Amorphous calcium phosphate (ACP) is proposed as a precursor phase in biologically controlled mineralization processes in both vertebrates and invertebrates. Therefore, there are increasing studies to understand the ACP stability in biomineralization events, as well as to use them in the development of hybrid scaffolds biomimetic of mineralized biological tissues. Its structural instability and uncontrolled crystallization under physiological conditions in vitro have limited its use for such different purposes, often requiring high concentrations of non-physiological stabilizing agents. Here, we present a one-pot, spray-drying-based, and scalable method for the rapid fabrication of either ACP or hybrid ACP-collagen microparticles. The microparticles containing acetate, lacking counterions of ACP precursor salts such as Na+ and Cl-, exhibit remarkable long-term and thermal stability, and do not require the high concentrations of inorganic ions typically used for stabilization. In addition, from an applied perspective, they can form under physiological conditions biomimetic bone mineral but also, in the presence of collagen, extrudable 3D fibrillar bone-like constructs. Finally, our work complements the understanding of ACP stabilization and its integration within organic scaffolds, both of which are essential for understanding biomineralization processes.

Polyetheretherketone (PEEK) has emerged as a promising biomaterial for orthopedic and craniofacial implants due to its favorable mechanical properties and fatigue resistance; however, its inherent chemical inertness limits effective osseointegration. In this study, femtosecond laser surface modification is explored as a strategy to enhance the bioactivity of PEEK. Based on a previously performed parametric study, controlled micro- and nanoscale surface textures were fabricated using femtosecond laser processing, enabling precise tuning of surface roughness and wettability without the need for additional chemical treatment. The modified surfaces were systematically characterized in terms of morphology, composition, and topography using scanning electron microscopy (SEM), 3D profilometry, and water contact angle measurements. Four optimized femtosecond laser-generated surface architectures were selected for the present investigation and comprehensively characterized, followed by in vitro evaluation of dental pulp stem cell adhesion, morphology, and proliferation. The results indicate that laser-induced micro/nanostructuring enhances the surface properties of PEEK, while supporting cellular attachment and favorable cell–surface interaction. Differences in the biological response were observed among the optimized laser-textured surfaces. These findings highlight the feasibility of femtosecond laser texturing as a clean, reproducible, and scalable approach for the development of next-generation, personalized orthopedic implants.

Extracellular matrix (ECM)-based hydrogels are increasingly used in regenerative medicine; however, animalderived sources such as rat tail tendon ECM (RT-ECM)-the current gold standard-face limitations for clinical translation. We propose hydrogels derived from decellularized human Wharton's jelly (WJ-ECM) as a bioactive and sustainable alternative. Compared to RT-ECM, WJ-ECM hydrogels exhibit a distinct biochemical composition, combining type I/III collagen and glycosaminoglycans, and form thinner fibrils. Upon exposure to culture medium, they display reduced syneresis. Rheological and confined compression tests reveal lower stiffness and decreased permeability. Functionally, WJ-ECM hydrogels demonstrate superior hemostatic properties, reduce intracellular ROS accumulation in neutrophils, and promote an anti-inflammatory phenotype in macrophages. In vivo implantation confirms their biocompatibility with minimal adverse effects. These results highlight the potential of WJ-ECM hydrogels as a clinically relevant biomaterial for regenerative medicine and cell culture applications.

