Bioactive Scaffolds Research Articles

Bioinspired poly-dopamine/nano-hydroxyapatite: an upgrading biocompatible coat for 3D-printed polylactic acid scaffold for bone regeneration.

Poly-lactic acid (PLA) has been proposed in dentistry for several regenerative procedures owing to its biocompatibility and biodegradability. However, the presence of methyl groups renders PLA hydrophobic, making the surface less ideal for cell attachment, and it does not promote tissue regeneration. Upgrading PLA with inductive biomaterial is a crucial step to increase the bioactivity of the PLA and allow cellular adhesion. Our purpose is to evaluate biocompatibility, bioactivity, cellular adhesion, and mechanical properties of 3D-printed PLA scaffold coated with poly-dopamine (PDA) and nano-hydroxyapatite (n-HA) versus PLA and PLA/n-HA scaffolds. The fused deposition modelling technique was used to print PLA, PLA with embedded n-HA particles, and PLA scaffold coated with PDA/n-HA by immersion. After matrices characterization for their chemical composition and surface properties, testing the compressive strength was pursued using a universal testing machine. The bioactivity of scaffolds was evaluated by monitoring the formation of calcium phosphate compounds after simulated body fluid immersion. The PLA/PDA/n-HA scaffold showed the highest compressive strength which was 29.11 ± 7.58 MPa with enhancing calcium phosphate crystals deposition with a specific calcium polyphosphate phase formed exclusively on PLA/PDA/n-HA. With cell viability assay, the PDA/n-HA-coated matrix was biocompatible with increase in the IC50, reaching ⁓176.8 at 72 without cytotoxic effect on the mesenchymal stem cells, promoting their adhesion and proliferation evaluated by confocal microscopy. The study explored the biocompatibility, bioactivity, and the cell adhesion ability of PDA/n-HA coat on a 3D-printed PLA scaffold that qualifies its use as a promising regenerative material.

Synthesis, biological evaluation, and DFT analysis of s-triazine analogues with medicinal potential integrated with bioactive heterocyclic scaffolds

This paper introduces a series of novel s-triazine analogues (designated as compounds (14–26) incorporating diverse bioactive heterocyclic scaffolds such as 1-adamantylamine, sulfamerazine, sulfadiazine, morpholine, 2-amino-5-methylthiazole, n-phenylpiperazine, and n-ethyl piperazine. These analogues were meticulously incorporated due to their potential medicinal relevance. Their antimicrobial properties were evaluated against Pseudomonas chlororaphis and Malassezia furfur. Notably, compounds 20 and 26, derived from distinct synthetic schemes, demonstrated the highest activity, with IC50 values of 57.66±0.47 and 17.33±0.47 µg/mL, respectively, against Pseudomonas chlororaphis, and IC50 values of 43.66±0.57 and 37.66±0.57 µg/mL, respectively, against Malassezia furfur. A comprehensive analysis utilizing Density Functional Theory (DFT) was employed to validate the experimental findings. This manuscript encapsulates the synthesis, biological assessment, and computational scrutiny of the novel s-triazine analogues, shedding light on their potential as antimicrobial agents and providing insights into their molecular characteristics. The ADMET analysis showed that the synthesized compounds had pharmacokinetic properties that are potentially suitable for clinical use.

A Multidisciplinary Evaluation of Three-Dimensional Polycaprolactone Bioactive Glass Scaffolds for Bone Tissue Engineering Purposes.

In the development of bone graft substitutes, a fundamental step is the use of scaffolds with adequate composition and architecture capable of providing support in regenerative processes both on the tissue scale, where adequate resistance to mechanical stress is required, as well as at the cellular level where compliant chemical-physical and mechanical properties can promote cellular activity. In this study, based on a previous optimization study of this group, the potential of a three-dimensional construct based on polycaprolactone (PCL) and a novel biocompatible Mg- and Sr-containing glass named BGMS10 was explored. Fourier-transform infrared spectroscopy and scanning electron microscopy showed the inclusion of BGMS10 in the scaffold structure. Mesenchymal stem cells cultured on both PCL and PCL-BGMS10 showed similar tendencies in terms of osteogenic differentiation; however, no significant differences were found between the two scaffold types. This circumstance can be explained via X-ray microtomography and atomic force microscopy analyses, which correlated the spatial distribution of the BGMS10 within the bulk with the elastic properties and topography at the cell scale. In conclusion, our study highlights the importance of multidisciplinary approaches to understand the relationship between design parameters, material properties, and cellular response in polymer composites, which is crucial for the development and design of scaffolds for bone regeneration.

