The history of biomaterials dates back to the mists of time: human beings had always used exogenous materials to facilitate wound healing and try to restore damaged tissues and organs. Nowadays, a wide variety of materials are commercially available and many others are under investigation to both maintain and restore bodily functions. Emerging clinical needs forced the development of new biomaterials, and lately discovered biomaterials allowed for the performing of new clinical applications. The definition of biomaterials as materials specifically conceived for biomedical uses was raised when it was acknowledged that they have to possess a fundamental feature: biocompatibility. At first, biocompatibility was mainly associated with biologically inert substances; around the 1970s, bioactivity was first discovered and the definition of biomaterials was consequently extended. At present, it also includes biologically derived materials and biological tissues. The present work aims at walking across the history of biomaterials, looking towards the scientific literature published on this matter. Finally, some current applications of biomaterials are briefly depicted and their future exploitation is hypothesized.

Hybrid biomaterials allow for the improvement of the biological properties of materials and have been successfully used for implantology in medical applications. The covalent and selective functionalization of materials with bioactive peptides provides favorable results in tissue engineering by supporting cell attachment to the biomaterial through biochemical cues and interaction with membrane receptors. Since the functionalization with bioactive peptides may alter the chemical and physical properties of the biomaterials, in this study we characterized the biological responses of differently functionalized chitosan analogs. Chitosan analogs were produced through the reaction of GRGDSPK (RGD) or FRHRNRKGY (HVP) sequences, both carrying an aldehyde-terminal group, to chitosan. The bio-functionalized polysaccharides, pure or “diluted” with chitosan, were chemically characterized in depth and evaluated for their antimicrobial activities and biocompatibility toward human primary osteoblast cells. The results obtained indicate that the bio-functionalization of chitosan increases human-osteoblast adhesion (p < 0.005) and proliferation (p < 0.005) as compared with chitosan. Overall, the 1:1 mixture of HVP functionalized-chitosan:chitosan is the best compromise between preserving the antibacterial properties of the material and supporting osteoblast differentiation and calcium deposition (p < 0.005 vs. RGD). In conclusion, our results reported that a selected concentration of HVP supported the biomimetic potential of functionalized chitosan better than RGD and preserved the antibacterial properties of chitosan.

Bladder cancer (BC) is among the most common malignancies in the world and a relevant cause of cancer mortality. BC is one of the most frequent causes for bladder removal through radical cystectomy, the gold-standard treatment for localized muscle-invasive and some cases of high-risk, non-muscle-invasive bladder cancer. In order to restore urinary functionality, an autologous intestinal segment has to be used to create a urinary diversion. However, several complications are associated with bowel-tract removal, affecting patients’ quality of life. The present study project aims to develop a bio-engineered material to simplify this surgical procedure, avoiding related surgical complications and improving patients’ quality of life. The main novelty of such a therapeutic approach is the decellularization of a porcine small intestinal submucosa (SIS) conduit to replace the autologous intestinal segment currently used as urinary diversion after radical cystectomy, while avoiding an immune rejection. Here, we performed a preliminary evaluation of this acellular product by developing a novel decellularization process based on an environmentally friendly, mild detergent, i.e., Tergitol, to replace the recently declared toxic Triton X-100. Treatment efficacy was evaluated through histology, DNA, hydroxyproline and elastin quantification, mechanical and insufflation tests, two-photon microscopy, FTIR analysis, and cytocompatibility tests. The optimized decellularization protocol is effective in removing cells, including DNA content, from the porcine SIS, while preserving the integrity of the extracellular matrix despite an increase in stiffness. An effective sterilization protocol was found, and cytocompatibility of treated SIS was demonstrated from day 1 to day 7, during which human fibroblasts were able to increase in number and strongly organize along tissue fibres. Taken together, this in vitro study suggests that SIS is a suitable candidate for use in urinary diversions in place of autologous intestinal segments, considering the optimal results of decellularization and cell proliferation. Further efforts should be undertaken in order to improve SIS conduit patency and impermeability to realize a future viable substitute.

