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Skeletal disorders pose significant challenges to health and quality of life, underscoring the critical need for innovative bone repair methods. Recent studies have spotlighted the promising role of extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (BMSCs) in conjunction with biomimetic peptide (BP) WKYMVm (WK) for bone repair. This research leveraged a self-healing hydrogel as a carrier, effectively loading EVs and WK to enhance treatment efficacy. Through the regulation of vascular formation and osteoblast differentiation, notable advancements were achieved in mending femoral defect bone injuries, offering new possibilities for addressing bone metabolic disorders. The detailed methodology encompassed hydrogel preparation, EVs and WK loading, in vitro cell studies, and rat model experiments. Results unveiled that graphene oxide gelatin hydrogel loaded with wkymvm and extracellular vesicles (GOG@WK-EVs) notably bolstered osteogenic differentiation of bone cells and angiogenesis, while impeding osteoclast differentiation, culminating in potent bone regeneration within femoral defects. [ABSTRACT FROM AUTHOR]

The increasing demand for effective cosmetics has driven the development of innovative analytical techniques to ensure product quality. This work presents the development and validation of a zwitterionic hydrophilic interaction liquid chromatography method, coupled with ultraviolet detection, for the quantification of copper tripeptide in cosmetics. A novel protocol for sample preparation was developed using fabric phase sorptive extraction to extract the targeted analyte from the complex cosmetic cream matrix, followed by chromatographic separation on a ZIC®-pHILIC analytical column. A thorough investigation of the chromatographic behavior of the copper tripeptide on the HILIC column was performed during method development. The mobile phase consisted of 133 mM ammonium formate (pH 9, adjusted with ammonium hydroxide) and acetonitrile at a 40:60 (v/v) ratio, with a flow rate of 0.2 mL/min. A design of experiments (DOE) approach allowed precise adjustments to various factors influencing the extraction process, leading to the optimization of the fabric phase sorptive extraction protocol for copper tripeptide analysis. The method demonstrated excellent linearity over a concentration range of 0.002 to 0.005% w/w for copper tripeptide, with a correlation coefficient exceeding 0.998. The limits of detection and quantitation were 5.3 × 10−4% w/w and 2.0 × 10−3% w/w, respectively. The selectivity of the method was verified through successful separation of copper tripeptide from other cream components within 10 min, establishing its suitability for high-throughput quality control of cosmetic formulations. [ABSTRACT FROM AUTHOR]

Beauty and personal care became a significant part of the global economy for two reasons: (1) The elderly growing in the global population and (2) the desire of women and men to appear younger and more attractive. Thus, both young and old people are looking for revolutionary nutritional eco-cosmetics (combined use of cosmeceuticals and nutraceuticals) manufactured by natural active ingredients, using biopolymers as substrates, and made by innovative and sustainable technologies. Consequently, the market of both cosmetics and diet supplements is continually growing together with the request of natural active ingredients, including bio-peptides and biological macromolecules such as chitin and lignin. Therefore, both consumers and industry need to recover innovative active ingredients and carriers (vehicles), naturally derived and supported by advanced methods for controlling their effectiveness and safeness on skin and mucous membrane layers. The use of selected bio-ingredients, such as hyaluronic acid and bio-mimetic peptides, obtained by advanced, innovative and sustainable bio nanotechnologies, will be of interest to develop smart cosmeceutical and nutraceutical formulations. Innovation is considered the key business strategy to drive sustainable economic growth. For trying to reduce waste and produce sustainable, biodegradable and innovative products, the realization of new non-woven tissues, used as carriers for making innovative cosmeceuticals and nutraceuticals was considered. Both carriers and active ingredients have been obtained from food waste to reduce loss and pollution. This review will report a brief description of the skin functions, trying also to focus and discuss some of the active ingredients and carriers used in nutritional eco-cosmetics to clarify the supposed mechanism of action, effectiveness and safeness of both active ingredients and carriers, as well as the supposed activity of beauty and personal care products.

