Review article laser-induced hyperthermia on graphene oxide composites

Background: Hyperthermia-based therapies have shown great potential for clinical applications such as for the antitumor and antipathogenic activities. Within all strategies, the so-called photothermal therapy proposes to induce the hyperthermia by the remote laser radiation on a photothermal conversion agent, in contact with the target tissue. Methods: This paper reviews the most relevant in vitro and in vivo studies focused on NIR laser-induced hyperthermia due to photoexcitation of graphene oxide (GO) and reduced graphene oxide (rGO). Relevant parameters such as the amount of GO/rGO, the influence of the laser wavelength and power density are considered. Moreover, the required temperature and exposure time for each antitumor/antipathogenic case are collected and unified in a thermal dose parameter: the CEM43. Results: The calculated CEM43 thermal doses revealed a great variability for the same type of tumor/strain. In order to detect potential tendencies, the values were classified into four ranges, varying from CEM4360ºC). Conclusions: The ability of GO/rGO as effective photothermal conversion agents to promote a controlled hyperthermia is proven. The variability found for the CEM43 thermal doses on the reviewed studies reveals the potentiality to evaluate, for each application, the use of lower temperatures, by modulating time and/or repetitions in the dosesMinisterio de Ciencia e Innovación del Gobierno de España | Ref. BIOHEAT (PID 2020- 115415RB-100)Xunta de Galicia | Ref. GRC (ED431C 2021/49

Physicochemical properties of 3D-printed polylactic acid/hydroxyapatite scaffolds

The reconstruction or regeneration of damaged bone tissue is one of the challenges of orthopedic surgery and tissue engineering. Among all strategies investigated, additive manufacturing by fused deposition modeling (3D-FDM printing) opens the possibility to obtain patient-specific scaffolds with controlled architectures. The present work evaluates in depth 3D direct printing, avoiding the need for a pre-fabricated filament, to obtain bone-related scaffolds from direct mixtures of polylactic acid (PLA) and hydroxyapatite (HA). For it, a systematic physicochemical characterization (SEM-EDS, FT-Raman, XRD, micro-CT and nanoindentation) was performed, using different PLA/HA ratios and percentages of infill. Results prove the versatility of this methodology with an efficient HA incorporation in the 3D-printed scaffolds up to 13 wt.% of the total mass and a uniform distribution of the HA particles in the scaffold at the macro level, both longitudinal and cross sections. Moreover, an exponential distribution of the HA particles from the surface toward the interior of the biocomposite cord (micro level), within the first 80 µm (10% of the entire cord diameter), is also confirmed, providing the scaffold with surface roughness and higher bioavailability. In relation to the pores, they can range in size from 250 to 850 µm and can represent a percentage, in relation to the total volume of the scaffold, from 24% up to 76%. The mechanical properties indicate an increase in Young’s modulus with the HA content of up to ~50%, compared to the scaffolds without HA. Finally, the in vitro evaluation confirms MG63 cell proliferation on the 3D-printed PLA/HA scaffolds after up to 21 days of incubation

3D-printed PLA medical devices: physicochemical changes and biological response after sterilisation treatments

