Molecular Changes Underlying Genistein Treatment of Wound Healing: A Review.

Estrogen deprivation is one of the major factors responsible for many age-related processes including poor wound healing in postmenopausal women. However, the reported side-effects of estrogen replacement therapy (ERT) have precluded broad clinical administration. Therefore, selective estrogen receptor modulators (SERMs) have been developed to overcome the detrimental side effects of ERT on breast and/or uterine tissues. The use of natural products isolated from plants (e.g., soy) may represent a promising source of biologically active compounds (e.g., genistein) as efficient alternatives to conventional treatment. Genistein as natural SERM has the unique ability to selectively act as agonist or antagonist in a tissue-specific manner, i.e., it improves skin repair and simultaneously exerts anti-cancer and chemopreventive properties. Hence, we present here a wound healing phases-based review of the most studied naturally occurring SERM.

Recent trends in natural polysaccharide based bioinks for multiscale 3D printing in tissue regeneration: A review.

Biofabrication by three-dimensional (3D) printing has been an attractive technology in harnessing the possibility to print anatomical shaped native tissues with controlled architecture and resolution. 3D printing offers the possibility to reproduce complex microarchitecture of native tissues by printing live cells in a layer by layer deposition to provide a biomimetic structural environment for tissue formation and host tissue integration. Plant based biomaterials derived from green and sustainable sources have represented to emulate native physicochemical and biological cues in order to direct specific cellular response and formation of new tissues through biomolecular recognition patterns. This comprehensive review aims to analyze and identify the most commonly used plant based bioinks for 3D printing applications. An overview on the role of different plant based biomaterial of terrestrial origin (Starch, Nanocellulose and Pectin) and marine origin (Ulvan, Alginate, Fucoidan, Agarose and Carrageenan) used for 3D printing applications are discussed elaborately. Furthermore, this review will also emphasis in the functional aspects of different 3D printers, appropriate printing material, merits and demerits of numerous plant based bioinks in developing 3D printed tissue-like constructs. Additionally, the underlying potential benefits, limitations and future perspectives of plant based bioinks for tissue engineering (TE) applications are also discussed.

Safety, pitfalls, and misunderstandings about the use of ozone therapy as a regenerative medicine tool. A narrative review.

Despite various opinions and healthy controversy on Ozone Therapy (OT), the practices of this therapy have increased worldwide. Main areas of study with consistent scientific outcomes are the topical treatment of both disk herniation and periodontal disease. On the other hand, there is a net dissociation of the scientific resonance concerning systemic oxygen/ozone treatments. It is our intention to discuss in logical terms the numerous papers that commendably reported adverse reactions attributable to OT, focusing our attention mainly to the techniques of administration and not to the simple contact of ozone with biological material. The case reports on OT treatments safety concerns discussed on international journals, make it possible to state that most safety issues are secondary to infections or traumatic reactions due to malpractice. Commonly, the molecule of ozone itself is not responsible of severe reactions at the therapeutic modalities. The millions of patients treated so far from the thousands of physicians correctly practicing OT world widely in the last 40 years demonstrate the safety of this simple and cost-effective regenerative medicine tool. The promising therapeutic implications also for the current COVID-19 emergency are a further stimulus to the standardization of this therapeutic resource with multiple application specificities.

Growing a backbone - functional biomaterials and structures for intervertebral disc (IVD) repair and regeneration: challenges, innovations, and future directions.

Back pain and associated maladies can account for an immense amount of healthcare cost and loss of productivity in the workplace. In particular, spine related injuries in the US affect upwards of 5.7 million people each year. The degenerative disc disease treatment almost always arises due to a clinical presentation of pain and/or discomfort. Preferred conservative treatment modalities include the use of non-steroidal anti-inflammatory medications, physical therapy, massage, acupuncture, chiropractic work, and dietary supplements like glucosamine and chondroitin. Artificial disc replacement, also known as total disc replacement, is a treatment alternative to spinal fusion. The goal of artificial disc prostheses is to replicate the normal biomechanics of the spine segment, thereby preventing further damage to neighboring sections. Artificial functional disc replacement through permanent metal and polymer-based components continues to evolve, but is far from recapitulating native disc structure and function, and suffers from the risk of unsuccessful tissue integration and device failure. Tissue engineering and regenerative medicine strategies combine novel material structures, bioactive factors and stem cells alone or in combination to repair and regenerate the IVD. These efforts are at very early stages and a more in-depth understanding of IVD metabolism and cellular environment will also lead to a clearer understanding of the native environment which the tissue engineering scaffold should mimic. The current review focusses on the strategies for a successful regenerative scaffold for IVD regeneration and the need for defining new materials, environments, and factors that are so finely tuned in the healthy human intervertebral disc in hopes of treating such a prevalent degenerative process.

