engineering
by Ge Zhang; Laura J. Suggs (pp. 360-373).
The purpose of this review is to give an overview of strategies using natural and artificial substrates to present active biomolecules in the development of vascular structures. Two primary topics are discussed. The first is the replacement and augmentation of arteries using vascular grafts or stents. Second is the recruitment of microvasculature secondary to an ischemic event or for the purpose of developing perfused, large-volume tissue-engineered constructs. Significant overlap exists among these topics. The focus is therefore on specific drug delivery strategies with discussion of a number of emerging themes. Where applicable, results from clinical trials have been included. Early work in the field includes covalent and nonspecific immobilization of growth factors, while more recent work emphasizes biologically inspired control over localization and temporal presentation. Novel strategies for matrix-mediated release can deliver multiple growth factors and/or cells in a manner that mimics tissue development and healing. Challenges that remain within this field center on controlling reciprocal interactions among the three fundamental tissue engineering components of scaffolds, cells and signals.
Keywords: Drug delivery; Scaffold; Vascular disease
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