Biomimetic antibacterial pro-osteogenic cu-sericin MOFs for osteomyelitis treatment

Osteomyelitis is an inflammation of the bone caused by bacterial infection. It usually develops from broken bones, decayed teeth, or heavily punctured wounds. Multi-drug-resistant bacteria are the major hurdle in the treatment of osteomyelitis. The ever-rising antibiotic resistance even leads to amputations or fatalities as a consequence of chronic osteomyelitis. Hence, a single agent with antibacterial activity as well as bone regenerative properties can serve as a potential off-the-shelf product in the treatment of osteomyelitis. Herein, the antibacterial and pro-osteogenic characteristics of copper sericin (Cu-SER) metal–organic frameworks (MOFs) are reported. Sericin, a silk protein with antibacterial activity and an osteoinduction property, acts as an organic template for the deposition of Cu-SER MOFs, similar to collagen during biomineralization in bone. The MOFs exhibit cytocompatibility and osteogenic activity in a dose-dependent manner, as revealed by cell proliferation (alamarBlue) and mineralization (Alizarin Red S and Energy Dispersive X-ray analysis). The bactericidal activity of Cu-SER MOFs was investigated by scanning electron microscopy and a growth kinetic analysis. Together, the report illuminates the unique phenomenon of Cu-SER MOFs that kill bacteria upon contact while being well-tolerated by primary human cells. Hence, Cu-SER MOFs hold the potential to minimize antibiotic dependence.This work is supported by the European Union Framework Programme for Research and Innovation Horizon 2020 (No. 668983—FoReCaST) and the BREAST-IT project (PTDC/BTM-ORG/28168/2017) to S.C.K., funded by the Programa Operacional Regional do Norte supported by European Regional Development Funds (ERDF), Portugal

Photophysics of 2-(2' -hydroxyphenyl) benzoxazole in the presence of α-cyclodextrin: Deactivation of ESIPT through back protonation

55-58The complex photophysics of 2-(2'-hydroxyphenyl)- benzoxazole (HBO) in the presence of α-cyclodextrin (αCD) has been investigated using steady state as well as time-resolved spectroscopy. The 480 nm emission of HBO in aqueous medium has been found to be suppressed meaningfully in the presence of cyclodextrin. Steady state study as well as decay analyses suggest that the tautomer undergoes back protonation reaction in the excited state through the participation of αCD

Tissue engineering: from basic sciences to clinical perspectives

[Excerpt] Tissue engineering and regenerative medicine are interre-lated terms and go hand in hand whether we discuss aboutcells (of any kind especially stem and progenitor cells), bio-materials as matrices (2D films, 3D forms of scaffolds,nanofibers, hydrogels, nanoparticles, aerogel, microcapsules,mats, biogel for 3D printing, blends of naturals and/or syn-thetics, and others), and addition of bioactive molecules(delivery of growth hormones and drugs) for improvementand/or regeneration of tissues for biomedical applications (inrelation to cartilage, shin, bone, blood vessels, nerve conduits,cardiac, adipose, tissue expression, and others). Therefore,it includes basic principles of biological sciences, materialchemistry, and relevant engineering subjects. Finally formedical applications after proper clinical verifications of theappropriate films, scaffolds, devices, delivery systems, andother relevant products are needed. [...

Boosting the clinical translation of organ-on-a-chip technology

Organ-on-a-chip devices have become a viable option for investigating critical physiological events and responses; this technology has matured substantially, and many systems have been reported for disease modeling or drug screening over the last decade. Despite the wide acceptance in the academic community, their adoption by clinical end-users is still a non-accomplished promise. The reasons behind this difficulty can be very diverse but most likely are related to the lack of predictive power, physiological relevance, and reliability necessary for being utilized in the clinical area. In this Perspective, we briefly discuss the main attributes of organ-on-a-chip platforms in academia and how these characteristics impede their easy translation to the clinic. We also discuss how academia, in conjunction with the industry, can contribute to boosting their adoption by proposing novel design concepts, fabrication methods, processes, and manufacturing materials, improving their standardization and versatility, and simplifying their manipulation and reusability.This research was funded by the Portuguese Foundation for Science and Technology (FCT) under the program CEEC Individual 2017 (CEECIND/00352/2017) and the project 2MATCH (PTDC/BTM-ORG/28070/2017) funded by the Programa Operacional Regional do Norte supported by European Regional Development Funds (ERDF)

