Photothermal-responsive nanosized hybrid polymersome as versatile therapeutics codelivery nanovehicle for effective tumor suppression.

Effective cancer therapies often demand delivery of combinations of drugs to inhibit multidrug resistance through synergism, and the development of multifunctional nanovehicles with enhanced drug loading and delivery efficiency for combination therapy is currently a major challenge in nanotechnology. However, such combinations are more challenging to administer than single drugs and can require multipronged approaches to delivery. In addition to being stable and biodegradable, vehicles for such therapies must be compatible with both hydrophobic and hydrophilic drugs, and release drugs at sustained therapeutic levels. Here, we report synthesis of porous silicon nanoparticles conjugated with gold nanorods [composite nanoparticles (cNPs)] and encapsulate them within a hybrid polymersome using double-emulsion templates on a microfluidic chip to create a versatile nanovehicle. This nanovehicle has high loading capacities for both hydrophobic and hydrophilic drugs, and improves drug delivery efficiency by accumulating at the tumor after i.v. injection in mice. Importantly, a triple-drug combination suppresses breast tumors by 94% and 87% at total dosages of 5 and 2.5 mg/kg, respectively, through synergy. Moreover, the cNPs retain their photothermal properties, which can be used to significantly inhibit multidrug resistance upon near-infrared laser irradiation. Overall, this work shows that our nanovehicle has great potential as a drug codelivery nanoplatform for effective combination therapy that is adaptable to other cancer types and to molecular targets associated with disease progression.

Cellular Internalization-Induced Aggregation of Porous Silicon Nanoparticles for Ultrasound Imaging and Protein-Mediated Protection of Stem Cells.

Nanotechnology employs multifunctional engineered materials in the nanoscale range that provides many opportunities for translational stem cell research and therapy. Here, a cell-penetrating peptide (virus-1 transactivator of transcription)-conjugated, porous silicon nanoparticle (TPSi NP) loaded with the Wnt3a protein to increase both the cell survival rate and the delivery precision of stem cell transplantation via a combinational theranostic strategy is presented. The TPSi NP with a pore size of 10.7 nm and inorganic framework enables high-efficiency loading of Wnt3a, prolongs Wnt3a release, and increases antioxidative stress activity in the labeled mesenchymal stem cells (MSCs), which are highly beneficial properties for cell protection in stem cell therapy for myocardial infarction. It is confirmed that the intracellular aggregation of TPSi NPs can highly amplify the acoustic scattering of the labeled MSCs, resulting in a 2.3-fold increase in the ultrasound (US) signal compared with that of unlabeled MSCs. The translational potential of the designed nanoagent for real-time US imaging-guided stem cell transplantation is confirmed via intramyocardial injection of labeled MSCs in a nude mouse model. It is proposed that the intracellular aggregation of protein drug-loaded TPSi NPs could be a simple but robust strategy for improving the therapeutic effect of stem cell therapy.

Gold Nanorods Conjugated Porous Silicon Nanoparticles Encapsulated in Calcium Alginate Nano Hydrogels Using Microemulsion Templates.

Porous silicon nanoparticles (PSiNPs) and gold nanorods (AuNRs) can be used as biocompatible nanocarriers for delivery of therapeutics but undesired leakage makes them inefficient. By encapsulating the PSiNPs and AuNRs in a hydrogel shell, we create a biocompatible functional nanocarrier that enables sustained release of therapeutics. Here, we report the fabrication of AuNRs-conjugated PSi nanoparticles (AuNRsPSiNPs) through two-step chemical reaction for high-capacity loading of hydrophobic and hydrophilic therapeutics with photothermal property. Furthermore, using water-in-oil microemulsion templates, we encapsulate the AuNRsPSiNPs within a calcium alginate hydrogel nanoshell, creating a versatile biocompatible nanocarrier to codeliver therapeutics for biomedical applications. We find that the functionalized nanohydrogel effectively controls the release rate of the therapeutics while maintaining a high loading efficiency and tunable loading ratios. Notably, combinations of therapeutics coloaded in the functionalized nanohydrogels significantly enhance inhibition of multidrug resistance through synergism and promote faster cancer cell death when combined with photothermal therapy. Moreover, the AuNRs can mediate the conversion of near-infrared laser radiation into heat, increasing the release of therapeutics as well as thermally inducing cell damage to promote faster cancer cell death. Our AuNRsPSiNPs functionalized calcium alginate nanohydrogel holds great promise for photothermal combination therapy and other advanced biomedical applications.

