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

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

Trapping metastatic cancer cells with mechanical ratchet arrays

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.actbio.2023.08.034.Current treatments for cancer, such as chemotherapy, radiotherapy, immunotherapy, and surgery, have positive results but are generally ineffective against metastatic tumors. Treatment effectiveness can be improved by employing bioengineered cancer traps, typically utilizing chemoattractant-loaded materials, to attract infiltrating cancer cells preventing their uncontrolled spread and potentially enabling eradication. However, the encapsulated chemical compounds can have adverse effects on other cells causing unwanted responses, and the generated gradients can evolve unpredictably. Here, we report the development of a cancer trap based on mechanical ratchet structures to capture metastatic cells. The traps use an array of asymmetric local features to mechanically attract cancer cells and direct their migration for prolonged periods. The trapping efficiency was found to be greater than isotropic or inverse anisotropic ratchet structures on either disseminating cancer cells and tumor spheroids. Importantly, the traps exhibited a reduced effectiveness when targeting non-metastatic and non-tumorigenic cells, underscoring their particular suitability for capturing highly invasive cancer cells. Overall, this original approach may have therapeutic implications for fighting cancer, and may also be used to control cell motility for other biological processes.This research was funded by the Portuguese Foundation for Science and Technology (FCT) under the program CEEC Individual 2017 (CEECIND/00352/2017) and IC&DT (2022.02260.PTDC)

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.)

Advanced multifunctional wound dressing hydrogels as drug carriers

Skin injuries, especially chronic wounds, remain a significant healthcare system problem. The number of burns, diabetic patients, pressure ulcers, and other damages is also growing, particularly in elderly populations. Several investigations are pursued in designing more effective therapeutics for treating different wound injuries. These efforts have resulted in developing multifunctional wound dressings to improve wound repair. For this, preparing multifunctional dressings using various methods has provided a new attitude to support effective skin regeneration. This review focuses on the recent developments in designing multifunctional hydrogel dressings with hemostasis, adhesiveness, antibacterial, and antioxidant properties.This work was financially supported by Pasteur Institute of Iran (Grant No. 1256). S.C.K. is now the Research Coordinator of the University of Minho and has been the European Research Area Chair of the European Commission’s programme, FoReCaST and PTDC/BTM-ORG/28168/2017 of FCT, Portugal supported S.C.K

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