Mimicking bone extracellular matrix (ECM) is paramount to develop novel biomaterials for bone tissue engineering. In this regard, the combination of integrin-binding ligands together with osteogenic peptides represents a powerful approach to recapitulate the healing microenvironment of bone. In the present work, we designed polyethylene glycol (PEG)-based hydrogels functionalized with cell instructive multifunctional biomimetic peptides (either with cyclic RGD-DWIVA or cyclic RGD-cyclic DWIVA) and cross-linked with matrix metalloproteinases (MMPs)-degradable sequences to enable dynamic enzymatic biodegradation and cell spreading and differentiation. The analysis of the intrinsic properties of the hydrogel revealed relevant mechanical properties, porosity, swelling and degradability to engineer hydrogels for bone tissue engineering. Moreover, the engineered hydrogels were able to promote human mesenchymal stem cells (MSCs) spreading and significantly improve their osteogenic differentiation. Thus, these novel hydrogels could be a promising candidate for applications in bone tissue engineering, such as acellular systems to be implanted and regenerate bone or in stem cells therapy.

Beauty and personal care became a significant part of the global economy for two reasons: (1) The elderly growing in the global population and (2) the desire of women and men to appear younger and more attractive. Thus, both young and old people are looking for revolutionary nutritional eco-cosmetics (combined use of cosmeceuticals and nutraceuticals) manufactured by natural active ingredients, using biopolymers as substrates, and made by innovative and sustainable technologies. Consequently, the market of both cosmetics and diet supplements is continually growing together with the request of natural active ingredients, including bio-peptides and biological macromolecules such as chitin and lignin. Therefore, both consumers and industry need to recover innovative active ingredients and carriers (vehicles), naturally derived and supported by advanced methods for controlling their effectiveness and safeness on skin and mucous membrane layers. The use of selected bio-ingredients, such as hyaluronic acid and bio-mimetic peptides, obtained by advanced, innovative and sustainable bio nanotechnologies, will be of interest to develop smart cosmeceutical and nutraceutical formulations. Innovation is considered the key business strategy to drive sustainable economic growth. For trying to reduce waste and produce sustainable, biodegradable and innovative products, the realization of new non-woven tissues, used as carriers for making innovative cosmeceuticals and nutraceuticals was considered. Both carriers and active ingredients have been obtained from food waste to reduce loss and pollution. This review will report a brief description of the skin functions, trying also to focus and discuss some of the active ingredients and carriers used in nutritional eco-cosmetics to clarify the supposed mechanism of action, effectiveness and safeness of both active ingredients and carriers, as well as the supposed activity of beauty and personal care products. [ABSTRACT FROM AUTHOR]

Alopecia as a disease condition can be a symptom of other ailments, the body’s reaction to medications, hormonal changes, nutritional deficiencies, hygiene negligence, too intense or frequent cosmetic procedures, or it can constitute an independent disease syndrome. Depending on the individual genetic traits, alopecia may also be inherited. Usually, there is no one universal cause for this disease to occur. Properly conducted diagnosis of the problem and individually selected therapeutic substances can help to deal with this problem or at least delay hair loss associated with the physiological aging process. One of the treatments that are used to support the treatment or prevention of alopecia is needle mesotherapy. It is a local treatment that delivers healing substances having stimulating, regenerating, and nourishing effects directly to the skin or hair follicles. The medicinal substances administered during the needle mesotherapy treatment include peptides, biotin, minoxidil, d-panthenol, vitamins, and minerals, alone or in the form of mixtures, as well as platelet-rich plasma and stem cells. The effects of needle mesotherapy in alopecia are visible after a single treatment when hair loss stops. On the other hand, the thickening and regrowth of new hair are visible after a series of treatments. The full course of therapy depends on the type of alopecia, a patient’s condition, and its comorbidities. It usually consists of four to eight treatments performed at two-week intervals. In the case of alopecia, they are visible after two months, and to maintain the effect, a reminder treatment is recommended after six months. Not all people can undergo such a procedure. The main contraindications include: (1) pregnant and lactating women; (2) children and persons under the age of 18; (3) people who are allergic to any of the ingredients of the administered preparation; (4) people with skin lesions, skin diseases, active infections (bacterial, viral, fungal) or susceptibility to streptococcal infections (recurrent strep throat); (5) people taking drugs: immunosuppressants, anticoagulants, non-steroidal anti-inflammatory drugs, high doses of glucocorticosteroids; (6) patients with decompensated diabetes, neoplastic, mental, rheumatic diseases, or other autoimmune disorders. Needle mesotherapy is very popular in cosmetology and aesthetic medicine clinics. This innovative method is a proven and relatively safe procedure in the fight against various skin conditions, including alopecia. Keywords: excessive hair loss, alopecia, needle mesotherapy, platelet-rich plasma, biomimetic peptides, stem cells.