Financiado para publicación en acceso aberto: Universidade de Vigo/CISUGPolylactic acid (PLA) has become one of the most commonly used polymers in medical devices given its biocompatible, biodegradable and bioabsorbable properties. In addition, due to PLA’s thermoplastic behaviour, these medical devices are now obtained using 3D printing technologies. Once obtained, the 3D-printed PLA devices undergo different sterilisation procedures, which are essential to prevent infections. This work was an in-depth study of the physicochemical changes caused by novel and conventional sterilisation techniques on 3D-printed PLA and their impact on the biological response in terms of toxicity. The 3D-printed PLA physicochemical (XPS, FTIR, DSC, XRD) and mechanical properties as well as the hydrophilic degree were evaluated after sterilisation using saturated steam (SS), low temperature steam with formaldehyde (LTSF), gamma irradiation (GR), hydrogen peroxide gas plasma (HPGP) and CO2 under critical conditions (SCCO). The biological response was tested in vitro (fibroblasts NCTC-929) and in vivo (embryos and larvae wild-type zebrafish Danio rerio). The results indicated that after GR sterilisation, PLA preserved the O:C ratio and the semi-crystalline structure. Significant changes in the polymer surface were found after HPGP, LTSF and SS sterilisations, with a decrease in the O:C ratio. Moreover, the FTIR, DSC and XRD analysis revealed PLA crystallisation after SS sterilisation, with a 52.9% increase in the crystallinity index. This structural change was also reflected in the mechanical properties and wettability. An increase in crystallinity was also observed after SCCO and LTSF sterilisations, although to a lesser extent. Despite these changes, the biological evaluation revealed that none of the techniques were shown to promote the release of toxic compounds or PLA modifications with toxicity effects. GR sterilisation was concluded as the least reactive technique with good perspectives in the biological response, not only at the level of toxicity but at all levels, since the 3D-printed PLA remained almost unaltered.POCTEP INTERREG España- Portugal | Ref. BLUEBIOLABInterreg Atlantic Area | Ref. BLUEHUMAN EAPA_151/2016Ministerio de Ciencia e Innovación | Ref. PID 2020-115415RB-100Xunta de Galicia | Ref. ED431C 2021/49Xunta de Galicia | Ref. ED481A 2019/314Xunta de Galicia | Ref. IN606A-2017/011Fundação para a Ciência e a Tecnologia | Ref. UIDB/50016/202

Vancomycin-loaded 3D-printed polylactic acid–hydroxyapatite scaffolds for bone tissue engineering

The regeneration of bone remains one of the main challenges in the biomedical field, with the need to provide more personalized and multifunctional solutions. The other persistent challenge is related to the local prevention of infections after implantation surgery. To fulfill the first one and provide customized scaffolds with complex geometries, 3D printing is being investigated, with polylactic acid (PLA) as the biomaterial mostly used, given its thermoplastic properties. The 3D printing of PLA in combination with hydroxyapatite (HA) is also under research, to mimic the native mechanical and biological properties, providing more functional scaffolds. Finally, to fulfill the second one, antibacterial drugs locally incorporated into biodegradable scaffolds are also under investigation. This work aims to develop vancomycin-loaded 3D-printed PLA–HA scaffolds offering a dual functionality: local prevention of infections and personalized biodegradable scaffolds with osseointegrative properties. For this, the antibacterial drug vancomycin was incorporated into 3D-printed PLA–HA scaffolds using three loading methodologies: (1) dip coating, (2) drop coating, and (3) direct incorporation in the 3D printing with PLA and HA. A systematic characterization was performed, including release kinetics, Staphylococcus aureus antibacterial/antibiofilm activities and cytocompatibility. The results demonstrated the feasibility of the vancomycin-loaded 3D-printed PLA–HA scaffolds as drug-releasing vehicles with significant antibacterial effects for the three methodologies. In relation to the drug release kinetics, the (1) dip- and (2) drop-coating methodologies achieved burst release (first 60 min) of around 80–90% of the loaded vancomycin, followed by a slower release of the remaining drug for up to 48 h, while the (3) 3D printing presented an extended release beyond 7 days as the polymer degraded. The cytocompatibility of the vancomycin-loaded scaffolds was also confirmed.Agencia Estatal de Investigación | Ref. PID2020-115415RB-I00Xunta de Galicia | Ref. ED431C 2021/49Xunta de Galicia | Ref. ED481A 2019/31