Engineered Multifunctional Albumin-Decorated Porous Silicon Nanoparticles for FcRn Translocation of Insulin.

The last decade has seen remarkable advances in the development of drug delivery systems as alternative to parenteral injection-based delivery of insulin. Neonatal Fc receptor (FcRn)-mediated transcytosis has been recently proposed as a strategy to increase the transport of drugs across the intestinal epithelium. FcRn-targeted nanoparticles (NPs) could hijack the FcRn transcytotic pathway and cross the epithelial cell layer. In this study, a novel nanoparticulate system for insulin delivery based on porous silicon NPs is proposed. After surface conjugation with albumin and loading with insulin, the NPs are encapsulated into a pH-responsive polymeric particle by nanoprecipitation. The developed NP formulation shows controlled size and homogeneous size distribution. Transmission electron microscopy (TEM) images show successful encapsulation of the NPs into pH-sensitive polymeric particles. No insulin release is detected at acidic conditions, but a controlled release profile is observed at intestinal pH. Toxicity studies show high compatibility of the NPs with intestinal cells. In vitro insulin permeation across the intestinal epithelium shows approximately fivefold increase when insulin is loaded into FcRn-targeted NPs. Overall, these FcRn-targeted NPs offer a toolbox in the development of targeted therapies for oral delivery of insulin.

Novel delivery systems for improving the clinical use of peptides.

Peptides have long been recognized as a promising group of therapeutic substances to treat various diseases. Delivery systems for peptides have been under development since the discovery of insulin for the treatment of diabetes. The challenge of using peptides as drugs arises from their poor bioavailability resulting from the low permeability of biological membranes and their instability. Currently, subcutaneous injection is clinically the most common administration route for peptides. This route is cost-effective and suitable for self-administration, and the development of appropriate dosing equipment has made performing the repeated injections relatively easy; however, only few clinical subcutaneous peptide delivery systems provide sustained peptide release. As a result, frequent injections are needed, which may cause discomfort and additional risks resulting from a poor administration technique. Controlled peptide delivery systems, able to provide required therapeutic plasma concentrations over an extended period, are needed to increase peptide safety and patient compliancy. In this review, we summarize the current peptidergic drugs, future developments, and parenteral peptide delivery systems. Special emphasis is given to porous silicon, a novel material in peptide delivery. Biodegradable and biocompatible porous silicon possesses some unique properties, such as the ability to carry exceptional high peptide payloads and to modify peptide release extensively. We have successfully developed porous silicon as a carrier material for improved parenteral peptide delivery. Nanotechnology, with its different delivery systems, will enable better use of peptides in several therapeutic applications in the near future.

Core/Shell Nanocomposites Produced by Superfast Sequential Microfluidic Nanoprecipitation.

Although a number of techniques exist for generating structured organic nanocomposites, it is still challenging to fabricate them in a controllable, yet universal and scalable manner. In this work, a microfluidic platform, exploiting superfast (milliseconds) time intervals between sequential nanoprecipitation processes, has been developed for high-throughput production of structured core/shell nanocomposites. The extremely short time interval between the sequential nanoprecipitation processes, facilitated by the multiplexed microfluidic design, allows us to solve the instability issues of nanocomposite cores without using any stabilizers. Beyond high throughput production rate (∼700 g/day on a single device), the generated core/shell nanocomposites harness the inherent ultrahigh drug loading degree and enhanced payload dissolution kinetics of drug nanocrystals and the controlled drug release from polymer-based nanoparticles.

Drug-Loaded Multifunctional Nanoparticles Targeted to the Endocardial Layer of the Injured Heart Modulate Hypertrophic Signaling.