Drug-loaded pH-responsive nanoparticles are potential drug carriers in nanotherapeutics delivery because they can remain stable in normal tissues but can disassemble and release drug molecules in tumors. In this study, the mechanisms of self-assembly and disassembly were investigated by analyzing the characteristics of three kinds of biomimetic peptides with different components and sequences. The structural parameters and energy changes during self-assembly and disassembly were calculated by molecular dynamics simulation. Transmission electron microscopy, Fourier transform infrared spectroscopy, and atomic force microscopy were used to observe morphological changes and measure the strength of hydrophobic and hydrophilic interactions between peptides. Results show that the hydrophobic and hydrophilic interactions play crucial roles in the self-assembly and disassembly processes of peptides. The structure of the peptide clusters after self-assembly became tighter as the difference between hydrophobic and hydrophilic interactions increased, whereas a decrease in this difference led to the increased disassembly of the peptides. In general, polyethylene glycol chain modification was necessary in disassembly, and peptides with straight structures had stronger disassembly ability than that with branched structures with the same components. The morphology of peptide clusters can be controlled under different pH values by changing the composition and structure of the peptides for enhanced drug retention and sustained release. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Introduction Alopecia areata (AA), also known as ‘area Celsi’, is the second most common form of hair loss affecting the scalp. Newly proposed treatments for AA include low-level light therapy, biologics such as Janus kinase inhibitors and autologous platelet-rich plasma (PRP), which is a well-known “elixir” for hair growth. Bioactive peptides developed through biotechnological applications have been used to overcome the limitations of PRP. More recently, the involvement of microbiota in hair growth disorders, in AA in particular, has been reported, and the usefulness of microbial metabolites, i.e. postbiotics, has been suggested. Methods This study was a randomized double-blinded parallel-group study in which 160 persons of both sexes affected by AA and aged between 18 and 60 years were enrolled. The subjects were randomly assigned to a treatment group (group 1), receiving the TR-PRP plus-Celsi cosmetic product, and a placebo group (group 2). The SALT (Severity of Alopecia Tool) score was determined in both groups at baseline and after 2 and 3 months of treatment, and the results compared between groups. Results The subjects in group 1 showed a significant change from baseline in SALT score at 2 months of treatment (61.04% ± 3.45%; p

Introduction: Alopecia areata (AA), also known as 'area Celsi', is the second most common form of hair loss affecting the scalp. Newly proposed treatments for AA include low-level light therapy, biologics such as Janus kinase inhibitors and autologous platelet-rich plasma (PRP), which is a well-known "elixir" for hair growth. Bioactive peptides developed through biotechnological applications have been used to overcome the limitations of PRP. More recently, the involvement of microbiota in hair growth disorders, in AA in particular, has been reported, and the usefulness of microbial metabolites, i.e. postbiotics, has been suggested. Methods: This study was a randomized double-blinded parallel-group study in which 160 persons of both sexes affected by AA and aged between 18 and 60 years were enrolled. The subjects were randomly assigned to a treatment group (group 1), receiving the TR-PRP plus-Celsi cosmetic product, and a placebo group (group 2). The SALT (Severity of Alopecia Tool) score was determined in both groups at baseline and after 2 and 3 months of treatment, and the results compared between groups. Results: The subjects in group 1 showed a significant change from baseline in SALT score at 2 months of treatment (61.04% ± 3.45%; p < 0.0001), with a further improvement at the end of treatment (3 months) (69.56% ± 4.32%; p < 0.0001). No significant changes from baseline were reported for the subjects in group 2 (T1: 26.45% ± 3.64%; T3: 27.63% ± 7.61%). Conclusions: The results of this study provide further proof of the efficacy of bioactive peptides that mimick the growth factors present in PRP in subjects affected by AA. They also add to our knowledge of the link between microbiota and hair growth disorders, emphasizing the importance of studies on the microbial community and microbial metabolites as a novel therapeutic approach. [ABSTRACT FROM AUTHOR]