Recent advances in gelatin-based therapeutics.

INTRODUCTION: Biomaterials have provided a wide range of exciting opportunities in tissue engineering and regenerative medicine. Gelatin, a collagen-derived natural biopolymer, has been extensively used in regenerative medicine applications over the years, due to its cell-responsive properties and the capacity to deliver a wide range of biomolecules. AREAS COVERED: The most relevant properties of gelatin as biomaterial are presented together with its main therapeutic applications. The latter includes drug delivery systems, tissue engineering approaches, potential uses as ink for 3D/4D Bioprinting, and its relevance in organ-on-a-chip platforms. EXPERT OPINION: Advances in polymer chemistry, mechanobiology, imaging technologies, and 3D biofabrication techniques have expanded the application of gelatin in multiple biomedical research applications ranging from bone and cartilage tissue engineering, to wound healing and anti-cancer therapy. Here, we highlight the latest advances in gelatin-based approaches within the fields of biomaterial-based drug delivery and tissue engineering together with some of the most relevant challenges and limitations.

Medicinal Plants in Tissue Engineering and Regenerative Medicine in the African Continent.

IMPACT STATEMENT: Medicinal plants are used by various traditional healers to alleviate the signs and symptoms associated with numerous diseases such as osteoarthritis, asthma, cancer, heart disease, tuberculosis, swollen ankles, bone fracture, malaria, convulsion, piles, hypertension, typhoid fever, diabetes, and anemia. Our research is relevant to communities that rely solely on traditional medicine for their well-being.

Defective Black Nano-Titania Thermogels for Cutaneous Tumor-Induced Therapy and Healing.

Current challenges in cutaneous tumor therapy are healing the skin wounds resulting from surgical resection and eliminating possible residual tumor cells to prevent recurrence. To address this issue, bifunctional biomaterials equipped with effective tumor therapeutic capacity for skin cancers and simultaneous tissue regenerative ability for wound closure are highly recommended. Herein, we report an injectable thermosensitive hydrogel (named BT-CTS thermogel) with the integration of nanosized black titania (B-TiO2- x, ∼50 nm) nanoparticles into a chitosan (CTS) matrix. The B-TiO2- x nanocrystal exhibits a crystalline/amorphous core-shell structure with abundant oxygen vacancies, which endows the BT-CTS thermogels with simultaneous photothermal therapy (PTT) and photodynamic therapy (PDT) effects under single-wavelength near-infrared laser irradiation, leading to an excellent therapeutic effect on skin tumors in vitro and in vivo. Moreover, the BT-CTS thermogel not only supports the adhesion, proliferation, and migration of normal skin cells but also facilitates skin tissue regeneration in a murine chronic wound model. Therefore, such BT-CTS thermogels with easy injectability, excellent thermostability, and simultaneous PTT and PDT efficacy as well as tissue regenerative activity offers a promising pathway for the healing of cutaneous tumor-induced wounds.

Static Magnetic Field (SMF) as a Regulator of Stem Cell Fate - New Perspectives in Regenerative Medicine Arising from an Underestimated Tool.

Tissue engineering and stem cell-based therapies are one of the most rapidly developing fields in medical sciences. Therefore, much attention has been paid to the development of new drug-delivery systems characterized by low cytotoxicity, high efficiency and controlled release. One of the possible strategies to achieve these goals is the application of magnetic field and/or magnetic nanoparticles, which have been shown to exert a wide range of effects on cellular metabolism. Static magnetic field (SMF) has been commonly used in medicine as a tool to increase wound healing, bone regeneration and as a component of magnetic resonance technique. However, recent data shed light on deeper mechanism of SMF action on physiological properties of different cell populations, including stem cells. In the present review, we focused on SMF effects on stem cell biology and its possible application as a tool for controlled drug delivery. We also highlighted the perspectives, in which SMF can be used in future therapies in tissue engineering due to its easy application and a wide range of possible effects on cells and organisms.

Regenerative Sports Medicine: Past, Present, and Future (Adapted From the PASSOR Legacy Award Presentation; AAPMR; October 2016).