Mechanically robust and personalized silk fibroin-magnesium composite scaffolds with water-responsive shape-memory for irregular bone regeneration

The regeneration of critical-size bone defects, especially those with irregular shapes, remains a clinical challenge. Various biomaterials have been developed to enhance bone regeneration, but the limitations on the shape-adaptive capacity, the complexity of clinical operation, and the unsatisfied osteogenic bioactivity have greatly restricted their clinical application. In this work, we construct a mechanically robust, tailorable and water-responsive shape-memory silk fibroin/magnesium (SF/MgO) composite scaffold, which is able to quickly match irregular defects by simple trimming, thus leading to good interface integration. We demonstrate that the SF/MgO scaffold exhibits excellent mechanical stability and structure retention during the degradative process with the potential for supporting ability in defective areas. This scaffold further promotes the proliferation, adhesion and migration of osteoblasts and the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. With suitable MgO content, the scaffold exhibits good histocompatibility, low foreign-body reactions (FBRs), significant ectopic mineralisation and angiogenesis. Skull defect experiments on male rats demonstrate that the cell-free SF/MgO scaffold markedly enhances bone regeneration of cranial defects. Taken together, the mechanically robust, personalised and bioactive scaffold with water-responsive shape-memory may be a promising biomaterial for clinical-size and irregular bone defect regeneration.

Late-stage diversification of bacterial natural products through biocatalysis.

Bacterial natural products (BNPs) are very important sources of leads for drug development and chemical novelty. The possibility to perform late-stage diversification of BNPs using biocatalysis is an attractive alternative route other than total chemical synthesis or metal complexation reactions. Although biocatalysis is gaining popularity as a green chemistry methodology, a vast majority of orphan sequenced genomic data related to metabolic pathways for BNP biosynthesis and its tailoring enzymes are underexplored. In this review, we report a systematic overview of biotransformations of 21 molecules, which include derivatization by halogenation, esterification, reduction, oxidation, alkylation and nitration reactions, as well as degradation products as their sub-derivatives. These BNPs were grouped based on their biological activities into antibacterial (5), antifungal (5), anticancer (5), immunosuppressive (2) and quorum sensing modulating (4) compounds. This study summarized 73 derivatives and 16 degradation sub-derivatives originating from 12 BNPs. The highest number of biocatalytic reactions was observed for drugs that are already in clinical use: 28 reactions for the antibacterial drug vancomycin, followed by 18 reactions reported for the immunosuppressive drug rapamycin. The most common biocatalysts include oxidoreductases, transferases, lipases, isomerases and haloperoxidases. This review highlights biocatalytic routes for the late-stage diversification reactions of BNPs, which potentially help to recognize the structural optimizations of bioactive scaffolds for the generation of new biomolecules, eventually leading to drug development.

3D-Printed Polycaprolactone-Based Containing Calcium Zirconium Silicate: Bioactive Scaffold for Accelerating Bone Regeneration.

There is an essential clinical need to develop rapid process scaffolds to repair bone defects. The current research presented the development of calcium zirconium silicate/polycaprolactone for bone tissue engineering utilising melt extrusion-based 3D printing. Calcium zirconium silicate (CZS) nanoparticles were added to polycaprolactone (PCL) porous scaffolds to enhance their biological and mechanical properties, while the resulting properties were studied extensively. No significant difference was found in the melting point of the samples, while the crystallisation temperature points of the samples containing bioceramic increased from 36.1 to 40.2 °C. Thermal degradation commenced around 350 °C for all materials. According to our results, increasing the CZS content from 0 to 40 wt.% (PC40) in porous scaffolds (porosity about 55-62%) improved the compressive strength from 2.8 to 10.9 MPa. Furthermore, apatite formation ability in SBF solution increased significantly by enhancing the CZS percentage. According to MTT test results, the viability of MG63 cells improved remarkably (~29%) in PC40 compared to pure PCL. These findings suggest that a 3D-printed PCL/CZS composite scaffold can be fabricated successfully and shows great potential as an implantable material for bone tissue engineering applications.

Modular Microgel-Based Bioassembly Scaffold Induced Chondrogenic and Osteogenic Differentiation of BMSCs.