Ischemic heart disease is the leading cause of death globally. Severe myocardial ischemia results in a massive loss of myocytes and acute myocardial infarction, the endocardium being the most vulnerable region. At present, current therapeutic lines only ameliorate modestly the quality of life of these patients. Here, an engineered nanocarrier is reported for targeted drug delivery into the endocardial layer of the left ventricle for cardiac repair. Biodegradable porous silicon (PSi) nanoparticles are functionalized with atrial natriuretic peptide (ANP), which is known to be expressed predominantly in the endocardium of the failing heart. The ANP-PSi nanoparticles exhibit improved colloidal stability and enhanced cellular interactions with cardiomyocytes and non-myocytes with minimal toxicity. After confirmation of good retention of the radioisotope 111-Indium in relevant physiological buffers over 4 h, in vivo single-photon emission computed tomography (SPECT/CT) imaging and autoradiography demonstrate increased accumulation of ANP-PSi nanoparticles in the ischemic heart, particularly in the endocardial layer of the left ventricle. Moreover, ANP-PSi nanoparticles loaded with a novel cardioprotective small molecule attenuate hypertrophic signaling in the endocardium, demonstrating cardioprotective potential. These results provide unique insights into the development of nanotherapies targeted to the injured region of the myocardium.

Coating Nanoparticles with Plant-Produced Transferrin-Hydrophobin Fusion Protein Enhances Their Uptake in Cancer Cells.

The encapsulation of drugs to nanoparticles may offer a solution for targeted delivery. Here, we set out to engineer a self-assembling targeting ligand by combining the functional properties of human transferrin and fungal hydrophobins in a single fusion protein. We showed that human transferrin can be expressed in Nicotiana benthamiana plants as a fusion with Trichoderma reesei hydrophobins HFBI, HFBII, or HFBIV. Transferrin-HFBIV was further expressed in tobacco BY-2 suspension cells. Both partners of the fusion protein retained their functionality; the hydrophobin moiety enabled migration to a surfactant phase in an aqueous two-phase system, and the transferrin moiety was able to reversibly bind iron. Coating porous silicon nanoparticles with the fusion protein resulted in uptake of the nanoparticles in human cancer cells. This study provides a proof-of-concept for the functionalization of hydrophobin coatings with transferrin as a targeting ligand.

Preparation and biological evaluation of ethionamide-mesoporous silicon nanoparticles against Mycobacterium tuberculosis.

Ethionamide (ETH) is an important second-line antituberculosis drug used for the treatment of patients infected with multidrug-resistant Mycobacterium tuberculosis. Recently, we reported that the loading of ETH into thermally carbonized-porous silicon (TCPSi) nanoparticles enhanced the solubility and permeability of ETH at different pH-values and also increased its metabolization process. Based on these results, we synthesized carboxylic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) conjugated with ETH and its antimicrobial effect was evaluated against Mycobacterium tuberculosis strain H37Rv. The activity of the conjugate was increased when compared to free-ETH, which suggests that the nature of the synergy between the NPs and ETH is likely due to the weakening of the bacterial cell wall that improves conjugate-penetration. These ETH-conjugated NPs have great potential in reducing dosing frequency of ETH in the treatment of multidrug-resistant tuberculosis (MDR-TB).

Regenerative Electroless Etching of Silicon.

Regenerative electroless etching (ReEtching), described herein for the first time, is a method of producing nanostructured semiconductors in which an oxidant (Ox1 ) is used as a catalytic agent to facilitate the reaction between a semiconductor and a second oxidant (Ox2 ) that would be unreactive in the primary reaction. Ox2 is used to regenerate Ox1 , which is capable of initiating etching by injecting holes into the semiconductor valence band. Therefore, the extent of reaction is controlled by the amount of Ox2 added, and the rate of reaction is controlled by the injection rate of Ox2 . This general strategy is demonstrated specifically for the production of highly luminescent, nanocrystalline porous Si from the reaction of V2 O5 in HF(aq) as Ox1 and H2 O2 (aq) as Ox2 with Si powder and wafers.

Influence of Surface Chemistry on Ibuprofen Adsorption and Confinement in Mesoporous Silicon Microparticles.