Mechanobiology integrates biological and mechanical cues to provide a comprehensive understanding of how physical forces influence tissue regeneration, specifically focusing on bone growth and repair. This review presents a comprehensive overview of the latest developments in bone mechanobiology and highlights the remaining scientific and methodological challenges. Following a brief presentation of the challenges facing cell therapy, and in particular the application of different types of mechanical stimuli, the article examines these various processes on cells and tissues such as compressors and bioreactors operating at low frequencies (in the Hz range). Special attention is given to cutting-edge ultrasound techniques, such as the LIPUS method with MHz frequencies and low intensities ranging from 0.5 to 100 mW/cm², and with an emphasis on the emerging application of acoustic levitation with frequencies ranging from 340 kHz to 2.12 MHz permitting non-invasive manipulation of cells and tissues in biological research, with initial beneficial results in cell therapy. Lastly, the review offers a detailed analysis of multi-scale and multi-physics in silico approaches that may contribute to interpret the obtained experimental results. Agent-based models capture the discrete behaviour of individual cells, while continuum models describe tissue mechanics though averaged properties, offering complementary approaches to study complex mechanobiological phenomena. Such approaches hold the potential to drive transformative advances in bone regeneration medicine, providing a roadmap for future research.

The Wharton's jelly, a mucoid connective tissue of the umbilical cord, is promising for regenerative medicine applications. However it is relatively new and poorly documented especially from a mechanical point of view. To help filling the gap in the literature lack of data, this study seeks to address the Wharton's jelly damage behavior by providing first key results through an efficient analytical approach. The tensile and damage behavior of Wharton's jelly membranes is studied using tensile tests conducted up to failure under close physiological conditions. The Wharton's jelly mechanical response has been characterized using an hyperelastic constitutive model based on the Ogden formulation, enhanced with continuum damage mechanics to capture analytically the damage behavior. To support the mechanical analysis, optical coherence tomography was used to assess the stress-free microstructural arrangement of the collagen fibers, revealing a transversely isotropic architecture. This qualitative insight into the internal structure enriched the interpretation of the mechanical behavior. Overall, this analytical study enabled the identification of a comprehensive set of material parameters characterizing both elastic and damage responses. Pearson correlation matrices were used to reveal meaningful relationships between parameters, potential predictive descriptors, and model's limitations. These findings provide a solid foundation for future modeling developments through numerical simulation and offer new outlooks for surgery and dressing applications.

Human amniotic membrane (hAM) has been extensively used for several decades as a bioactive scaffold for regenerative medicine. In its cryopreserved form—one of the main storage formats—the presence of viable cells has often been questioned. Furthermore, there is little published evidence of the role of endogenous amniotic cells from cryopreserved hAM in tissue repair.Some technologies, often patented and combined, have facilitated the use of hAM. Decellularization and devitalization processes have been developed to ensure its safety and prevent immune rejection. Lyophilization and dehydration methods have had a significant impact on clinical practices by enabling storage at room temperature in the operating room and making handling and cutting easier. Consequently, the commercialization of hAM has expanded, initially in the USA, and now in Europe.In the last decade, there has been growing interest in new perinatal tissues in clinical medicine. Similar processes have been adapted for these tissues to prevent immune or inflammatory reactions, and to improve storage and make them easier to use. For example, in the USA, many products marketed for wound healing undergo lyophilization, sometimes in combination with decellularization.Given our expertise, we wanted to highlight the potential of decellularized/devitalized and lyophilized perinatal tissues in regenerative medicine, particularly for bone repair. In this opinion paper, we discuss why these tissues represent the future of regenerative medicine, their potential drawbacks and strategies to overcome these challenges.

Injectable hydrogels are promising candidates as local drug delivery platforms for the treatment of infected wounds. Self‐assembled small peptide hydrogels are of interest due to their high biocompatibility, degradability, and ease of synthesis. This study describes the formation of an injectable hydrogel based on the self‐assembly of Fmoc‐FFpY (Fmoc: fluorenylmethoxycarbonyl, F: phenylalanine, pY: tyrosine phosphate) triggered by electrostatic interactions in the presence of Fe3+ ions. Stabilized by H bonding and π–π stacking, the hydrogels exhibit high mechanical stiffness with a G′ (storage modulus) of ≈8000 Pa and a self‐recovery up to G′ ≈100 Pa. Peptide self‐assembly yields β‐sheets twisted into fibrillar helices of 12 nm in diameter and pitch. Molecular dynamics simulations confirm 1) the aggregation of Fmoc‐FFpY in the presence of Fe3+ and the adopted secondary structure and show that 2) the aggregated Fmoc‐FFpY/Fe3+ disrupts the bacterial membrane of Staphylococcus aureus and Pseudomonas aeruginosa, favoring the passive entry of Fe3+ into the pathogen. In full agreement with the simulations, the hydrogels exhibit antibacterial activity against both bacteria, likely due to the increased Fe3+ entry into the cell, resulting in enhanced production of reactive oxygen species. This work paves the way for ferroptosis‐inducing treatment of bacterial infections using injectable ultrashort peptides.