Scope. To determine the therapeutic potency of telogen effluvium complex therapy and androgenetic alopecia. Materials and methods. There are presented results on treatment of 45 patients with telogen hair loss (15 women) and androgenetic alopecia (15 men and 15 women) who were divided into two groups depending on the method of treatment: the main group and the control group. Patients of the main group got pharmaceutical treatment (homeopathic medicine, a L-cysteine + B vitamins preparation) and local therapy (biomimetic peptides-based lotion on the skin of the hairy part of head). The patients in the control group received a similar pharmaceutical treatment but with no applying of biomimetic peptide lotion to the skin of the hairy part of head (scalp). Before and after the therapy the computer-assisted hair and scalp diagnostics were conducted to the fixed zones with permanent marks. The overview photographs of the scalp before the treatment and at follow-up visits were made for the purpose of the follow-up clinical performance evaluation. Results. The computer-assisted hair and scalp diagnostics results analysis of the patients in the study and control groups proved the complex alopecia treatment to be effective.

Background: Alopecia areata (AA) is a non-scarring auto-immune hair disorder. Recent researches explained the role of growth factors (GFs) in hair follicle cycling. The main reservoir of GFs are alpha-granules of platelets and novel procedures have been implemented aimed at collecting platelet-rich plasma (PRP). PRP has been safely implemented in many medical applications and has also been successfully used as alternative cell-based therapy for the treatment of hair growth disorders, among which also AA. Objectives: By means of a randomized double-blinded, placebo and active-controlled, parallel group study we have studied the efficacy of a cosmetic product (named TR-M-PRP plus) comprising biomimetic peptides specific for hair growth, mimicking PRP composition for the treatment of AA. Subjects were treated for three months and evaluated, at the end of the study and after one month of follow-up, as regards hair growth using SALT score. Results: TR-M-PRP plus-like topic produced a statistically significant (p <.001) clinical improvement in SALT score after 3 months of therapy, compared to baseline. Hair growth results further improved after 1 month of follow-up. Conclusions: This clinical investigation suggests that the biotechnological designed PRP-like cosmetic could represent a valid and safer alternative to autologous PRP for the treatment of AA. [ABSTRACT FROM AUTHOR]

The inclusion of biofunctional molecules with synthetic bone graft substitutes has the potential to enhance tissue regeneration during treatment of traumatic bone injuries. The clinical use of growth factors has though been associated with complications, some serious. The use of smaller, active peptides has the potential to overcome these problems and provide a cost-effective, safe route for the manufacture of enhanced bone graft substitutes. This review considers the design of peptide-enhanced bone graft substitutes, and how peptide selection and attachment method determine clinical efficacy. It was determined that covalent attachment may reduce the known risks associated with growth factor-loaded bone graft substitutes, providing a predictable tissue response and greater clinical efficacy. Peptide choice was found to be critical, but even within recognised families of biologically active peptides, the configurations that appeared to most closely mimic the biological molecules involved in natural bone healing processes were most potent. It was concluded that rational, evidence-based design of peptide-enhanced bone graft substitutes offers a pathway to clinical maturity in this highly promising field.

Zarema I Gazitaeva,1 Anna O Drobintseva,2 Yongji Chung,3 Victoria O Polyakova,2 Igor M Kvetnoy2 1Institute of Beauty Fijie, Moscow, 2Department of Pathomorphology, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint-Petersburg, Russian Federation; 3Caregen Co., Ltd. Research Center, Seoul, South Korea Background: Biomimetic peptides are synthetic compounds that are identical to amino acid sequence synthesized by an organism and can interact with growth factor receptors and provide antiaging clinical effects.Purpose: The purpose of this study was to investigate the effects of biomimetic peptides on the repair processes in the dermis using a model of cell cultures and in vivo.Patients and methods: Five female volunteers were subjected to the injection of biomimetic peptides 1 month prior to the abdominoplasty procedure. Cell culture, immunocytochemistry, and confocal microscopy methods were used in this study.Results: Biomimetic peptides regulate the synthesis of proteins Ki-67, type I procollagen, AP-1, and SIRT6 in cell cultures of human fibroblasts. They contribute to the activation of regeneration processes and initiation of mechanisms that prevent aging. Intradermal administration of complex of biomimetic peptides produces a more dense arrangement of collagen fibers in the dermis and increased size of the fibers after 2 weeks. The complex of biomimetic peptides was effective in the in vivo experiments, where an increase in the proliferative and synthetic activities of fibroblasts was observed.Conclusion: This investigation showed that the studied peptides have biological effects, testifying the stimulation of reparative processes in the skin under their control. Keywords: biomimetic peptides, skin aging, collagen, reparation processes, mesotherapy