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

3D-Printed biocomposites based on polylactic acid and hydroxyapatite

El envejecimiento de la población y las enfermedades asociadas suponen en la actualidad un importante reto social y económico, dado que cada vez son más las personas que precisan soluciones clínicas que requieren la utilización de implantes, prótesis y dispositivos biomédicos a lo largo de su vida. En este sentido, el creciente desarrollo de la ingeniería de tejidos y la medicina regenerativa conlleva la necesidad de investigar en biomateriales avanzados e inteligentes y también en procesos de fabricación innovadores. Entre estos biomateriales, los compuestos de ácido poliláctico (PLA) ofrecen una alternativa prometedora a los biomateriales tradicionales y a los polímeros no biodegradables porque es bioabsorbible, biodegradable y biocompatible. Ya es ampliamente utilizado en casi todas las especialidades médicas debido a su rápida traducibilidad clínica: aplicaciones ortopédicas (scaffolds, tornillos bioabsorbibles); aplicaciones cardíacas (stents); odontología; cirugía plástica (suturas, rellenos dérmicos, etc.); y sistemas para la liberación de fármacos. Recientemente, el interés por los dispositivos médicos basados en el PLA aumentó drásticamente, ya que es un material adecuado para las tecnologías emergentes, como la impresión 3D. Sus propiedades y su baja temperatura de transición vítrea lo hacen deformable a altas temperaturas (190-220 °C) convirtiéndolo en un de los filamentos más utilizados en esta tecnología, siendo el modelado de deposición fundida (FDM), una de las técnicas más comunes. El uso de la impresión 3D fue bien aceptado en el campo biomédico, permitiendo la rápida fabricación de estructuras personalizadas con geometrías complejas y excelente reproducibilidad para adentrarnos en la medicina personalizada. Otras estrategias para el desarrollo de biomateriales avanzados de gran interés clínico, en particular, orientados a la regeneración del tejido óseo, se basan en la utilización de compuestos de fosfato cálcico, como la hidroxiapatita y la incorporación de antibióticos para evitar infecciones postoperatorias. Los antibióticos sistémicos pueden provocar reacciones adversas no deseadas, y las concentraciones más altas están limitadas por los perfiles de excreción y la vida media de los fármacos. Así pues, un dispositivo biodegradable con antibióticos colocado en el nido de la infección o en un lugar con riesgo podría permitir la administración de un fármaco localizado y específico que puede administrarse la una concentración más alta que una dosis sistémica eliminando o manteniendo la infección controlada a medida que se va reabsorbiendo el dispositivo biodegradable. Por tanto, la combinación de PLA con estos dos materiales en forma de filamento para impresión 3D abren la posibilidad de fabricar de forma personalizada prótesis e implantes y aunando las propiedades y ventajas de todos los componentes en un único dispositivo. Por una parte, la hidroxiapatita podría mejorar las propiedades mecánicas del PLA, al concederle más rigidez y favorecerían la bioactividad y la osteointegración. Además, con la incorporación del antibiótico también se podría hacer frente a las infecciones más recurrentes del tejido óseo, como las causadas por Sthapylococcus aureus. Finalmente, debemos hablar de la importancia que tiene la esterilización, siendo un paso fundamental en el proceso de fabricación de cualquiera biomaterial o dispositivo médico que vaya a estar en contacto con el cuerpo humano con el fin de evitar cualquier complicación asociada a ellos como las infecciones o rechazos. Las técnicas convencionales de esterilización más usadas hoy en día son el vapor y la radiación gamma, pero estas pueden presentar ciertas desventajas con algunos materiales termosensibles. En