Bioactive scaffolds capable of simultaneously repairing osteochondral defects remain a big challenge due to the heterogeneity of bone and cartilage. Currently modular microgel-based bioassembly scaffolds are emerged as potential solution to this challenge. Here, microgels based on methacrylic anhydride (MA) and dopamine modified gelatin (GelMA-DA) are loaded with chondroitin sulfate (CS) (the obtained microgel named GC Ms) or bioactive glass (BG) (the obtained microgel named GB Ms), respectively. GC Ms and GB Ms show good biocompatibility with BMSCs, which suggested by the adhesion and proliferation of BMSCs on their surfaces. Specially, GC Ms promote chondrogenic differentiation of BMSCs, while GB Ms promote osteogenic differentiation. Furthermore, the injectable GC Ms and GB Ms are assembled integrally by bottom-up in situ cross-linking to obtain modular microgel-based bioassembly scaffold (GC-GB/HM), which show a distinct bilayer structure and good porous properties and swelling properties. Particularly, the results of in vivo and in vitro experiments show that GC-GB/HM can simultaneously regulate the expression levels of chondrogenic- and osteogenesis-related genes and proteins. Therefore, modular microgel-based assembly scaffold in this work with the ability to promote bidirectional differentiation of BMSCs and has great potential for application in the minimally invasive treatment of osteochondral tissue defects.

ROS-scavenging bioactive scaffold orchestrates bone regeneration for osteoporotic bone defect repair

The repair of osteoporotic bone defects, particularly those with irregular shapes, remains a significant challenge due to insufficient bone regeneration and an abnormal level of reactive oxygen species (ROS), which impairs the balance of bone remodeling. Materials that intrinsically regulate ROS to rebalance the activation of osteoblasts and osteoclasts represent a highly desirable alternative to current grafting strategies for the management of osteoporotic defects. Inspired by the tea polyphenols and natural extracellular matrix of bone tissue, a novel biomimetic composite scaffold, the epichlorohydrin-crosslinked hydroxyethyl cellulose/soy protein isolate/polydopamine-coated hydroxyapatite composite sponge (EHSS/PHA) scaffold was designed to orchestrate bone-forming bone marrow mesenchymal stem cells (BMSCs) and bone-resorbing osteoclasts for the rejuvenation of osteoporotic bone defect repair. Benefiting from the distinctive capabilities of the EHSS/PHA, including scavenging active oxygen and osteoinduction, we found that the EHSS/PHA could inhibit the formation of osteoclasts and promote osteogenesis of BMSCs by up-regulating the ratio of Opg/Rankl and activating the β-catenin signaling pathway in an oxidative stress environment. With its antioxidant ability, osteogenic, and self-deploying capability, EHSS/PHA effectively promoted the repair of tibial defects in osteoporotic rats by removing excess reactive oxygen species at the defect site. Taken together, this work presents the EHSS/PHA with multifunctional properties that provide new insight into osteoporotic bone defects.

One-step soaking strategy toward mechanobiological double-network hydrogel with improving chondrogenesis capacity

Cartilage tissue engineering (CTE) is a promising strategy for addressing the persistent challenges in healing articular cartilage defects in the clinic, aiming to manufacture scaffolds with ideal mechanical characteristics that can provide a conducive microenvironment for the reconstruction or replacement of damaged cartilage defects. Easy operation, excellent mechanical strength, remarkable biocompatibility, and inherent capacity to promote cartilage formation are essential in CTE. This study designed a mechanobiological double-network (DN) hydrogel (KCS-PAA-Mn2+) through a one-step soaking strategy of immersing the composite hydrogel (KCS-PAA) of kartogenin (KGN)-conjugated short-chain chitosan (CS) covalent with polyacrylic acid (PAA) in manganese chloride (MnCl2) solution. Due to the strong physical interactions of CS chain-entanglement network and carboxylate-Mn2+ complex inducing polymer aggregation state transitions, the KCS-PAA-Mn2+ DN hydrogel exhibited exceptional mechanical characteristics, such as high tensile property (strength: 0.24 MPa at a strain of 552 %; toughness: 0.66 MPa), compressibility (strength: 51.98 MPa at a strain of 95 %; compressive modulus: 0.09 MPa), controllable swelling behavior (~327 %), and sustained drug release (>2 weeks). Moreover, in vitro biological studies demonstrated that the KCS-PAA-Mn2+ DN hydrogel not only promoted cell growth and proliferation but also enhanced the expression of genes specific to cartilage and the release of cartilage extracellular matrix (ECM) by bone mesenchymal stem cells (BMSCs), thus enabling a continuous concentration for a long period and persistently enhancing its chondrogenic efficiency. Overall, this soaking methodology reported here is universal to construct mechanically bioactive scaffolds that could expand their bio-applicability with simultaneous advantages of mechanical supports, tailorable swelling, sustainable drug release and long-lasting biological function, thus facilitating the advancement of cartilage-engineered hydrogel biomaterials to a higher level.