The biophysics of cell migration: biasing cell motion with feynman ratchets

The concepts and frameworks of soft matter physics and the laws of thermodynamics can be used to describe relevant developmental, physiologic, and pathologic events in which directed cell migration is involved, such as in cancer. Typically, this directionality has been associated with the presence of soluble long-range gradients of a chemoattractant, synergizing with many other guidance cues to direct the motion of cells. In particular, physical inputs have been shown to strongly influence cell locomotion. However, this type of cue has been less explored despite the importance in biology. In this paper, we describe recent in vitro works at the interface between physics and biology, showing how the motion of cells can be directed by using gradient-free environments with repeated local asymmetries. This rectification of cell migration, from random to directed, is a process reminiscent of the Feynman ratchet; therefore, this framework can be used to explain the mechanism behind directed cell motion.Portuguese Foundation for Science and Technology (FCT) under the program CEEC Individual 2017 (CEECIND/00352/2017). DC and SCK also acknowledge support from the FCT (project 2MATCH-02/SAICT/2017, no. 028070), funded by the Programa Operacional Regional do Norte supported by FEDER. Finally, all authors acknowledge financial support from the EU H2020 (FoReCaST, 668983). D. Riveline (IGBMC, Université de Strasbourg) and R. Voituriez (CNRS, UPMC) are acknowledged as former collaborators related to the main work describe

Cancer traps: implantable and on-chip solutions for early cancer detection and treatment

Cancer continues to be a major global health issue causing millions of deaths annually. While traditional therapeutic methods may be effective in many cases, they may not be suitable for highly metastatic cancers. Moreover, the late detection of tumors, when they have already spread and are harder to treat, further exacerbates the challenge in managing this disease. As a result, there is a growing interest in developing complementary tissue-engineered approaches for early cancer diagnosis and treatment to enhance patient recovery. Bioengineered cancer traps have gained significant attention due to their efficacy and ease of use. These trapping systems employ (bio)chemical and mechanical strategies to selectively capture and limit the spread of cancer cells, leading to their eradication from the body. Furthermore, when integrated into microfluidic devices, these cancer traps-on-a-chip can be used for liquid biopsy and the early detection of circulating tumor cells and other tumor-derived material, allowing for precision medicine treatments. Herein, this innovative approach to cancer theranostics, including its mechanism of action, current stage of development, and potential advantages and limitations is discussed.This work was supported by the Portuguese Foundation for Science and Technology (FCT) under the program CEEC Individual 2017 (CEECIND/00352/2017) and RECOVER IC&DT project (2022.02260.PTDC) attributed to D.

In vitro cancer models: a closer look at limitations on translation

In vitro cancer models are envisioned as high-throughput screening platforms for potential new therapeutic discovery and/or validation. They also serve as tools to achieve personalized treatment strategies or real-time monitoring of disease propagation, providing effective treatments to patients. To battle the fatality of metastatic cancers, the development and commercialization of predictive and robust preclinical in vitro cancer models are of urgent need. In the past decades, the translation of cancer research from 2D to 3D platforms and the development of diverse in vitro cancer models have been well elaborated in an enormous number of reviews. However, the meagre clinical success rate of cancer therapeutics urges the critical introspection of currently available preclinical platforms, including patents, to hasten the development of precision medicine and commercialization of in vitro cancer models. Hence, the present article critically reflects the difficulty of translating cancer therapeutics from discovery to adoption and commercialization in the light of in vitro cancer models as predictive tools. The state of the art of in vitro cancer models is discussed first, followed by identifying the limitations of bench-to-bedside transition. This review tries to establish compatibility between the current findings and obstacles and indicates future directions to accelerate the market penetration, considering the niche market.This work is supported by FROnTHERA (NORTE-01-0145-FEDER-000023) and the European Union Framework Programme for Research and Innovation Horizon 2020 under grant agreement No. 668983 —FoReCaST. N. Antunes thanks the funds provided by FCT under the doctoral program in Tissue Engineering, Regenerative Medicine and Stem Cells (PD/BD/143050/2018). SCK also records the support of FCT through the BREAST-IT project (PTDC/BTM-ORG/28168/2017)