Decellularized extracellular matrix is a promising material for regenerative medicine applications. Decellularized Wharton's jelly (WJ) is considered as a favorable allograft based material due to its biological properties including antibacterial activities, and immunomodulation. However, the rapid degradation and poor mechanical behavior of WJ derived membranes in biological environment hinders their application in guided bone regeneration. In this study, we have demonstrated that tannic acid (TA), a natural polyphenol, is an efficient cross-linking agent to significantly improve the mechanical properties and the enzymatic stability of WJ membranes. In addition, the post-oxidation of WJ-TA membranes, by sodium periodate, endowed superior biological properties. Indeed, WJ-TA oxidized (WJ-TA-ox) membranes showed antibacterial and antioxidant activities along with a better performance in vitro, improving primary osteoblast and dental pulp stromal cell adhesion and proliferation, and in vivo, increasing the de novo bone formation in a parietal bone defect. These results showed the osteo-biocompatibility and the great potentials of WJ-TA-ox membranes for bone regenerative medicine.

Perinatal derivatives have been proposed as adjunct therapeutic strategies or innovative treatments. Undoubtedly, perinatal derivatives can offer the opportunity and source material to isolate multipotent stem cells, but both maternal- and fetal-derived tissues can be processed and transformed into engineered tissues or advanced biomedical devices, whose potential remains to be fully elucidated. Promising preclinical and clinical results collected so far clearly foresee an escalation of such novel treatments. Market forecasts predict exponential growth in such advanced medicinal products during the next decade, with a pragmatic innovation for medicine into a more advanced biomedical version, enlarging the portfolio for treating a wide range of congenital and acute conditions. However, all these promising and fascinating therapeutic possibilities cannot gain a solid and recognized role in established medical practice without rigid and harmonized manufacturing strategies. The implementation of strategies according to guidelines and directives compiled by Regulatory Agencies, in conformity to (European) Pharmacopoeia and for Good Manufacturing Practice -conforming production of such products, represent critical steps required to translate perinatal technologies into effective therapeutic approaches. During the past 5 years, a panel of European experts and developers, gathered under the umbrella of the COST Sprint Action, supported by the European Cooperation in Science and Technology action, had the opportunity to revise and summarize experience and recommendations for a fruitful and proficient generation of perinatal biomedical products. In order to facilitate the creation and potential commercialization of perinatal bioengineered and advanced pharmaceutical products and technologies, such a collection of data and recommendations is described and discussed here.

The surface engineering of biomaterials is crucial for their successful (bio)integration by the body, i.e. the colonization by the tissue-specific cell, and the prevention of fibrosis and/or bacterial colonization. Performed at room temperature in an aqueous medium, the layer-by-layer (LbL) coating method is based on the alternating deposition of macromolecules. Versatile and simple, this method allows the functionalization of surfaces with proteins, which play a crucial role in several biological mechanisms. Possessing intrinsic properties (cell adhesion, antibacterial, degradable, etc.), protein-based LbL films represent a powerful tool to control bacterial and mammalian cell fate. In this article, after a general introduction to the LbL technique, we will focus on protein-based LbL films addressing different biomedical issues/domains, such as bacterial infection, blood contacting surfaces, mammalian cell adhesion, drug and gene delivery, and bone and neural tissue engineering. We do not consider biosensing applications or electrochemical aspects using specific proteins such as enzymes.