este sentido, surge la noticia técnica de esterilización mediante CO2 supercrítico que, al trabajar a temperaturas próximas a la ambiental, la hace una técnica idónea para biomateriales que se degradan a altas temperaturas, como es el caso del PLA.O envellecemento da poboación e as enfermidades asociadas supoñen na actualidade un importante reto social e económico, dado que cada vez son máis as persoas que precisan solucións clínicas que requiren a utilización de implantes, próteses e dispositivos biomédicos ao longo da súa vida. Neste sentido, o crecente desenvolvemento da enxeñería de tecidos e a medicina regenerativa conleva a necesidade de investigar en biomateriales avanzados e intelixentes e tamén en procesos de fabricación innovadores. Entre estes biomateriales, os compostos de ácido poliláctico (PLA) ofrecen unha alternativa prometedora aos biomateriales tradicionais e aos polímeros non biodegradables porque é bioabsorbible, biodegradable e biocompatible. Xa é amplamente utilizado en case todas as especialidades médicas debido á súa rápida traducibilidad clínica: aplicacións ortopédicas (scaffolds, parafusos bioabsorbibles); aplicacións cardíacas (stents); odontoloxía; cirurxía plástica (suturas, recheos dérmicos, etc.); e sistemas para a liberación de fármacos. Recentemente, o interese polos dispositivos médicos baseados no PLA aumentou drasticamente, xa que é un material adecuado para as tecnoloxías emerxentes, como a impresión 3D. As súas propiedades e a súa baixa temperatura (55-65 °C) de transición vítrea fano deformable a altas temperaturas (190-220 °C) converténdoo nun dos filamentos máis utilizados nesta tecnoloxía, sendo o modelado de deposición fundida (FDM), unha das técnicas máis comúns. O uso da impresión 3D foi ben aceptado no campo biomédico, permitindo a rápida fabricación de estruturas personalizadas con xeometrías complexas e excelente reproducibilidad para penetrarnos na medicina personalizada. Outras estratexias para o desenvolvemento de biomateriales avanzados de gran interese clínico, en particular, orientados á rexeneración do tecido óseo, baséanse na utilización de compostos de fosfato cálcico, como a hidroxiapatita e a incorporación de antibióticos para evitar infeccións postoperatorias. Os antibióticos sistémicos poden provocar reaccións adversas non desexadas, e as concentracións máis altas están limitadas polos perfís de excreción e a vida media dos fármacos. Así pois, un dispositivo biodegradable con antibióticos colocado no niño da infección ou nun lugar con risco podería permitir a administración dun fármaco localizado e específico que pode administrarse a unha concentración máis alta que unha dose sistémica eliminando ou mantendo a infección controlada a medida que se vai reabsorbiendo o dispositivo biodegradable. Por tanto, a combinación de PLA con estes dous materiais en forma de filamento para impresión 3D abren a posibilidade de fabricar de forma personalizada prótese e implantes e axuntando as propiedades e vantaxes de todos os compoñentes nun único dispositivo. Por unha banda, a hidroxiapatita podería mellorar as propiedades mecánicas do PLA, ao concederlle máis rixidez e favorecerían a bioactividad e a osteointegración. Ademais, coa incorporación do antibiótico tamén se podería facer fronte ás infeccións máis recorrentes do tecido óseo, como as causadas por Sthapylococcus aureus. Finalmente, debemos falar da importancia que ten a esterilización, sendo un paso fundamental no proceso de fabricación de calquera biomaterial ou dispositivo médico que vaia a estar en contacto co corpo humano co fin de evitar calquera complicación asociada a eles como as infeccións ou rexeitamentos. As técnicas convencionais de esterilización máis usadas hoxe en día son o vapor e a radiación gamma, pero estas poden presentar certas desvantaxes con algúns materiais