Esophageal reconstruction through bio-engineered allografts that highly resemble the peculiar properties of the tissue extracellular matrix (ECM) is a prospective strategy to overcome the limitations of current surgical approaches. In this work, human esophagus was decellularized for the first time in the literature by comparing three detergent-enzymatic protocols. After decellularization, residual DNA quantification and histological analyses showed that all protocols efficiently removed cells, DNA (<50 ng/mg of tissue) and muscle fibers, preserving collagen/elastin components. The glycosaminoglycan fraction was maintained (70–98%) in the decellularized versus native tissues, while immunohistochemistry showed unchanged expression of specific ECM markers (collagen IV, laminin). The proteomic signature of acellular esophagi corroborated the retention of structural collagens, basement membrane and matrix–cell interaction proteins. Conversely, decellularization led to the loss of HLA-DR expression, producing non-immunogenic allografts. According to hydroxyproline quantification, matrix collagen was preserved (2–6 µg/mg of tissue) after decellularization, while Second-Harmonic Generation imaging highlighted a decrease in collagen intensity. Based on uniaxial tensile tests, decellularization affected tissue stiffness, but sample integrity/manipulability was still maintained. Finally, the cytotoxicity test revealed that no harmful remnants/contaminants were present on acellular esophageal matrices, suggesting allograft biosafety. Despite the different outcomes showed by the three decellularization methods (regarding, for example, tissue manipulability, DNA removal, and glycosaminoglycans/hydroxyproline contents) the ultimate validation should be provided by future repopulation tests and in vivo orthotopic implant of esophageal scaffolds.

The main purpose of tissue engineering is to fabricate and exploit engineered constructs suitable for the effective replacement of damaged tissues and organs to perfectly integrate with the host’s organism without eliciting any adverse reaction. Ideally, autologous materials represent the best option, but they are often limited due to the low availability of compatible healthy tissues. So far, one therapeutic approach relies on the exploitation of synthetic materials as they exhibit good features in terms of impermeability, deformability, and flexibility, but present chronic risks of infections and inflammations. Alternatively, biological materials, including naturally derived ones and acellular tissue matrices of human or animal origin, can be used to induce cells growth and differentiation, which are needed for tissue regeneration; however, this kind of material lacks satisfactory mechanical resistance and reproducibility, affecting their clinical application. In order to overcome the above-mentioned limitations, hybrid materials, which can be obtained by coupling synthetic polymers and biological materials, have been investigated with the aim to improve biological compatibility and mechanical features. Currently, the interest in these materials is growing, but the ideal ones have not been found yet. The present review aims at exploring some applications of hybrid materials, with particular mention to urological and cardiovascular fields. In the first case, the efforts to find a construct that can guarantee impermeability, mechanical resistance, and patency is herein illustrated; in the second case, the search for impermeability, hemocompatibility and adequate compliance is disclosed.

With the increasing number of people suffering from heart valve diseases (e.g., stenosis and/or insufficiency), the attention paid to prosthetic heart valves has grown significantly. Developing a prosthetic device that fully replaces the functionality of the native valve remains a huge challenge. Polymeric heart valves (PHVs) represent an appealing option, offering the potential to combine the robustness of mechanical valves with the enhanced biocompatibility of bioprosthetic ones. Over the years, novel biomaterials (such as promising new polymers and nanocomposites) and innovative designs have been explored for possible applications in manufacturing PHVs. This work provides a comprehensive overview of PHVs’ evolution in terms of materials, design, and fabrication techniques, including in vitro and in vivo studies. Moreover, it addresses the drawbacks associated with PHV implementation, such as their limited biocompatibility and propensity for sudden failure in vivo. Future directions for further development are presented. Notably, PHVs can be particularly relevant for transcatheter application, the most recent minimally invasive approach for heart valve replacement. Despite current challenges, PHVs represent a promising area of research with the potential to revolutionize the treatment of heart valve diseases, offering more durable and less invasive solutions for patients.