Regenerative medicine has shown dramatic expanse and evolution in the past decade. Within that milieu, physiatrists are taking an active role in research, clinical care delivery, and education. The purpose of this review is to provide a balance among evidence, theory, experience, clinical trends, and the foreseeable future. We focus on the literature that reports the research with the best methodology in each practice area, recognizing that the level of evidence varies substantially among different treatment modalities and conditions. The following elements are included: an overview of the evolution of currently available regenerative techniques, evidence base for each available modality (prolotherapy, platelet rich plasma, bone marrow aspirate concentrate and stem cells, adipose-derived stem cells, and amniotic tissue products), general principles in the application of these treatments, and discussion and a vision of what lies ahead. We expect that practitioners will use this review to facilitate clinical decision making and to provide a core knowledge base to assist when counseling patients. LEVEL OF EVIDENCE: IV.

How far have biological therapies come in regenerative sports medicine?

INTRODUCTION: Regular engagement in sports produces many health benefits, but also exposes to increased injury risk. The quality of medical care available is crucial not only for sports trauma but also to avoid overuse syndromes and post-traumatic degenerative conditions. AREAS COVERED: We provide background information on some clinical needs in sport injuries and describe the main families of biological products used in clinical practice. We also discuss limitations of the current clinical experience. EXPERT OPINION: Sport and exercise impairment affects different segments of the population with different needs. The exceptional demands of elite athletes and subsequent media coverage have created hype around regenerative therapies. Statistical evidence, whether weak (cell products) or moderate (PRPs), is not enough to drive medical decisions because of the heterogeneity of the biological products available and their application procedures. Moreover, the specific needs of the different segments of the population along with the available clinical evidence for each musculoskeletal condition should be considered in the decision-making process. There is urgent need to develop regenerative protocols combined with post-intervention rehabilitation, and gather meaningful clinical data on the safety and efficacy of these interventions in the different populations segments.

Stem Cell Technology for (Epi)genetic Brain Disorders.

Despite the enormous efforts of the scientific community over the years, effective therapeutics for many (epi)genetic brain disorders remain unidentified. The common and persistent failures to translate preclinical findings into clinical success are partially attributed to the limited efficiency of current disease models. Although animal and cellular models have substantially improved our knowledge of the pathological processes involved in these disorders, human brain research has generally been hampered by a lack of satisfactory humanized model systems. This, together with our incomplete knowledge of the multifactorial causes in the majority of these disorders, as well as a thorough understanding of associated (epi)genetic alterations, has been impeding progress in gaining more mechanistic insights from translational studies. Over the last years, however, stem cell technology has been offering an alternative approach to study and treat human brain disorders. Owing to this technology, we are now able to obtain a theoretically inexhaustible source of human neural cells and precursors in vitro that offer a platform for disease modeling and the establishment of therapeutic interventions. In addition to the potential to increase our general understanding of how (epi)genetic alterations contribute to the pathology of brain disorders, stem cells and derivatives allow for high-throughput drugs and toxicity testing, and provide a cell source for transplant therapies in regenerative medicine. In the current chapter, we will demonstrate the validity of human stem cell-based models and address the utility of other stem cell-based applications for several human brain disorders with multifactorial and (epi)genetic bases, including Parkinson's disease (PD), Alzheimer's disease (AD), fragile X syndrome (FXS), Angelman syndrome (AS), Prader-Willi syndrome (PWS), and Rett syndrome (RTT).

Human induced pluripotent stem cells: A disruptive innovation.

This year (2016) will mark the 10th anniversary of the discovery of induced pluripotent stem cells (iPSCs). The finding that the transient expression of four transcription factors can radically remodel the epigenome, transcriptome and metabolome of differentiated cells and reprogram them into pluripotent stem cells has been a major and groundbreaking technological innovation. In this review, we discuss the major applications of this technology that we have grouped in nine categories: a model to study cell fate control; a model to study pluripotency; a model to study human development; a model to study human tissue and organ physiology; a model to study genetic diseases in a dish; a tool for cell rejuvenation; a source of cells for drug screening; a source of cells for regenerative medicine; a tool for the production of human organs in animals.

Advanced cell therapies: targeting, tracking and actuation of cells with magnetic particles.

