Editorial

513ISSN 1743-588910.2217/NNM.13.36 © 2013 Future Medicine Ltd Nanomedicine (2013) 8(4), 513–515

“The use of pharmaceutical technology gives advantages such as the efficient transport of drugs, leading to improved target-specific absorption, controlled release, biocompatibility

and reduced phototoxicity.”

Fernando Lucas PrimoNanophoton® Company, Saudade Avenue, 2478, Room 3, Ribeirão Preto, São Paulo State, 14085-000, Brazil

Antonio Claudio TedescoAuthor for correspondence: Photobiology & Photomedicine Research Group, Nanobiotechnology & Tissue Engineering Center, São Paulo University, Bandeirantes Avenue, 3900, Ribeirão Preto, São Paulo State, 14040-901, Brazil atedesco@usp.br

Combining photobiology and nanobiotechnology: a step towards improving medical protocols based on advanced biological models

are used clinically in the USA, Europe and Brazil for treatment of burns;

�� Cellular therapies that are based on the appli-cation of a cell-free solution or combined with biocompatible systems to induce repair and regeneration of organs and tissues, predominantly stem cell therapy [7];

�� Development of prosthesis and devices that mimic human tissues for replacement and/or treatment of injuries and damaged organs, such as bone structures, muscles, tendons, car-tilage and cardiac device components (valves, ventricular and coronary blood vessels), involv-ing the use of synthetic and natural polymers with high biological compatibility in the preparation of parts and prosthetic grafts.

Dermal equivalents Early studies involving the development of tissue models were carried out in the late 1970s, and sought to obtain dermal equivalents (DEs) that reproduce the majority of conditions in in vivo human skin [4,8]. Initially, models were obtained by extensive, highly complex experimental stages. The precursors of DEs partially mimicked the skin tissue, representing each layer individually. Bell and colleagues pioneered the preparation of modern models with a 3D structure from a com-bination of cultured fibroblasts, keratinocytes and collagen matrix [8].

Currently, DEs are used as substitutes for human skin in different technological fields such as molecular biology, pharmacology, cosmetics, TE and clinical medicine [9,10]. DEs are excel-lent tools to investigate the extracellular matrix, which is considered to be the support base of tis-sues. Recent studies have demonstrated that the extracellular matrix is based on specific proteins

Tissue engineering (TE) was first presented at the 1st Meeting of the National Science Foundation (NSF) in 1988 in the USA [1]. TE was defined as the application of principles and methods of engi-neering and life sciences for the understanding of the structure and function of healthy tissues and pathologies, and the development of new bio-logical substitutes for the repair or regeneration of tissues and organs [2]. TE differs from tradi-tional therapies because it allows the permanent integration of the prosthesis/graft in the patient. The technique is an emerging multidisciplinary field of science, combining principles of biology and engineering to develop viable substitutes that restore and maintain the function of human tissues [3,4].

During the 1990s, TE progressed rapidly and various types of structures were developed to be used as biological tissue equivalents. Most of these biomaterials usually reached the market a short time after development, with a strong growth of annual revenues in the global biotechnology sec-tor (~US$3.5 billion in 2012) [5]. TE has been used as a potential alternative to transplantation of organs and tissues. The neo-organs and tissues obtained by TE are functionalized and deployed simultaneously with clinical treatments or thera-pies, in parallel with enzymes and reconstructive surgery for rehabilitation of the original function of the injured region. For example, this has been used for the replacement and regeneration of the liver and parts of the gastrointestinal system [6].

Currently, TE is divided into three areas:

�� In vitro growth and development of tissues and implants to repair damaged regions using 3D equivalents. Generally, implants are prepared from primary culture of cells under special conditions to obtain 3D model tissue. A com-mon example is the use of skin grafts, which

KEYWORDS: dermal equivalent n nanobiotechnology n photodynamic process n phthalocyanine n tissue engineering

SPECIAL FOCUS y Advanced nanobiomaterials for tissue engineering and regenerative medicine

part of

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and polysaccharides (e.g., collagen, elastin and metalloenzymes) secreted into the intercellular environment, leading to biochemical pheno-mena that differ according to type and location of tissue, and directly influence the growth, stages of cell proliferation, wound healing and tissue regeneration. From a better understand-ing of tissue composition and structure it was possible to improve dimensional models that suc-cessfully mimic the human dermal extracellular matrix. Consequently, several scientific studies have emerged, evaluating the behavior of extra-cellular collagen matrix. These studies monitored growth and migration, and phenomena related to repair and regeneration, via histological evalua-tions, and techniques that allow the identifica-tion of metabolites associated with growth and tissue healing, such as immunodetection, western blotting and zymography [11].

Recently, interest in photobiology and low-level lasers has increased exponentially, with therapeutic applications in the fields such as tissue repair and wound healing, analgesic and anti-inflammatory delivery for the elimination of skin depressions, and antibacterial activity [12,13].

“Recently, pharmaceutical technology has greatly contributed to the development of

drug delivery systems by applying nanotechnology to therapeutic applications.”

For a long time, photodynamic processes (PDPs) were used to treat certain types of un -pigmented cancer, with promising results obtained in clinical studies in Brazil and many countries worldwide [13–15]. The efficiency of PDPs has been established over time, by the sim-plicity and versatility of the protocols based on the combination of a photosensitive drug and visible light (typically from a continuous or diode laser, or LED light source), which are relatively harm-less themselves, but when combined together in the presence of molecular oxygen in the bio logical tissue, they induce the desired response [16]. PDP

mechanisms are characterized by a sequence of biological events, including photo-oxidation, reactive oxygen species production (mainly singlet oxygen), vascular damage, mitochondrial photo-activation and photobiostimulation processes (normally induced by visible light therapy selected at a suitable wavelengths at a low energy level).

The efficiency of PDP is directly related to the ability of the photosensitive drug to be administered in a biocompatible manner, with an adequate biodistribution [17]. Recently, pharma ceutical technology has greatly con-tributed to the development of drug delivery systems by applying nanotechnology to thera-peutic applications [7,14,18]. Commercial prod-ucts that use advanced delivery systems have been developed, using a photosensitive drug for systemic and/or topical treatment of cancer (photodynamic therapy) [18,19].

The use of pharmaceutical technology gives advantages such as the efficient transport of drugs, leading to improved target-specific absorp-tion, controlled release, biocompatibility and reduced phototoxicity [20].

The combination of these three fields of research, hailed as a ‘new frontier of science’, (nanobiotechnology, PDPs and TE), applied to areas such as cancer, neurodegenerative diseases, organ transplantation will be a challenge, but could ultimately be promising for achieving a better and longer life.

Financial & competing interests disclosureThis work was supported by the FAPESP Thematic Research Projects (#2008/53719-4 and #2007/58809-9 to AC Tedesco), FAPESP Post-doc (#2009/15363-9 to FL Primo) and CNPq RHAE/Project (#551568/2011-9 to FL Primo). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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