Implantable SDF-1α-loaded silk fibroin hyaluronic acid aerogel sponges as an instructive component of the glioblastoma ecosystem: Between chemoattraction and tumor shaping into resection cavities.

In view of inevitable recurrences despite resection, glioblastoma (GB) is still an unmet clinical need. Dealing with the stromal-cell derived factor 1-alpha (SDF-1α)/CXCR4 axis as a hallmark of infiltrative GB tumors and with the resection cavity situation, the present study described the effects and relevance of a new engineered micro-nanostructured SF-HA-Hep aerogel sponges, made of silk fibroin (SF), hyaluronic acid (HA) and heparin (Hep) and loaded with SDF-1α, to interfere with the GB ecosystem and residual GB cells, attracting and confining them in a controlled area before elimination. 70 µm-pore sponges were designed as an implantable scaffold to trap GB cells. They presented shape memory and fit brain cavities. Histological results after implantation in brain immunocompetent Fischer rats revealed that SF-HA-Hep sponges are well tolerated for more than 3 months while moderately and reversibly colonized by immuno-inflammatory cells. The use of human U87MG GB cells overexpressing the CXCR4 receptor (U87MG-CXCR4+) and responding to SDF-1α allowed demonstrating directional GB cell attraction and colonization of the device in vitro and in vivo in orthotopic resection cavities in Nude rats. Not modifying global survival, aerogel sponge implantation strongly shaped U87MG-CXCR4+ tumors in cavities in contrast to random infiltrative growth in controls. Overall, those results support the interest of SF-HA-Hep sponges as modifiers of the GB ecosystem dynamics acting as "cell meeting rooms" and biocompatible niches whose properties deserve to be considered toward the development of new clinical procedures. STATEMENT OF SIGNIFICANCE: Brain tumor glioblastoma (GB) is one of the worst unmet clinical needs. To prevent the relapse in the resection cavity situation, new implantable biopolymer aerogel sponges loaded with a chemoattractant molecule were designed and preclinically tested as a prototype targeting the interaction between the initial tumor location and its attraction by the peritumoral environment. While not modifying global survival, biocompatible SDF1-loaded hyaluronic acid and silk fibroin sponges induce directional GB cell attraction and colonization in vitro and in rats in vivo. Interestingly, they strongly shaped GB tumors in contrast to random infiltrative growth in controls. These results provide original findings on application of exogenous engineered niches that shape tumors and serve as cell meeting rooms for further clinical developments.

Insights into Healthcare Professionals' Perceptions and Attitudes toward Nanotechnological Device Application: What Is the Current Situation in Glioblastoma Research?

Nanotechnology application in cancer treatment is promising and is likely to quickly spread worldwide in the near future. To date, most scientific studies on nanomaterial development have focused on deepening the attitudes of end users and experts, leaving clinical practice implications unexplored. Neuro-oncology might be a promising field for the application of nanotechnologies, especially for malignant brain tumors with a low-survival rate such as glioblastoma (GBM). As to improving patients' quality of life and life expectancy, innovative treatments are worth being explored. Indeed, it is important to explore clinicians' intention to use experimental technologies in clinical practice. In the present study, we conducted an exploratory review of the literature about healthcare workers' knowledge and personal opinions toward nanomedicine. Our search (i) gives evidence for disagreement between self-reported and factual knowledge about nanomedicine and (ii) suggests the internet and television as main sources of information about current trends in nanomedicine applications, over scientific journals and formal education. Current models of risk assessment suggest time-saving cognitive and affective shortcuts, i.e., heuristics support both laypeople and experts in the decision-making process under uncertainty, whereas they might be a source of error. Whether the knowledge is poor, heuristics are more likely to occur and thus clinicians' opinions and perspectives toward new technologies might be biased.

Physical stimuli-emitting scaffolds: The role of piezoelectricity in tissue regeneration.

The imbalance between life expectancy and quality of life is increasing due to the raising prevalence of chronic diseases. Musculoskeletal disorders and chronic wounds affect a growing percentage of people and demand more efficient tools for regenerative medicine. Scaffolds that can better mimic the natural physical stimuli that tissues receive under healthy conditions and during healing may significantly aid the regeneration process. Shape, mechanical properties, pore size and interconnectivity have already been demonstrated to be relevant scaffold features that can determine cell adhesion and differentiation. Much less attention has been paid to scaffolds that can deliver more dynamic physical stimuli, such as electrical signals. Recent developments in the precise measurement of electrical fields in vivo have revealed their key role in cell movement (galvanotaxis), growth, activation of secondary cascades, and differentiation to different lineages in a variety of tissues, not just neural. Piezoelectric scaffolds can mimic the natural bioelectric potentials and gradients in an autonomous way by generating the electric stimuli themselves when subjected to mechanical loads or, if the patient or the tissue lacks mobility, ultrasound irradiation. This review provides an analysis on endogenous bioelectrical signals, recent developments on piezoelectric scaffolds for bone, cartilage, tendon and nerve regeneration, and their main outcomes in vivo. Wound healing with piezoelectric dressings is addressed in the last section with relevant examples of performance in animal models. Results evidence that a fine adjustment of material composition and processing (electrospinning, corona poling, 3D printing, annealing) provides scaffolds that act as true emitters of electrical stimuli that activate endogenous signaling pathways for more efficient and long-term tissue repair.

pH-responsive scaffolds for tissue regeneration: In vivo performance.

A myriad of pH-sensitive scaffolds has been reported in recent decades. Information on their behaviour in vitro under conditions that mimic the pH changes that occur during tissue regeneration is abundant. Differently, the in vivo demonstration of the advantages of pH-responsive systems in comparison with non-responders is more limited. The in vivo scenario is very complex and the intricate relationship between the host response, the overall pathological conditions of the patient, and the risk of colonization by microorganisms is very difficult to imitate in in vitro tests. This review aims to shed light on how the changes in pH between healthy and damaged states and also during the healing process have been exploited so far to develop polymer-based scaffolds that actively contribute in vivo to the healing process avoiding chronification. The main strategies so far tested to prepare pH-responsive scaffolds rely on (i) changes in ionization of natural polymers, ionizable monomers and clays, (ii) reversible cross-linkers, (iii) coatings, and (iv) production of CO2 gas. These strategies are analysed in detail in this review with the description of relevant examples of their performance on specific animal models. The versatility of the techniques used to prepare biocompatible and environment-friendly pH-responsive scaffolds that have been implemented in the last decade may pave the way for a successful translation to the clinic. STATEMENT OF SIGNIFICANCE: We report here on the most recent advances in pH-responsive polymer-based scaffolds that have been demonstrated in vivo to be suitable for wound and bone healing. pH is a critical variable in the tissue regeneration process, and small changes can speed up or completely stop the process. Although there is still a paucity of information on the performance in the complex in vivo environment, recently reported achievements using scaffolds endowed with pH-responsiveness through ionic natural polymers, ionizable monomers and clays, reversible cross-linkers, coatings, or formation of CO2 ensure a promising future towards clinical translation.