Wharton's Jelly (WJ) has attracted significant interest in the field of tissue healing thanks to its biological properties, including antibacterial activity and immunomodulation. However, due to the fast degradation and poor mechanical behavior in biological environment, its application in bone regeneration is compromised. Here, we proposed to use genipin as an efficient cross-linking agent to significantly improve the elasticity and the enzymatical stability of the WJ matrix. The degree of cross-linking, linear elastic moduli, and collagenase resistance varied over a wide range depending on genipin concentration. Furthermore, our results highlighted that an increase in genipin concentration led to a decreased surface wettability, therefore impairing cell attachment and proliferation. The genipin cross-linking prevented rapid in vitro and in vivo degradation, but led to an adverse host reaction and calcification. When implanted in the parietal bone defect, a limited parietal bone regeneration to the dura was observed. We conclude that genipin-cross-linked WJ is a versatile medical device however, a careful selection is required with regards to the genipin concentration.

Objectives The aim of this study was to investigate the potential of tuning the topography of textile surfaces for biomedical applications towards modified cell-substrate interactions.Methods For that purpose, a supercritical Nitrogen N2 jet was used to spray glass particles on multi-filament polyethylene terephthalate (PET) yarns and on woven fabrics. The influence of the jet projection parameters such as the jet pressure (P) and the standoff distance (SoD) on the roughness was investigated.Results The impact of the particles created local filament ruptures on the treated surfaces towards hairiness increase. The results show that the treatment increases the roughness by up to 17 % at P 300 bars and SoD 300 mm while the strength of the material is slightly decreased. The biological study brings out that proliferation can be slightly limited on a more hairy surface, and is increased when the surface is more flat. After 10 days of fibroblast culture, the cells covered the entire surface of the fabrics and had mainly grown unidirectionally, forming cell clusters oriented along the longitudinal axis of the textile yarns. Clusters were generated at yarn crossings.Conclusions This approach revealed that the particle projection technology can help tuning the cell proliferation on a textile surface.

This study investigates the biomechanics of type 2 diabetic bone fragility through a multiscale experimental strategy that considers structural, mechanical, and compositional components of ex vivo human trabecular and cortical bone. Human tissue samples were obtained from the femoral heads of patients undergoing total hip replacement. Mechanical testing was carried out on isolated trabecular cores using monotonic and cyclic compression loading and nanoindentation experiments, with bone microdamage analysed using micro-computed tomography (CT) imaging. Bone composition was evaluated using Raman spectroscopy, high-performance liquid chromatography, and fluorometric spectroscopy. It was found that human type 2 diabetic bone had altered mechanical, compositional, and morphological properties compared to non-type 2 diabetic bone. High-resolution micro-CT imaging showed that cores taken from the central trabecular region of the femoral head had higher bone mineral density (BMD), bone volume, trabecular thickness, and reduced trabecular separation. Type 2 diabetic bone also had enhanced macro-mechanical compressive properties under mechanical loading compared to non-diabetic controls, with significantly higher apparent modulus, yield stress, and pre-yield toughness evident, even when properties were normalised against the bone volume. Using nanoindentation, there were no significant differences in the tissue-level mechanical properties of cortical or trabecular bone in type 2 diabetic samples compared to controls. Through compositional analysis, higher levels of furosine were found in type 2 diabetic trabecular bone, and an increase in both furosine and carboxymethyl-lysine (an advanced glycation end-product) was found in cortical bone. Raman spectroscopy showed that type 2 diabetic bone had a higher mineral-to-matrix ratio, carbonate substitution, and reduced crystallinity compared to the controls. Together, this study shows that type 2 diabetes leads to distinct changes in both organic and mineral phases of the bone tissue matrix, but these changes did not coincide with any reduction in the micro- or macro-mechanical properties of the tissue under monotonic or cyclic loading.