The effect of adsorption and confinement on ibuprofen was studied by immersion loading the molecules into porous silicon (PSi) microparticles. The PSi microparticles were modified into thermally oxidized PSi (TOPSi) and thermally hydrocarbonized PSi (THCPSi) to evaluate the effects of the loading solvent and the surface chemistry on the obtainable drug payloads. The payloads, location, and the molecular state of the adsorbed drug were evaluated using thermal analysis. The results showed that after the adsorption of ∼800 mg/cm3 (wdrug/vpores) of drug into the mesopores, depending on the solvent used in the immersion, the drug began to rapidly recrystallize on the external surface of the particles. Moderate concentrations, however, enabled payloads of 800-850 mg/cm3 without excessive surface crystallization, and thus, there was no need for rinsing the samples to remove the externally crystallized portion. The results showed that the confined ibuprofen forms nanocrystals inside of the mesopores after approximately 200 mg/cm3 payloads were obtained, accounting for half of the adsorbed drug amount. The presence of both crystalline and noncrystalline phases was further characterized using variable temperature solid-state nuclear magnetic resonance (NMR) measurements. The interactions between the drug molecules and the pore walls of TOPSi and THCPSi were observed using Fourier transform infrared and 1H NMR spectroscopies, and the hydrogen bonding between the silanol groups of TOPSi and the adsorbed ibuprofen was confirmed, but having only limited effect on the overall state of the confined drug. In vitro drug permeation studies in Caco-2 and Caco-2/HT29 cocultures showed that the adsorption onto hydrophilic or hydrophobic PSi microparticles had no significant effects on the ibuprofen permeation, whether the drug was partially nanocrystalline or completely in a liquidlike state.

Controlled Dissolution of Griseofulvin Solid Dispersions from Electrosprayed Enteric Polymer Micromatrix Particles: Physicochemical Characterization and in Vitro Evaluation.

The oral bioavailability of a poorly water-soluble drug is often inadequate for the desired therapeutic effect. The bioavailability can be improved by enhancing the physicochemical properties of the drug (e.g., dissolution rate, permeation across the gastrointestinal tract). Other approach include shielding the drug from the gastric metabolism and targeted drug release to obtain optimal drug absorption. In this study, a poorly water-soluble model drug, griseofulvin, was encapsulated as disordered solid dispersions into Eudragit L 100-55 enteric polymer micromatrix particles, which were produced by electrospraying. Similar micromatrix particles were also produced with griseofulvin-loaded thermally oxidized mesoporous silicon (TOPSi) nanoparticles dispersed to the polymer micromatrices. The in vitro drug dissolution at pH 1.2 and 6.8, and permeation at pH 7.4 across Caco-2/HT29 cell monolayers from the micromatrix particles, were investigated. The micromatrix particles were found to be gastro-resistant, while at pH 6.8 the griseofulvin was released very rapidly in a fast-dissolving form. Compared to free griseofulvin, the permeability of encapsulated griseofulvin across the intestinal cell monolayers was greatly improved, particularly for the TOPSi-doped micromatrix particles. The griseofulvin solid dispersions were stable during storage for 6 months at accelerated conditions. Overall, the method developed here could prove to be a useful oral drug delivery solution for improving the bioavailability of poorly water-soluble or otherwise problematic drugs.

Electrostatic interaction on loading of therapeutic peptide GLP-1 into porous silicon nanoparticles.

Porous silicon (PSi) nanoparticles' tunable properties are facilitating their use at highly challenging medical tasks such as peptide delivery. Because of many different mechanisms that are affecting the interaction between the peptide and the particle, the drug incorporation into the mesoporous delivery system is not straightforward. We have studied the adsorption and loading of incretin hormone glucagon like peptide 1 (GLP-1) on PSi nanoparticles. The results show that the highest loading degree can be achieved in pH values near the isoelectric point of peptide, and the phenomenon is independent of the surface's zeta potential. In order to study the interaction between the peptide and the nanoparticle, we studied the adsorption with lower concentrations and noticed that also non-Coulombic forces have a big role in adsorption of GLP-1. Adsorption is effective and pH-independent especially on low peptide concentrations and onto more hydrophobic nanoparticles. Reversibility of adsorption was studied as a function of buffer pH. When the loading is compared to the total mass of the formulation, the loading degree is 29%, and during desorption experiments 25% is released in 4 h and can be considered as a reversible loading degree. Thus, the peptides adsorbed first seem to create irreversibly adsorbed layer that facilitates reversible adsorption of following peptides.

Processing of pharmaceutical materials by electrospraying under reduced pressure.

CONTEXT: Electrospraying was used in drug particle production. OBJECTIVE: The aim of the research was to evaluate the possibilities to produce drug particles with desired pharmaceutical properties by electrospraying. In particular, the effect of drying pressure on particle properties was studied. MATERIALS AND METHODS: A poorly water soluble model drug (budesonide) was dissolved in chloroform, and the solution was atomized by electrospraying. Following this, the charged droplets were neutralized and dried in a drying chamber. The pressure in the drying chamber was varied. The dried particles were collected and analyzed. RESULTS: The pressure reduction had a slight impact on particle size distribution. The particles produced in reduced pressure turned out to be notably more porous than the particles produced in atmospheric pressure. The pressure reduction also affects the degree of crystallinity of the product. The dissolution of the particles produced in reduced pressures was faster to a certain extent than that of the particles produced in atmospheric pressure. DISCUSSION AND CONCLUSIONS: A setup for electrospraying materials in a reduced pressure was presented. The pressure reduction had a notable impact on particle morphology. The possibilities to tailor the particle properties during electrospraying were studied.