Sensitive skin is a frequently mentioned cosmetic complaint. Addition of a biomimetic of neuromediator has recently appeared as a promising new way to cure skin care product problems. This study was aimed to assess the inhibitory effect of a biomimetic lipopeptide derived from proopiomelanocortin (bPOMC) on capsaicin-induced sensory irritation in human volunteers and also to compare its protective effect with that of the well-known anti irritant strontium chloride. The effect of each test compound was studied on 28 selected healthy volunteers with sensitive skin in accordance with a double-blind vehicle-controlled protocol. From day 1 to day 13 each group was applied the test compound (bPOMC or strontium chloride) to one wing of the nose and the corresponding placebo (vehicle) to the other side twice daily. On days 0 and 14, acute skin irritation was induced by capsaicin solution and quantified using clinical stinging test assessments. Following the application of capsaicin solution, sensory irritation was evaluated using a 4-point numeric scale. The sensations perceived before and after treatment (on days 0 and 14) was calculated for the two zones (test materials and vehicle). Ultimately the percentage of variation between each sample and the placebo and also the inhibitory effect of bPOMC compared to that of strontium chloride were reported. Clinical results showed that after two weeks treatment, the levels of skin comfort reported in the group treated with bPOMC were significantly higher than those obtained in the placebo group and the inhibitory effect of bPOMC was about 47% higher than that of strontium chloride. The results of the present study support the hypothesis that biomimetic peptides may be effective on sensitive skin.

Molecular signals in the form of growth factors are the main modulators of cell behavior. However, the use of growth factors in tissue engineering has several drawbacks, including their costs, difficult production, immunogenicity and short half-life. Furthermore, many of them are pleiotropic and, since a single growth factor can have different active domains, their effect is not always fully controllable. A very interesting alternative that has recently emerged is the use of biomimetic peptides. Sequences derived from the active domains of soluble or extracellular matrix proteins can be used to functionalize the biomaterials used as scaffolds for new tissue growth to either direct the attachment of cells or to be released as soluble ligands. Since these short peptides can be easily designed and cost-effectively synthesized in vitro , their use has opened up a world of new opportunities to obtain cheaper and more effective implants for regenerative medicine strategies. In this extensive review we will go through many of the most important peptides with potential interest for bone tissue engineering, not limiting to those that only mediate cell adhesion or induce the osteogenic differentiation of progenitor cells, but also focusing on those that direct angiogenesis because of its close relation with bone formation. [ABSTRACT FROM AUTHOR]

Sensitive skin is a frequently mentioned cosmetic complaint. Addition of a biomimetic of neuromediator has recently appeared as a promising new way to cure skin care product problems. This study was aimed to assess the inhibitory effect of a biomimetic lipopeptide derived from proopiomelanocortin (bPOMC) on capsaicin-induced sensory irritation in human volunteers and also to compare its protective effect with that of the well-known anti irritant strontium chloride. The effect of each test compound was studied on 28 selected healthy volunteers with sensitive skin in accordance with a double-blind vehicle-controlled protocol. From day 1 to day 13 each group was applied the test compound (bPOMC or strontium chloride) to one wing of the nose and the corresponding placebo (vehicle) to the other side twice daily. On days 0 and 14, acute skin irritation was induced by capsaicin solution and quantified using clinical stinging test assessments. Following the application of capsaicin solution, sensory irritation was evaluated using a 4-point numeric scale. The sensations perceived before and after treatment (on days 0 and 14) was calculated for the two zones (test materials and vehicle). Ultimately the percentage of variation between each sample and the placebo and also the inhibitory effect of bPOMC compared to that of strontium chloride were reported. Clinical results showed that after two weeks treatment, the levels of skin comfort reported in the group treated with bPOMC were significantly higher than those obtained in the placebo group and the inhibitory effect of bPOMC was about 47% higher than that of strontium chloride. The results of the present study support the hypothesis that biomimetic peptides may be effective on sensitive skin. [ABSTRACT FROM AUTHOR]

