Special Issue "Tissue-Protective Agents: New Drugs and Technologies"

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (31 December 2017)

Special Issue Editors

Guest Editor
Prof. Dr. Simona Collina

Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section,University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy
Website | E-Mail
Interests: rational drug design, synthesis and structure-activity relationships of biologically active compounds (small molecules and peptides); preparation and characterization of chiral compounds, discovery of new modulators of sigma receptors as well as of small molecules able to affect the protein kinase C (PKC)/ELAV proteins/mRNA system
Guest Editor
Prof. Dr. Silvia Rossi

Dept Drug Sciences, University of Pavia, Viale Taramelli, 12, 27100 Pavia –I, Italy
Website | E-Mail
Interests: rheology and viscosimetry; mucoadhesion; in situ gelling polymers; micro- and nanoparticulate systems; statistical optimization techniques; wound dressings, nervous tissue repair

Special Issue Information

Dear Colleagues,

Tissue-regeneration is one of the most important challenges in the biomedical field. The recovery of damaged tissue is essential for slowing and reverting the progression of lesions and for restoring tissue functions, particularly when the damage is caused by severe traumatic events, by aging, or age-associated degenerative diseases. The classical approach based on drug treatment, traditionally aimed to specific target proteins, has been recently combined with cell therapy and with the use of technological platforms able to play an active role in repairing/regeneration mechanisms. This could provide important advancements in developing alternative, complementary and more efficacious treatments. Such a goal can be achieved by integrating several disciplines, i.e., medicinal chemistry, pharmaceutical technology, pharmacology and engineering.

This Special Issue intends to summarize the current state-of-the-art in this field; the proposed topics include, but are not limited to:

  • new potential drugs able to promote tissue repair/regeneration 
  • analytical strategies for bioactive compound identification and quantification
  • bioactive therapeutic platforms able to load the actives, maintaining their therapeutic properties and enhancing their efficacy
  • polymeric scaffolds able to support cell proliferation and migration
  • cell therapy approach
  • in vitro/ex vivo techniques for the investigation of active mechanisms
  • in vivo preclinical and clinical studies to prove treatment efficacy

To celebrate the advances in this important field, the Pharmaceuticals journal invites fellow scientists to submit original papers or reviews, which will be published as a Special Issue.

Prof. Dr. Simona Collina
Prof. Dr. Silvia Rossi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 850 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (7 papers)