Microfluidic assembly of monodisperse multistage pH-responsive polymer/porous silicon composites for precisely controlled multi-drug delivery.

We report an advanced drug delivery platform for combination chemotherapy by concurrently incorporating two different drugs into microcompoistes with ratiometric control over the loading degree. Atorvastatin and celecoxib were selected as model drugs due to their different physicochemical properties and synergetic effect on colorectal cancer prevention and inhibition. To be effective in colorectal cancer prevention and inhibition, the produced microcomposite contained hypromellose acetate succinate, which is insoluble in acidic conditions but highly dissolving at neutral or alkaline pH conditions. Taking advantage of the large pore volume of porous silicon (PSi), atorvastatin was firstly loaded into the PSi matrix, and then encapsulated into the pH-responsive polymer microparticles containing celecoxib by microfluidics in order to obtain multi-drug loaded polymer/PSi microcomposites. The prepared microcomposites showed monodisperse size distribution, multistage pH-response, precise ratiometric controlled loading degree towards the simultaneously loaded drug molecules, and tailored release kinetics of the loaded cargos. This attractive microcomposite platform protects the payloads from being released at low pH-values, and enhances their release at higher pH-values, which can be further used for colon cancer prevention and treatment. Overall, the pH-responsive polymer/PSi-based microcomposite can be used as a universal platform for the delivery of different drug molecules for combination therapy.

In vivo evaluation of porous silicon and porous silicon solid lipid nanocomposites for passive targeting and imaging.

The use of nanoparticle carriers for the sustained release of cytotoxic drugs in cancer therapy can result in fewer adverse effects and can thus be of great benefit for the patient. Recently, a novel nanocomposite, prepared by the encapsulation of THCPSi nanoparticles within solid lipids (SLN), was developed and characterized as a promising drug delivery carrier in vitro. The present study describes the in vivo evaluation of unmodified THCPSi nanoparticles and THCPSi-solid lipid nanocomposites (THCPSi-SLNCs) as potential drug delivery carriers for cancer therapy by using (18)F radiolabeling for the detection of the particle biodistribution in mice. Passive tumor targeting of (18)F-THCPSis and (18)F-THCPSi-SLNCs by the enhanced permeation and retention effect was investigated in a murine breast cancer model. Encapsulation of THCPSi nanoparticles with solid lipids improved their accumulation in tumors at a 7 week time point (tumor-to-liver ratio 0.10 ± 0.08 and 0.24 ± 0.09% for (18)F-THCPSis and (18)F-THCPSi-SLNCs, respectively).

Confinement effects on drugs in thermally hydrocarbonized porous silicon.

Thermally hydrocarbonized porous silicon (THCPSi) microparticles were loaded with indomethacin (IMC) and griseofulvin (GSV) using three different payloads between 6.2-19.5 and 6.2-11.4 wt %, respectively. The drug loading parameters were selected to avoid crystallization of the drug molecules on the external surface of the particles that would block the pore entrances. The successfulness of the loadings was verified with TG, DSC, and XRPD measurements. The effects of the confinement of IMC and GSV into the small mesopores of THCPSi were analyzed with helium pycnometry, FTIR, and NMR spectroscopy. The results showed the density of the THCPSi loaded drugs to be ca. 10% lower than the bulk crystalline forms, while a melt quenched amorphous drugs showed a density reduction of 3-7.5%. DSC and FTIR results confirmed that the drugs reside in an amorphous form within the THCPSi pores. Similar results were obtained with NMR, which also indicated that IMC may reside as both amorphous clusters and individual molecules within the pores. The (1)H transverse relaxation times (T2) of amorphous and THCPSi loaded drugs showed IMC relaxation times of 0.28 ms for both the cases, whereas for GSV the values were 0.32 and 0.39 ms, respectively, indicating similar limited mobility in both cases. The results indicated that strong drug-carrier interactions were not necessary for stabilizing the amorphous state of the adsorbed drug. Dissolution tests using biorelevant media, fasted state simulated intestinal fluid (FaSSIF) and simulated gastric fluid (SGF), showed that THCPSi-loaded IMC and GSV were rapidly released in FaSSIF with comparable rates to the amorphous forms, whereas in SGF the THCPSi reduced the pH dependency in the dissolution of IMC.