Aim: We aimed to set up a self-standing, biomimetic scaffold system able to induce and support per se neuronal differentiation of autologous multipotent cells. Materials & methods: We isolated a population of human circulating multipotent cells (hCMCs), and used carbon nanotube/polymer nanocomposite scaffolds to mimic electrical/nanotopographical features of the neural environment, and biomimetic peptides reproducing axon guidance cues from neural proteins. Results: hCMCs showed high degree of stemness and multidifferentiative potential; stimuli from the scaffolds and biomimetic peptides could induce and boost hCMC differentiation toward neuronal lineage despite the absence of exogenously added, specific growth factors. Conclusion: This work suggests the scaffold-peptides system combined with autologous hCMCs as a functional biomimetic, self-standing prototype for neural regenerative medicine applications. [ABSTRACT FROM AUTHOR]

Carbon nanotubes are attractive candidates for the development of scaffolds able to support neuronal growth and differentiation thanks to their ability to conduct electrical stimuli, to interface with cells and to mimic the neural environment. We developed a biocompatible composite scaffold, consisting of multi-walled carbon nanotubes dispersed in a poly- l -lactic acid matrix able to support growth and differentiation of human neuronal cells. Moreover, to mimic guidance cues from the neural environment, we also designed synthetic peptides, derived from L1 and LINGO1 proteins. Such peptides could positively modulate neuronal differentiation, which is synergistically improved by the combination of the nanocomposite scaffold and the peptides, thus suggesting a prototype for the development of implants for long-term neuronal growth and differentiation. From the Clinical Editor The study describes the design and preparation of nanocomposite scaffolds with multi-walled carbon nanotubes in a poly-L-lactic acid matrix. This compound used in combination with peptides leads to synergistic effects in supporting neuronal cell growth and differentiation. [ABSTRACT FROM AUTHOR]

Cell-material interactions are regulated by mimicking bone extracellular matrix on the surface of biomaterials. In this regard, reproducing the extracellular conditions that promote integrin and growth factor (GF) signaling is a major goal to trigger bone regeneration. Thus, the use of synthetic osteogenic domains derived from bone morphogenetic protein 2 (BMP-2) is gaining increasing attention, as this strategy is devoid of the clinical risks associated with this molecule. In this work, the wrist and knuckle epitopes of BMP-2 are screened to identify peptides with potential osteogenic properties. The most active sequences (the DWIVA motif and its cyclic version) are combined with the cell adhesive RGD peptide (linear and cyclic variants), to produce tailor-made biomimetic peptides presenting the bioactive cues in a chemically and geometrically defined manner. Such multifunctional peptides are next used to functionalize titanium surfaces. Biological characterization with mesenchymal stem cells demonstrates the ability of the biointerfaces to synergistically enhance cell adhesion and osteogenic differentiation. Furthermore, in vivo studies in rat calvarial defects prove the capacity of the biomimetic coatings to improve new bone formation and reduce fibrous tissue thickness. These results highlight the potential of mimicking integrin-GF signaling with synthetic peptides, without the need for exogenous GFs., (© 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

As a promising 2D nanocarrier, the biggest challenge of bare black phosphorus nanosheets (BP NSs) lies in the inherent instability, while it can be improved by surface modification strategies to a great extent. Considering the existing infirm BP NSs surface modification strategies, A mussels-inspired strong adhesive biomimetic peptide with azide groups for surface modification to increase the stability of BP NSs is synthesized. The azide groups on the peptide can quickly and precisely bind to the targeting ligand through click chemistry, solving the problem of nonspecificity of secondary modification of other mussel-mimicking materials. Besides, a catechol-Gd 3+ coordination network is further constructed for magnetic resonance imaging (MRI) and inducing intracellular endo/lysosome escape. The fabricated BP-DOX@Gd/(DOPA) 4 -PEG-TL nanoplatform exhibits enhanced antitumor abilities through synergetic chemo/photothermal effects both in vitro and in vivo., (© 2022 Wiley-VCH GmbH.)

