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Soft tissue defects, such as incisional hernia or pelvic organ prolapse, are prevalent pathologies characterized by a tissue microenvironment rich in fragile and dysfunctional fibroblasts. Precision medicine could improve their surgical repair, currently based on polymeric materials. Nonetheless, biomaterial-triggered interventions need first a better understanding of the cell-material interfaces that truly consider the patients’ biology. Few tools are available to study the interactions between polymers and dysfunctional soft tissue cells in vitro. Here, we propose polypropylene (PP) as a matrix to create microscale surfaces w/wo functionalization with an HBII-RGD molecule, a fibronectin fragment modified to include an RGD sequence for promoting cell attachment and differentiation. Metal mold surfaces were roughened by shot blasting with aluminum oxide, and polypropylene plates were obtained by injection molding. HBII-RGD was covalently attached by silanization. As a proof of concept, primary abdominal and vaginal wall fasciae fibroblasts from control patients were grown on the new surfaces. Tissue-specific significant differences in cell morphology, early adhesion and cytoskeletal structure were observed. Roughness and biofunctionalization parameters exerted unique and combinatorial effects that need further investigation. We conclude that the proposed model is effective and provides a new framework to inform the design of smart materials for the treatment of clinically compromised tissues., The authors acknowledge the financial support by Instituto de Salud Carlos III (ISCIII) via grant PI17/01236 from the program Acción Estratégica en Salud 2018–2020 (Spanish Ministry of Science and Innovation). This project was also supported by the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR), file no 2021 SGR 00210, from the Department of Research and Universities (Generalitat de Catalunya, Spain). J.G.-M. acknowledges the Maria Zambrano fellowship funded by European Union-NextGeneration, EU, Ministry of Universities and Recovery, Transformation and Resilience Plan, through a call from Universitat Politècnica de Catalunya (Grant Ref. 2021UPC-MZ-67143). This research was funded by the Ministry of Science and Innovation of Spain through the PID2021-125150OB-I00 project., Peer Reviewed, Postprint (published version)

The Boston keratoprosthesis (BKPro) is a medical device used to restore vision in complicated cases of corneal blindness. This device is composed by a front plate of polymethylmethacrylate (PMMA) and a backplate usually made of titanium (Ti). Ti is an excellent biomaterial with numerous applications, although there are not many studies that address its interaction with ocular cells. In this regard, despite the good retention rates of the BKPro, two main complications compromise patients' vision and the viability of the prosthesis: imperfect adhesion of the corneal tissue to the upside of the backplate and infections. Thus, in this work, two topographies (smooth and rough) were generated on Ti samples and tested with or without functionalization with a dual peptide platform. This molecule consists of a branched structure that links two peptide moieties to address the main complications associated with BKPro: the well-known RGD peptide in its cyclic version (cRGD) as cell pro-adherent motif and the first 11 residues of lactoferrin (LF1–11) as antibacterial motif. Samples were physicochemically characterized, and their biological response was evaluated in vitro with human corneal keratocytes (HCKs) and against the gram-negative bacterial strain Pseudomonas aeruginosa. The physicochemical characterization allowed to verify the functionalization in a qualitative and quantitative manner. A higher amount of peptide was anchored to the rough surfaces. The studies performed using HCKs showed increased long-term proliferation on the functionalized samples. Gene expression was affected by topography and peptide functionalization. Roughness promoted a-smooth muscle actin (a-SMA) overexpression, and the coating notably increased the expression of extracellular matrix components (ECM). Such changes may favour the development of unwanted fibrosis, and thus, corneal haze. In contrast, the combination of the coating with a rough topography decreased the expression of a-SMA and ECM c, Peer Reviewed, Postprint (published version)

The formation of a biological seal around the neck of titanium (Ti) implants is critical for ensuring integration at the gingival site and for preventing bacterialcolonization that may lead to periimplantitis. This process is guided byactivated fibroblasts, named myofibroblasts, which secrete extracellularmatrix (ECM) proteins and ECM-degrading enzymes resolving the wound.However, in some cases, Ti is not able to attract and activate fibroblasts to asufficient extent, which may compromise the success of the implant.Fibronectin (FN) is an ECM component found in wounds that is able to guidesoft tissue healing through the adhesion of cells and attraction of growthfactors (GFs). However, clinical use of FN functionalized Ti implants isproblematic because FN is difficult to obtain, and is sensitive to degradation.Herein, functionalizing Ti with a modified recombinant heparin binding II(HBII) domain of FN, mutated to include an Arg-Gly-Asp (RGD) sequence forpromoting both fibroblast adhesion and GF attraction, is aimed at. TheHBII-RGD domain is able to stimulate fibroblast adhesion, spreading,proliferation, migration, and activation to a greater extent than the nativeHBII, reaching values closer to those of full-length FN suggesting that itmight induce the formation of a biological sealing., Peer Reviewed, Postprint (published version)