Regenerative medicine would greatly benefit from a new platform technology that enabled measurable, controllable and targeting of stem cells to a site of disease or injury in the body. Superparamagnetic iron-oxide nanoparticles offer attractive possibilities in biomedicine and can be incorporated into cells, affording a safe and reliable means of tagging. This review describes three current and emerging methods to enhance regenerative medicine using magnetic particles to guide therapeutic cells to a target organ; track the cells using MRI and assess their spatial localization with high precision and influence the behavior of the cell using magnetic actuation. This approach is complementary to the systemic injection of cell therapies, thus expanding the horizon of stem cell therapeutics.

The emerging use of platelet-rich plasma in musculoskeletal medicine.

Platelet-rich plasma (PRP) is one of many new developments within the expanding field of regenerative medicine. Specialists in areas such as orthopedics, physical medicine and rehabilitation, and rheumatology have been exploring the benefits of this novel therapy. Although PRP therapy remains controversial and has minimal clinical trial support, the use of orthobiologics such as PRP continues to advance as patients seek nonsurgical approaches to acute and chronic musculoskeletal injury and disease. However, academic acceptance as well as insurance reimbursement remain reliant on solid and repeatable positive results from large clinical trials. The authors summarize the evolution of PRP therapy and report on its status.

Regenerative principles enrich cardiac rehabilitation practice.

Cardiovascular morbidity imposes a high degree of disability and mortality, with limited therapeutic options available in end-stage disease. Integral to standard of care, cardiac rehabilitation aims on improving quality-of-life and prolonging survival. The recent advent of regenerative technologies paves the way for a transformative era in rehabilitation medicine whereby, beyond controlling risk factors and disease progression, the prospect of curative solutions is increasingly tangible. To date, the spectrum of clinical experience in cardiac regenerative medicine relies on stem cell-based therapies delivered to the diseased myocardium either acutely/subacutely, after a coronary event, or in the setting of chronic heart failure. Application of autologous/allogeneic stem cell platforms has established safety and feasibility, with encouraging signals of efficacy. Newer protocols aim to purify cell populations in an attempt to eliminate nonregenerative and enrich for regenerative cell types before use. Most advanced technologies have been developed to isolate resident cell populations directly from the heart or, alternatively, condition cells from noncardiac sources to attain a disease-targeted lineage-specified phenotype for optimized outcome. Because a multiplicity of cell-based technologies has undergone phase I/II evaluation, pivotal trials are currently underway in larger patient populations. Translation of regenerative principles into clinical practice will increasingly involve rehabilitation providers across the continuum of patient care. Regenerative rehabilitation is thus an emerging multidisciplinary field, full of opportunities and ready to be explored.

Regenerative medicine: transforming the drug discovery and development paradigm.

Despite the explosion of knowledge in basic biological processes controlling tissue regeneration and the growing interest in repairing/replacing diseased tissues and organs through various approaches (e.g., small and large molecule therapeutics, stem cell injection, tissue engineering), the pharmaceutical industry (pharma) has been reluctant to fully adopt these technologies into the traditional drug discovery and research and development (R&D) process. In this article, I discuss knowledge-base gaps and other possible factors that may delay full incorporation of these innovations in pharma R&D. I hope that this discussion will illuminate key issues that currently limit synergistic relationships between pharma and academic institutions and may even stimulate initiation of such collaborative research.

Utilization of stem cells to treat congenital heart disease: hype and hope.

PURPOSE OF REVIEW: Surgical advances over the past few decades have transformed the clinical management of congenital heart disease, such as hypoplastic left heart syndrome. Congenital heart disease affects more than 1% of liveborn infants and accounts for more than 2.5 million affected children per year worldwide. The cost and availability of complex medical management for these children becomes bluntly realized when heart failure progresses and only palliative options remain. Cell-based cardiac regeneration has been the focus of intensive efforts in adult heart disease for more than a decade and now has promise for pediatrics. RECENT FINDINGS: Innate cardiac regeneration in the pediatric setting is measurable and potentially modifiable in the early stages of development. Repurposing cell-based manufactured products to promote cardiac regeneration in congenital heart disease has demonstrated significant improvement in cases of dilated cardiomyopathy and structural heart disease in infants. SUMMARY: A focus on preemptive cardiac regeneration in the pediatric setting may offer new insights into the timing of surgery, location of cell-based delivery, and type of cell-based regeneration that could further inform acquired cardiac disease applications. The concept of cell-based pediatric cardiac regenerative surgery could transform the management of congenital heart disease when cost-effective strategies produce a valuable adjunctive solution to improve outcomes of cardiac surgery.