The presentation of development-relevant bioactive cues by biomaterial scaffolds is essential to the guided differentiation of seeded human mesenchymal stem cells (hMSCs) and subsequent tissue regeneration. Wnt5a is a critical non-canonical Wnt signaling ligand and plays a key role in the development of musculoskeletal tissues including cartilage. Herein we investigate the efficacy of biofunctionalizing the hyaluronic acid hydrogel with a synthetic Wnt5a mimetic ligand (Foxy5 peptide) to promote the chondrogenesis of hMSCs and the potential underlying molecular mechanism. Our findings show that the conjugation of Foxy5 peptide in the hydrogels activates non-canonical Wnt signaling of encapsulated hMSCs via the upregulation expression of PLCE1, CaMKII-β , and downstream NFATc1 , leading to enhanced expression of chondrogenic markers such as SOX9. The decoration of Foxy5 peptide also promotes the metabolic activities of encapsulated hMSCs as evidenced by upregulated gene expression of mitochondrial complex components and glucose metabolism biomarkers, leading to enhanced ATP biosynthesis. Furthermore, the conjugation of Foxy5 peptide activates the non-canonical Wnt, PI3K-PDK-AKT and IKK/NF-κB signaling pathways, thereby inhibiting the hypertrophy of the chondrogenically induced hMSCs in the hydrogels under both in vitro and in vivo conditions. This enhanced chondrogenesis and attenuated hypertrophy of hMSCs by the biomaterial-mediated bioactive cue presentation facilitates the potential clinical translation of hMSCs for cartilage regeneration. Our work provides valuable guidance to the rational design of bio-inductive scaffolds for various applications in regenerative medicine. [Display omitted] [ABSTRACT FROM AUTHOR]

The inclusion of biofunctional molecules with synthetic bone graft substitutes has the potential to enhance tissue regeneration during treatment of traumatic bone injuries. The clinical use of growth factors has though been associated with complications, some serious. The use of smaller, active peptides has the potential to overcome these problems and provide a cost-effective, safe route for the manufacture of enhanced bone graft substitutes. This review considers the design of peptide-enhanced bone graft substitutes, and how peptide selection and attachment method determine clinical efficacy. It was determined that covalent attachment may reduce the known risks associated with growth factor-loaded bone graft substitutes, providing a predictable tissue response and greater clinical efficacy. Peptide choice was found to be critical, but even within recognised families of biologically active peptides, the configurations that appeared to most closely mimic the biological molecules involved in natural bone healing processes were most potent. It was concluded that rational, evidence-based design of peptide-enhanced bone graft substitutes offers a pathway to clinical maturity in this highly promising field. [ABSTRACT FROM AUTHOR]

Protein-based self-assembling hydrogels can exhibit remarkably tunable properties as a scaffold for regenerative medicine applications. In this study, we sought to develop a leucine zipper (LZ) based self-assembling hydrogel with function-specific motifs for tissue-specific regeneration. As a proof-of-concept approach, we incorporated (a) calcium-binding domains ESQES and QESQSEQS derived from dentin matrix protein 1 (DMP1) and (b) an heparin-binding domain adjacent preceded by an MMP2 (matrix metalloprotease 2) cleavage site to facilitate loading of heparin binding growth factors, such as BMP-2, VEGF, and TGF-β1, and their release in vivo by endogenous MMP2 proteolytic cleavage. These scaffolds were characterized and evaluated in vitro and in vivo. In vivo studies highlighted the potential of the engineered LZ hydrogel with respect to osteogenic differentiation of stem cells. The premineralized LZ scaffold loaded with HMSCs showed an enhanced osteoinductive property when compared with the control nonmineralized scaffold. The LZ backbone with heparin-binding domain containing an MMP2 cleavage site facilitated tethering of heparin-binding growth factors, such as VEGF, TGF-β1 and BMP2 and demonstrated controlled release of these active growth factor both in vitro and in vivo and demonstrated growth factor specific activity in vivo (BMP-2 and TGF-β1). Overall, we present a versatile protein based self-assembling system with tunable properties for tissue regeneration.

Cancer remains one of the leading causes of death worldwide, indicating that current cancer therapies are ineffective. Therefore, new treatments with high specificity and low toxicity are needed. Cancerous cells can be distinguished from normal cells based on expression of key proteins, namely surface proteins, scaffold proteins and signaling molecules. Moreover, cancer cells communicate with the tumor microenvironment consisting of a heterogenous population of cells, extracellular matrix components and soluble factors such as cytokines/chemokines and growth factors. Most therapeutic interventions have been designed to specifically target these proteins of interest. Biomimetic peptides (BPs) are artificially designed peptides that imitate the action of parent proteins or peptides. BPs can be classified into at least three types based on their target molecule: BPs that target (i) cell-surface molecules, (ii) intracellular molecules, and (iii) cancer cell-tumor microenvironment interactions. In this review, we analyze/discuss the current strategies for targeting tumors using BPs., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)