termosensibles. Neste sentido, xorde a nova técnica de esterilización mediante CO2 supercrítico que, ao traballar a temperaturas próximas á ambiental, fana unha técnica idónea para biomateriales que se degradan a altas temperaturas, como é o caso do PLA.The aging of the population and associated diseases currently represent a major social and economic challenge, as more and more people require clinical solutions that require the use of implants, prostheses and biomedical devices throughout their lives. In this regard, the growing development of tissue engineering and regenerative medicine brings with it the need for research into advanced and intelligent biomaterials and innovative manufacturing processes. Among these biomaterials, polylactic acid (PLA) composites offer a promising alternative to traditional biomaterials and non-biodegradable polymers because it is bioabsorbable, biodegradable and biocompatible. It is already widely used in almost all medical specialties due to its rapid clinical translatability: orthopedic applications (scaffolds, bioabsorbable screws); cardiac applications (stents); dentistry; plastic surgery (sutures, dermal fillers, etc.); and drug delivery systems. Recently, interest in PLA-based medical devices increased dramatically, as it is a suitable material for emerging technologies such as 3D printing. Its properties and low glass transition temperature (55-65 °C) make it deformable at high temperatures (190-220 °C) making it one of the most widely used filaments in this technology, with fused deposition modeling (FDM) being one of the most common techniques. The use of 3D printing was well accepted in the biomedical field, allowing the rapid fabrication of customized structures with complex geometries and excellent reproducibility to penetrate into personalized medicine. Other strategies for the development of advanced biomaterials of great clinical interest, in particular, aimed at bone tissue regeneration, are based on the use of calcium phosphate compounds such as hydroxyapatite and the incorporation of antibiotics to prevent postoperative infections. Systemic antibiotics can cause unwanted adverse reactions, and higher concentrations are limited by the excretion profiles and half-life of the drugs. Thus, a biodegradable device with antibiotics placed in the nidus of infection or at a site at risk could allow delivery of a targeted, localized drug that can be administered at a higher concentration than a systemic dose eliminating or keeping the infection under control as the biodegradable device is reabsorbed. Therefore, the combination of PLA with these two materials in the form of a 3D printing filament opens up the possibility of manufacturing customized prostheses and implants, combining the properties and advantages of all the components in a single device. On the one hand, hydroxyapatite could improve the mechanical properties of PLA, giving it more rigidity and favoring bioactivity and osseointegration. In addition, the incorporation of the antibiotic could also address the most recurrent infections of bone tissue, such as those caused by Sthapylococcus aureus. Finally, we must talk about the importance of sterilization, being a fundamental step in the manufacturing process of any biomaterial or medical device that is going to be in contact with the human body in order to avoid any complications associated with them such as infections or rejections. The conventional sterilization techniques most commonly used today are steam and gamma radiation, but these may present certain disadvantages with some thermosensitive materials. In this sense, the new technique of sterilization by means of supercritical CO2, which works at temperatures close to the ambient temperature, makes it an ideal technique for biomaterials that degrade at high temperatures, as is the case of PLA