The 3D printing of titanium (Ti) offers countless possibilities for the development of personalized implants with suitable mechanical properties for different medical applications. However, the poor bioactivity of Ti is still a challenge that needs to be addressed to promote scaffold osseointegration. The aim of the present study was to functionalize Ti scaffolds with genetically modified elastin-like recombinamers (ELRs), synthetic polymeric proteins containing the elastin epitopes responsible for their mechanical properties and for promoting mesenchymal stem cell (MSC) recruitment, proliferation, and differentiation to ultimately increase scaffold osseointegration. To this end, ELRs containing specific cell-adhesive (RGD) and/or osteoinductive (SNA15) moieties were covalently attached to Ti scaffolds. Cell adhesion, proliferation, and colonization were enhanced on those scaffolds functionalized with RGD-ELR, while differentiation was promoted on those with SNA15-ELR. The combination of both RGD and SNA15 into the same ELR stimulated cell adhesion, proliferation, and differentiation, although at lower levels than those for every single moiety. These results suggest that biofunctionalization with SNA15-ELRs could modulate the cellular response to improve the osseointegration of Ti implants. Further investigation on the amount and distribution of RGD and SNA15 moieties in ELRs could improve cell adhesion, proliferation, and differentiation compared to the present study., Peer Reviewed, Postprint (published version)

Presentació del Guillem Martí (grup BBT-UPC) sobre els elements a tenir en compte alhora de desenvolupar un Pla de Gestió de Dades - Data Management Plan., Objectius de Desenvolupament Sostenible::4 - Educació de Qualitat, Objectius de Desenvolupament Sostenible::10 - Reducció de les Desigualtats

A lack of primary stability and osteointegration in metallic implants may result in implant loosening and failure. Adding porosity to metallic implants reduces the stress shielding effect and improves implant performance, allowing the surrounding bone tissue to grow into the scaffold. However, a bioactive surface is needed to stimulate implant osteointegration and improve mechanical stability. In this study, porous titanium implants were produced via powder sintering to create different porous diameters and open interconnectivity. Two strategies were used to generate a bioactive surface on the metallic foams: (1) an inorganic alkali thermochemical treatment, (2) grafting a cell adhesive tripeptide (RGD). RGD peptides exhibit an affinity for integrins expressed by osteoblasts, and have been reported to improve osteoblast adhesion, whereas the thermochemical treatment is known to improve titanium implant osseointegration upon implantation. Bioactivated scaffolds and control samples were implanted into the tibiae of rabbits to analyze the effect of these two strategies in vivo regarding bone tissue regeneration through interconnected porosity. Histomorphometric evaluation was performed at 4 and 12 weeks after implantation. Bone-to-implant contact (BIC) and bone in-growth and on-growth were evaluated in different regions of interest (ROIs) inside and outside the implant. The results of this study show that after a long-term postoperative period, the RGD-coated samples presented higher quantification values of quantified newly formed bone tissue in the implant’s outer area. However, the total analyzed bone in-growth was observed to be slightly greater in the scaffolds treated with alkali thermochemical treatment. These results suggest that both strategies contribute to enhancing porous metallic implant stability and osteointegration, and a combination of both strategies might be worth pursuing., Peer Reviewed, Postprint (author's final draft)

BACKGROUND Orthopedic implant-related infection remains one of the most serious complications after orthopedic surgery. In recent years, there has been an increased scientific interest to improve prevention and treatment strategies. However, many of these strategies have focused on chemical measures. AIM To analyze the effect of alternating current electrical fields on bacterial adherence to titanium surfaces. METHODS Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were exposed to 6.5 V electrical currents at different frequencies: 0.5 Hz, 0.1 Hz, and 0.05 Hz. After exposure, a bacterial count was then performed and compared to the control model. Other variables registered included the presence of electrocoagulation of the medium, electrode oxidation and/or corrosion, and changes in pH of the medium. RESULTS The most effective electrical model for reducing S. aureus adhesion was 6.5 V alternating current at 0.05 Hz achieving a 90% adhesion reduction rate. For E. coli, the 0.05 Hz frequency model also showed the most effective results with a 53% adhesion reduction rate, although these were significantly lower than S. aureus. Notable adhesion reduction rates were observed for S. aureus and E.coli in the studied conditions. However, the presence of electrode oxidation makes us presume these conditions are not optimal for in vivo use. CONCLUSION Although our findings suggest electrical currents may be useful in preventing bacterial adhesion to metal surfaces, further research using other electrical conditions must be examined to consider their use for in vivo trials., Peer Reviewed, Postprint (published version)