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Research

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Open AccessArticle Effects of Polymethoxyflavonoids on Bone Loss Induced by Estrogen Deficiency and by LPS-Dependent Inflammation in Mice
Pharmaceuticals 2018, 11(1), 7; https://doi.org/10.3390/ph11010007
Received: 29 November 2017 / Revised: 11 January 2018 / Accepted: 18 January 2018 / Published: 20 January 2018
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Abstract
Polymethoxyflavonoids (PMFs) are a family of the natural compounds that mainly compise nobiletin, tangeretin, heptamethoxyflavone (HMF), and tetramethoxyflavone (TMF) in citrus fruits. PMFs have shown various biological functions, including anti-oxidative effects. We previously showed that nobiletin, tangeretin, and HMF all inhibited interleukin (IL)-1-mediated [...] Read more.
Polymethoxyflavonoids (PMFs) are a family of the natural compounds that mainly compise nobiletin, tangeretin, heptamethoxyflavone (HMF), and tetramethoxyflavone (TMF) in citrus fruits. PMFs have shown various biological functions, including anti-oxidative effects. We previously showed that nobiletin, tangeretin, and HMF all inhibited interleukin (IL)-1-mediated osteoclast differentiation via the inhibition of prostaglandin E2 synthesis. In this study, we created an original mixture of PMFs (nobiletin, tangeretin, HMF, and TMF) and examined whether or not PMFs exhibit co-operative inhibitory effects on osteoclastogenesis and bone resorption. In a coculture of bone marrow cells and osteoblasts, PMFs dose-dependently inhibited IL-1-induced osteoclast differentiation and bone resorption. The optimum concentration of PMFs was lower than that of nobiletin alone in the suppression of osteoclast differentiation, suggesting that the potency of PMFs was stronger than that of nobiletin in vitro. The oral administration of PMFs recovered the femoral bone loss induced by estrogen deficiency in ovariectomized mice. We further tested the effects of PMFs on lipopolysaccharide-induced bone resorption in mouse alveolar bone. In an ex vivo experimental model for periodontitis, PMFs significantly suppressed the bone-resorbing activity in organ cultures of mouse alveolar bone. These results indicate that a mixture of purified nobiletin, tangeretin, HMF, and TMF exhibits a co-operative inhibitory effect for the protection against bone loss in a mouse model of bone disease, suggesting that PMFs may be potential candidates for the prevention of bone resorption diseases, such as osteoporosis and periodontitis. Full article
(This article belongs to the Special Issue Tissue-Protective Agents: New Drugs and Technologies)
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Open AccessArticle Systemic Interleukin-4 Administration after Spinal Cord Injury Modulates Inflammation and Promotes Neuroprotection
Pharmaceuticals 2017, 10(4), 83; https://doi.org/10.3390/ph10040083
Received: 7 September 2017 / Revised: 17 October 2017 / Accepted: 22 October 2017 / Published: 24 October 2017
Cited by 5 | PDF Full-text (5037 KB) | HTML Full-text | XML Full-text
Abstract
Traumatic spinal cord injury (SCI) causes dramatic disability and dysfunction in the motor, sensory and autonomic systems. The severe inflammatory reaction that occurs after SCI is strongly associated with further tissue damage. As such, immunomodulatory strategies have been developed, aimed at reducing inflammation, [...] Read more.
Traumatic spinal cord injury (SCI) causes dramatic disability and dysfunction in the motor, sensory and autonomic systems. The severe inflammatory reaction that occurs after SCI is strongly associated with further tissue damage. As such, immunomodulatory strategies have been developed, aimed at reducing inflammation, but also at shaping the immune response in order to protect, repair and promote regeneration of spared neural tissue. One of those promising strategies is the intraspinal administration of the cytokine interleukin-4 (IL-4) that was shown to promote a phenotype on specific immune cells associated with neuroprotection and repair. In this work, we evaluated if a systemic delivery of IL-4 for a 7-days period was also capable of promoting neuroprotection after SCI by analyzing different neural cells populations and motor recovery. IL-4 treatment promoted an elevation of the anti-inflammatory cytokine IL-10 in the serum both at 24 h and 7 days after injury. Locally, treatment with IL-4 led to a reduction on cells expressing markers associated with inflammation, CD11b/c and iNOS. Importantly, IL-4 treatment increased the neuronal markers βIII-tubulin and NeuN, and the oligodendrocyte marker O4, suggesting a neuroprotective effect. Moreover, 100% of the animals treated with IL-4 were able to recover weight support against only 33% of saline treated animals. Overall, these results show that systemic administration of IL-4 positively impacts different aspects of spinal cord injury, creating a more favorable environment for recovery to take place. Full article