How to sterilize polylactic acid based medical devices?

How sterilization techniques accurately affect the properties of biopolymers continues to be an issue of discussion in the field of biomedical engineering, particularly now with the development of 3D-printed devices. One of the most widely used biopolymers in the manufacture of biomedical devices is the polylactic acid (PLA). Despite the large number of studies found in the literature on PLA devices, relatively few papers focus on the effects of sterilization treatments on its properties. It is well documented in the literature that conventional sterilization techniques, such as heat, gamma irradiation and ethylene oxide, can induced damages, alterations or toxic products release, due to the thermal and hydrolytical sensitivity of PLA. The purposes of this paper are, therefore, to review the published data on the most common techniques used to sterilize PLA medical devices and to analyse how they are affecting their physicochemical and biocompatible properties. Emerging and alternative sterilization methods for sensitive biomaterials are also presented.Xunta de Galicia | Ref. ED481A 2019/314Interreg Atlantic Area | Ref. EAPA_151/201

How to Sterilize Polylactic Acid Based Medical Devices?

How sterilization techniques accurately affect the properties of biopolymers continues to be an issue of discussion in the field of biomedical engineering, particularly now with the development of 3D-printed devices. One of the most widely used biopolymers in the manufacture of biomedical devices is the polylactic acid (PLA). Despite the large number of studies found in the literature on PLA devices, relatively few papers focus on the effects of sterilization treatments on its properties. It is well documented in the literature that conventional sterilization techniques, such as heat, gamma irradiation and ethylene oxide, can induced damages, alterations or toxic products release, due to the thermal and hydrolytical sensitivity of PLA. The purposes of this paper are, therefore, to review the published data on the most common techniques used to sterilize PLA medical devices and to analyse how they are affecting their physicochemical and biocompatible properties. Emerging and alternative sterilization methods for sensitive biomaterials are also presented

Review article laser-induced hyperthermia on graphene oxide composites

Abstract Background Hyperthermia-based therapies have shown great potential for clinical applications such as for the antitumor and antipathogenic activities. Within all strategies, the so-called photothermal therapy proposes to induce the hyperthermia by the remote laser radiation on a photothermal conversion agent, in contact with the target tissue. Methods This paper reviews the most relevant in vitro and in vivo studies focused on NIR laser-induced hyperthermia due to photoexcitation of graphene oxide (GO) and reduced graphene oxide (rGO). Relevant parameters such as the amount of GO/rGO, the influence of the laser wavelength and power density are considered. Moreover, the required temperature and exposure time for each antitumor/antipathogenic case are collected and unified in a thermal dose parameter: the CEM43. Results The calculated CEM43 thermal doses revealed a great variability for the same type of tumor/strain. In order to detect potential tendencies, the values were classified into four ranges, varying from CEM43  60ºC). Conclusions The ability of GO/rGO as effective photothermal conversion agents to promote a controlled hyperthermia is proven. The variability found for the CEM43 thermal doses on the reviewed studies reveals the potentiality to evaluate, for each application, the use of lower temperatures, by modulating time and/or repetitions in the doses

3D printing of PLA:CaP:GO scaffolds for bone tissue applications

13 pages, 8 figures, 1 table.--Open AccessGraphene oxide (GO) has attracted increasing interest for biomedical applications owing to its outstanding properties such as high specific surface area, ability to bind functional molecules for therapeutic purposes and solubility, together with mechanical resistance and good thermal conductivity. The combination of GO with other biomaterials, such as calcium phosphate (CaP) and biodegradable polymers, presents a promising strategy for bone tissue engineering. Presently, the development of these advanced biomaterials benefits from the use of additive manufacturing techniques, such as 3D printing. In this study, we develop a 3D printed PLA:CaP:GO scaffold for bone tissue engineering. First, GO was characterised alone by XPS to determine its main bond contributions and C : O ratio. Secondly, we determined the GO dose which ensures the absence of toxicity, directly exposed in vitro (human osteoblast-like cells MG-63) and in vivo (zebrafish model). In addition, GO was microinjected in the zebrafish to evaluate its effect on immune cells, quantifying the genetic expression of the main markers. Results indicated that the GO tested (C : O of 2.14, 49.50% oxidised, main bonds: C–OH, C–O–C) in a dose ≤0.25 mg mL−1 promoted MG63 cells viability percentages above 70%, and in a dose ≤0.10 mg mL−1 resulted in the absence of toxicity in zebrafish embryos. The immune response evaluation reinforced this result. Finally, the optimised GO dose (0.10 mg mL−1) was combined with polylactic acid (PLA) and CaP to obtain a 3D printed PLA:CaP:GO scaffold. Physicochemical characterisation (SEM/EDS, XRD, FT-Raman, nano-indentation) was performed and in vivo tests confirmed its biocompatibility, enabling a novel approach for bone tissue-related applicationsThis research was financially supported by BIOHEAT project (PID 2020-115415RB-100, Ministerio Ciencia e Innovación España), Xunta de Galicia ED431C 2021/49 and IN607B 2022/13 Program for Consolidación e estructuración de unidades de investigación competitivas (GRC and GPC). Pérez-Davila, S. and Lama, R. are grateful for funding support from Xunta de Galicia pre-doctoral grants (ED481A 2019/314 and IN606A-2017/011, respectively). Universidade de Vigo is acknowledged for funding for the open access chargePeer reviewe