Silver-doped glass-ceramic scaffolds with antibacterial and bioactive properties for bone substitution

The preparation of scaffolds that are both macroporous and mechanically strong is a significant challenge in the development of bioactive ceramic materials for bone substitution. Furthermore, the introduction of beneficial extra-functionalities such as bacterial inhibition is highly appealing but adds complexity to implant design and production. In this study, we aimed to fabricate highly porous, bioactive and antibacterial glass-ceramic scaffolds with interconnected macropores through the foam replica method. The scaffolds were sintered at two different temperatures (620 and 850 °C), yielding glassy or partially crystallized materials, respectively. The scaffold produced at higher temperature was found to be highly porous (>75 vol%), mechanically stronger and able to induce hydroxyapatite formation after three days of soaking in SBF (in vitro bioactivity). In order to confer antibacterial activity, silver (Ag) ions were introduced onto the scaffold surface through ion exchange in an aqueous solution. Compositional analysis confirmed the successful doping of the scaffold surface with silver, which was continuously released in SBF for at least 28 days, as revealed by ICP-MS. Finally, the antibacterial action of the Ag-doped scaffold was confirmed towards Staphylococcus epidermidis. Overall, the results reported in this work show the potential of foam-like Ag-doped bioactive glass-ceramic scaffolds to be used in applications requiring bone substitution and antibacterial properties.

Fabrication of poly(xylitol‐citrate‐sebacate) and strontium‐doped mesoporous bioactive glass scaffold for tissue engineering application

AbstractIn this study, strontium‐doped mesoporous bioactive glass nanoparticles (Sr‐MBGNs) were incorporated into a poly(xylitol‐citrate‐sebacate) (PXCS) matrix using solution mixing techniques. The resulting composites, including PXCS, PXCS/1.5% Sr‐MBGNs, PXCS/3% Sr‐MBGNs, and PXCS/5% Sr‐MBGNs, were characterized for biomedical applications using FTIR, DSC, and x‐ray diffraction analyses. High‐resolution scanning electron microscopy (HRSEM) and a universal testing machine were employed to investigate the structure, morphology, and mechanical properties of the polymer and its nanocomposites. Our findings indicate that the introduction of polymer and its nanocomposites minimally affects the glass transition and crystallinity. The observed decrease in glass transition temperature with increasing Sr‐MBGNs content suggests a plasticizing effect. These results are consistent with previous studies. Additionally, in vitro studies were conducted to evaluate antibacterial properties, VERO cell line proliferation, degradation, and swelling percentage of the scaffolds. Metal ions release behavior was assessed using inductively coupled plasma atomic emission spectrometry (ICP‐AES) Furthermore, the drug loading and release of curcumin from PXCS/5% Sr‐MBGNs and PXCS/Sr‐MBGNs nanocomposite scaffolds were investigated at varying pH levels (pH: 5.5, 6.8, and 7.4). Both PXCS/5% Sr‐MBGNs and PXCS/5% Sr‐MBGNs scaffolds demonstrated enhanced biological properties, highlighting their potential for use in bone regeneration approaches.

Rapid spectrophotometric detection for optimized production of landomycins and characterization of their therapeutic potential.