(This article belongs to the Special Issue Tissue-Protective Agents: New Drugs and Technologies)
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Open AccessArticle Exploring Wound-Healing Genomic Machinery with a Network-Based Approach
Pharmaceuticals 2017, 10(2), 55; https://doi.org/10.3390/ph10020055
Received: 11 May 2017 / Revised: 13 June 2017 / Accepted: 14 June 2017 / Published: 21 June 2017
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Abstract
The molecular mechanisms underlying tissue regeneration and wound healing are still poorly understood despite their importance. In this paper we develop a bioinformatics approach, combining biology and network theory to drive experiments for better understanding the genetic underpinnings of wound healing mechanisms and [...] Read more.
The molecular mechanisms underlying tissue regeneration and wound healing are still poorly understood despite their importance. In this paper we develop a bioinformatics approach, combining biology and network theory to drive experiments for better understanding the genetic underpinnings of wound healing mechanisms and for selecting potential drug targets. We start by selecting literature-relevant genes in murine wound healing, and inferring from them a Protein-Protein Interaction (PPI) network. Then, we analyze the network to rank wound healing-related genes according to their topological properties. Lastly, we perform a procedure for in-silico simulation of a treatment action in a biological pathway. The findings obtained by applying the developed pipeline, including gene expression analysis, confirms how a network-based bioinformatics method is able to prioritize candidate genes for in vitro analysis, thus speeding up the understanding of molecular mechanisms and supporting the discovery of potential drug targets. Full article
(This article belongs to the Special Issue Tissue-Protective Agents: New Drugs and Technologies)
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Open AccessArticle In Vitro and In Vivo Studies of Alar-Nasal Cartilage Using Autologous Micro-Grafts: The Use of the Rigenera® Protocol in the Treatment of an Osteochondral Lesion of the Nose
Pharmaceuticals 2017, 10(2), 53; https://doi.org/10.3390/ph10020053
Received: 28 April 2017 / Revised: 7 June 2017 / Accepted: 9 June 2017 / Published: 13 June 2017
Cited by 3 | PDF Full-text (1820 KB) | HTML Full-text | XML Full-text
Abstract
Cartilage defects represent a serious problem due to the poor regenerative properties of this tissue. Regarding the nose, nasal valve collapse is associated with nasal blockage and persistent airway obstruction associated with a significant drop in the quality of life for patients. In [...] Read more.
Cartilage defects represent a serious problem due to the poor regenerative properties of this tissue. Regarding the nose, nasal valve collapse is associated with nasal blockage and persistent airway obstruction associated with a significant drop in the quality of life for patients. In addition to surgical techniques, several cell-based tissue-engineering strategies are studied to improve cartilage support in the nasal wall, that is, to ameliorate wall insufficiency. Nevertheless, there are no congruent data available on the benefit for patients during the follow-up time. In this manuscript, we propose an innovative approach in the treatment of cartilage defects in the nose (nasal valve collapse) based on autologous micro-grafts obtained by mechanical disaggregation of a small portion of cartilage tissue (Rigenera® protocol). In particular, we first analyzed in vitro murine and human cartilage micro-grafts; secondly, we analyzed the clinical results of a patient with pinched nose deformity treated with autologous micro-grafts of chondrocytes obtained by Rigenera® protocol. The use of autologous micro-graft produced promising results in surgery treatment of cartilage injuries and could be safely and easily administrated to patients with cartilage tissue defects. Full article
(This article belongs to the Special Issue Tissue-Protective Agents: New Drugs and Technologies)
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Review