Poly(methyl vinyl ether-alt-maleic acid)-functionalized porous silicon nanoparticles for enhanced stability and cellular internalization.

Currently, developing a stable nanocarrier with high cellular internalization and low toxicity is a key bottleneck in nanomedicine. Here, we have developed a successful method to covalently conjugate poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) copolymer on the surface of (3-aminopropyl)triethoxysilane-functionalized thermally carbonized porous silicon nanoparticles (APSTCPSi NPs), forming a surface negatively charged nanovehicle with unique properties. This polymer conjugated NPs could modify surface smoothness, charge, and hydrophilicity of the developed NPs, leading to considerable improvement in the colloidal and plasma stabilities via enhanced suspensibility and charge repulsion. Furthermore, despite the surface negative charge of the polymer-conjugated NPs, the cellular internalization was increased in both MDA-MB-231 and MCF-7 breast cancer cells. These results provide a proof-of-concept evidence that such polymer-based PSi nanocomposite can be extensively used as a promising candidate for intracellular drug delivery.

Appendicolith classification: physical and chemical properties of appendicoliths in patients with CT diagnosed acute appendicitis - a prospective cohort study.

OBJECTIVE: Appendicoliths are associated with a more complicated course of acute appendicitis and failure of non-operative treatment. We aimed to update the appendicolith classification originally described in 1966 and to assess the association of appendicolith characteristics with appendicitis severity. DESIGN: This prospective predefined MAPPAC-trial (ClinicalTrials.gov NCT03257423) substudy included patients with CT diagnosed appendicitis presenting with an appendicolith. CT visible appendicoliths were harvested at surgery, measured and characterised by morphological examination complemented with micro-CT and micro-X-ray fluorescence spectroscopy. Patients were categorised into two groups: appendicolith appendicitis without other complications and appendicolith appendicitis with complications (appendiceal gangrene, perforation and/or abscess). The association of appendicolith classification and characteristics with appendicitis severity was evaluated. RESULTS: Of 78 patients with a CT appendicolith, 41 appendicoliths were collected and classified based on the degree of hardness into three classes. The hardest appendicoliths (class 3) were less common (19.5%) presenting with a stone-hard outer layer and concentrically layered inner structure around a core. The layered inner structure was also observed in class 2 appendicoliths, but was absent in soft, class 1 appendicoliths. Appendicolith hardness or measures (maximum length, diameter and weight) were not associated with appendicitis severity. The spatial distribution of the main inorganic elements of calcium and phosphorus varied within most appendicoliths. CONCLUSION: This updated classification confirms categorisation of CT visible appendicoliths into three classes based on their physical and chemical characteristics. The data on clinical and aetiopathological characteristics of appendicoliths is scarce and using this systematic classification would add to this understanding.

Lithiated porous silicon nanowires stimulate periodontal regeneration.

Periodontal disease is a significant burden for oral health, causing progressive and irreversible damage to the support structure of the tooth. This complex structure, the periodontium, is composed of interconnected soft and mineralised tissues, posing a challenge for regenerative approaches. Materials combining silicon and lithium are widely studied in periodontal regeneration, as they stimulate bone repair via silicic acid release while providing regenerative stimuli through lithium activation of the Wnt/ß-catenin pathway. Yet, existing materials for combined lithium and silicon release have limited control over ion release amounts and kinetics. Porous silicon can provide controlled silicic acid release, inducing osteogenesis to support bone regeneration. Prelithiation, a strategy developed for battery technology, can introduce large, controllable amounts of lithium within porous silicon, but yields a highly reactive material, unsuitable for biomedicine. This work debuts a strategy to lithiate porous silicon nanowires (LipSiNs) which generates a biocompatible and bioresorbable material. LipSiNs incorporate lithium to between 1% and 40% of silicon content, releasing lithium and silicic acid in a tailorable fashion from days to weeks. LipSiNs combine osteogenic, cementogenic and Wnt/ß-catenin stimuli to regenerate bone, cementum and periodontal ligament fibres in a murine periodontal defect.