AdipoSIGHT in therapeutic response: consequences in osteosarcoma treatment

Chemotherapeutic resistance is a major problem in effective cancer treatment. Cancer cells engage various cells or mechanisms to resist anti-cancer therapeutics, which results in metastasis and the recurrence of disease. Considering the cellular heterogeneity of cancer stroma, the involvement of stem cells is reported to affect the proliferation and metastasis of osteosarcoma. Hence, the duo (osteosarcoma: Saos 2 and human adipose-derived stem cells: ASCs) is co-cultured in present study to investigate the therapeutic response using a nonadherent, concave surface. Staining with a cell tracker allows real-time microscopic monitoring of the cell arrangement within the sphere. Cell–cell interaction is investigated by means of E-cadherin expression. Comparatively high expression of E-cadherin and compact organization is observed in heterotypic tumorspheres (Saos 2–ASCs) compared to homotypic ones (ASCs), limiting the infiltration of chemotherapeutic compound doxorubicin into the heterotypic tumorsphere, which in turn protects cells from the toxic effect of the chemotherapeutic. In addition, genes known to be associated with drug resistance, such as SOX2, OCT4, and CD44 are overexpressed in heterotypic tumorspheres post-chemotherapy, indicating that the duo collectively repels the effect of doxorubicin. The interaction between ASCs and Saos 2 in the present study points toward the growing oncological risk of using ASC-based regenerative therapy in cancer patients and warrants further investigation.This work is supported by the European Union Framework Programme for Research and Innovation Horizon 2020 (nº 668983 — FoReCaST; FROnTHERA—NORTE-01-0145-FEDER-000023), Investigator FCT program (IF/01214/2014—V.M.), FCT2015 (IF/01285/2015—J.M.O.) and PTDC/BTMORG/28168/2017 (V.B. and S.C.K.)

Tumor - stroma interactions alter the sensitivity of drug in breast cancer

Flat cell cultures or xenografts are inadequate tools to unravel cancer complex biology. 3D in vitro tumor models garnered interest since they recapitulate better dynamic mechanisms of cancer, but a gold standardmodel that faithfullymimics solid cancer is not available yet. 3D breast cancermodel is fabricated using freeze-dried silk fibroin scaffolds. Breast cancer cell lines (MCF-7 and MDA-MB231) are seeded with normal mammary fibroblasts onto silk fibroin scaffold (1 and 2mm thick). Cells proliferation is monitored by means of Alamar blue assay. 3D breast cancer models morphology is observed by confocal microscopy. Gene expression modulation concerning extracellular matrix markers is evaluated. Further, 3D bioengineered breast cancer models are treated with doxorubicin. Silk fibroin scaffolds allow the proliferation of cancer cells and fibroblasts. Cells growth is enhanced when cancer cells and fibroblasts are seeded together. Histological staining shows 3D cell organization. MMP-1, MMP-2, MMP-3, Col-1, and Fibronectin expression is upregulated in co-culture. After doxorubicin treatment, stronger reduction in cell activity is observed in 2mm SF scaffold in comparison to 1mm. The 3D in vitro breast cancer model obtained can easily be scaled-up and translated to the preclinical testing of novel chemotherapeutics.This work was supported by EU-Horizon 2020 grant FoReCaST—Forefront Research in 3D Disease Cancer Modelsasin vitroScreening Technologies (H2020-WIDESPREAD-2014-668983). The authors also acknowledge the FRONTHERA project (Frontiers of technology for theranostics of cancer,metabolic and neurodegenerative diseases) (NORTE-01-0145-FEDER-0000232) and Fundação Ciência e tecnologia (FCT grantagreement: PTDC/BTM-ORG/28168/2017 to VB and SK)

Smart responsive microneedles for controlled drug delivery

As an emerging technology, microneedles offer advantages such as painless administration, good biocompatibility, and ease of self-administration, so as to effectively treat various diseases, such as diabetes, wound repair, tumor treatment and so on. How to regulate the release behavior of loaded drugs in polymer microneedles is the core element of transdermal drug delivery. As an emerging on-demand drug-delivery technology, intelligent responsive microneedles can achieve local accurate release of drugs according to external stimuli or internal physiological environment changes. This review focuses on the research efforts in smart responsive polymer microneedles at home and abroad in recent years. It summarizes the response mechanisms based on various stimuli and their respective application scenarios. Utilizing innovative, responsive microneedle systems offers a convenient and precise targeted drug delivery method, holding significant research implications in transdermal drug administration. Safety and efficacy will remain the key areas of continuous efforts for research scholars in the future.This research was funded by College Nature Science Research Project of Jiangsu Province, China (Grant No. 20KJA540002) and Postgraduate Research & Practice Innovation Program of Jiangsu Province, China (Grant No. KYCX23-3257