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Open AccessReview Biodegradable Scaffolds for Bone Regeneration Combined with Drug-Delivery Systems in Osteomyelitis Therapy
Pharmaceuticals 2017, 10(4), 96; https://doi.org/10.3390/ph10040096
Received: 1 October 2017 / Revised: 27 November 2017 / Accepted: 29 November 2017 / Published: 12 December 2017
Cited by 7 | PDF Full-text (1308 KB) | HTML Full-text | XML Full-text
Abstract
A great deal of research is ongoing in the area of tissue engineering (TE) for bone regeneration. A possible improvement in restoring damaged tissues involves the loading of drugs such as proteins, genes, growth factors, antibiotics, and anti-inflammatory drugs into scaffolds for tissue [...] Read more.
A great deal of research is ongoing in the area of tissue engineering (TE) for bone regeneration. A possible improvement in restoring damaged tissues involves the loading of drugs such as proteins, genes, growth factors, antibiotics, and anti-inflammatory drugs into scaffolds for tissue regeneration. This mini-review is focused on the combination of the local delivery of antibiotic agents with bone regenerative therapy for the treatment of a severe bone infection such as osteomyelitis. The review includes a brief explanation of scaffolds for bone regeneration including scaffolds characteristics and types, a focus on severe bone infections (especially osteomyelitis and its treatment), and a literature review of local antibiotic delivery by the combination of scaffolds and drug-delivery systems. Some examples related to published studies on gentamicin sulfate-loaded drug-delivery systems combined with scaffolds are discussed, and future perspectives are highlighted. Full article
(This article belongs to the Special Issue Tissue-Protective Agents: New Drugs and Technologies)
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Open AccessReview Nanofiber Scaffolds as Drug Delivery Systems to Bridge Spinal Cord Injury
Pharmaceuticals 2017, 10(3), 63; https://doi.org/10.3390/ph10030063
Received: 10 May 2017 / Revised: 13 June 2017 / Accepted: 1 July 2017 / Published: 5 July 2017
Cited by 7 | PDF Full-text (1347 KB) | HTML Full-text | XML Full-text
Abstract
The complex pathophysiology of spinal cord injury (SCI) may explain the current lack of an effective therapeutic approach for the regeneration of damaged neuronal cells and the recovery of motor functions. A primary mechanical injury in the spinal cord triggers a cascade of [...] Read more.
The complex pathophysiology of spinal cord injury (SCI) may explain the current lack of an effective therapeutic approach for the regeneration of damaged neuronal cells and the recovery of motor functions. A primary mechanical injury in the spinal cord triggers a cascade of secondary events, which are involved in SCI instauration and progression. The aim of the present review is to provide an overview of the therapeutic neuro-protective and neuro-regenerative approaches, which involve the use of nanofibers as local drug delivery systems. Drugs released by nanofibers aim at preventing the cascade of secondary damage (neuro-protection), whereas nanofibrous structures are intended to re-establish neuronal connectivity through axonal sprouting (neuro-regeneration) promotion, in order to achieve a rapid functional recovery of spinal cord. Full article
(This article belongs to the Special Issue Tissue-Protective Agents: New Drugs and Technologies)
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Open AccessReview PKC in Regenerative Therapy: New Insights for Old Targets
Pharmaceuticals 2017, 10(2), 46; https://doi.org/10.3390/ph10020046
Received: 3 April 2017 / Revised: 12 May 2017 / Accepted: 16 May 2017 / Published: 18 May 2017
Cited by 1 | PDF Full-text (3678 KB) | HTML Full-text | XML Full-text
Abstract
Effective therapies for chronic or non-healing wounds are still lacking. These tissue insults often result in severe clinical complications (i.e., infections and/or amputation) and sometimes lead to patient death. Accordingly, several research groups have focused their efforts in finding innovative and powerful therapeutic [...] Read more.
Effective therapies for chronic or non-healing wounds are still lacking. These tissue insults often result in severe clinical complications (i.e., infections and/or amputation) and sometimes lead to patient death. Accordingly, several research groups have focused their efforts in finding innovative and powerful therapeutic strategies to overcome these issues. On the basis of these considerations, the comprehension of the molecular cascades behind these pathological conditions could allow the identification of molecules against chronic wounds. In this context, the regulation of the Protein Kinase C (PKC) cascade has gained relevance in the prevention and/or reparation of tissue damages. This class of phosphorylating enzymes has already been considered for different physiological and pathological pathways and modulation of such enzymes may be useful in reparative processes. Herein, the recent developments in this field will be disclosed, highlighting the pivotal role of PKC α and δ in regenerative medicine. Moreover, an overview of well-established PKC ligands, acting via the modulation of these isoenzymes, will be deeply investigated. This study is aimed at re-evaluating widely known PKC modulators, currently utilized for treating other diseases, as fruitful molecules in wound-healing. Full article
(This article belongs to the Special Issue Tissue-Protective Agents: New Drugs and Technologies)
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