Microbial-derived natural products remain a major source of structurally diverse bioactive compounds and chemical scaffolds that have the potential as new therapeutics to target drug-resistant pathogens and cancers. In particular, genome mining has revealed the vast number of cryptic or low-yield biosynthetic gene clusters in the genus Streptomyces. However, low natural product yields-improvements to which have been hindered by the lack of high throughput methods-have slowed the discovery and development of many potential therapeutics. Here, we describe our efforts to improve yields of landomycins-angucycline family polyketides under investigation as cancer therapeutics-by a genetically modified Streptomyces cyanogenus 136. After simplifying the extraction process from S. cyanogenus cultures, we identified a wavelength at which the major landomycin products are absorbed in culture extracts, which we used to systematically explore culture medium compositions to improve total landomycin titers. Through correlational analysis, we simplified the culture optimization process by identifying an alternative wavelength at which culture supernatants absorb yet is representative of total landomycin titers. Using the subsequently improved sample throughput, we explored landomycin production during the culturing process to further increase landomycin yield and reduce culture time. Testing the antimicrobial activity of the isolated landomycins, we report broad inhibition of Gram-positive bacteria, inhibition of fungi by landomycinone, and broad landomycin resistance by Gram-negative bacteria that is likely mediated by the exclusion of landomycins by the bacterial membrane. Finally, the anticancer activity of the isolated landomycins against A549 lung carcinoma cells agrees with previous reports on other cell lines that glycan chain length correlates with activity. Given the prevalence of natural products produced by Streptomyces, as well as the light-absorbing moieties common to bioactive natural products and their metabolic precursors, our method is relevant to improving the yields of other natural products of interest.

An Enantioselective Aminocatalytic Cascade Reaction Affording Bioactive Hexahydroazulene Scaffolds.

A novel cascade reaction initiated by an enantioselective aminocatalysed 1,3-dipolar [6+4] cycloaddition between catalytically generated trienamines and 3-oxidopyridinium betaines is presented. The [6+4] cycloadduct spontaneously undergoes an intramolecular enamine-mediated aldol, hydrolysis, and E1cb sequence, which ultimately affords a chiral hexahydroazulene framework. In this process, three new C-C bonds and three new stereocenters are formed, enabled by a formal unfolding of the pyridine moiety from the dipolar reagent. The hexahydroazulenes are formed with excellent diastereo-, regio- and periselectivity (>20 : 1), up to 96 % ee, and yields up to 52 %. Synthetic elaborations of this scaffold were performed, providing access to a variety of functionalised hydroazulene compounds, of which some were found to display biological activity in U-2OS osteosarcoma cells in cell painting assays.

Strategically Designed Bifunctional Polydopamine Enwrapping Polycaprolactone-Hydroxyapatite-Doxorubicin Composite Nanofibers for Osteosarcoma Treatment and Bone Regeneration.

This study presents a new multifunctional nanofibrous drug delivery system to provide effective combination therapy with enormous potential for the treatment of osteosarcoma. We developed a composite nanofiber scaffold comprising poly(ε-caprolactone) (PCL) and hydroxyapatite (HAp)-loaded doxorubicin (DOX) coated with polydopamine (PDA) to combine cancer cell inhibition with bone tissue regeneration. DOX was conjugated with HAp and then mixed with a PCL solution to prepare a PCL/HAp-DOX (labeled PCLDH) nanofiber. Then, in situ polymerization of PDA on the PCLDH occurred to produce the PCLDH@PDA composite nanofiber. The morphology, XRD, FT-IR, wettability, photothermal characteristics, cumulative drug release, and in vitro bioactivities were evaluated. We found that the PDA coating not only enhanced the hydrophilic properties but also controlled drug release. The PCLDH@PDA composite scaffold significantly suppressed the proliferation of bone cancer cells initially and, consequently, improved the adhesion and proliferation of human mesenchymal stem cells (hMSCs). The PDA coating boosted the composite scaffold's bioactivity, as demonstrated through ALP activity, ARS assay, and biomineralization results. This strategy offers a promising dual-function scaffold to treat residual cancer and reconstruct defects after osteosarcoma surgery.

Unprecedented Approach of Fabrication and Analysis of a Bioactive PDMS/Hydroxyapatite/Graphene Nanocomposite Scaffold with a Vascular Channel to Combat Carcinogenesis.

In the present investigation, natural bone-derived hydroxyapatite (HA, 2 wt %) and/or exfoliated graphene (Gr, 0.1 wt %)-embedded polydimethylsiloxane (PDMS) elastomeric films were prepared using a vascular method. The morphology, mechanical properties, crystallinity, and chemical structure of the composite films were evaluated. The in vitro biodegradation kinetics of the films indicates their adequate physiological stability. Most of the results favored PDMS/HA/Gr as a best composite scaffold having more than 703% elongation. A simulation study of the microfluidic vascular channel of the PDMS/HA/Gr scaffold suggests that the pressure drop at the outlet became greater (from 1.19 to 0.067 Pa) unlike velocity output (from 0.071 to 0.089 m/s), suggesting a turbulence-free laminar flow. Our bioactive scaffold material, PDMS/HA/Gr, showed highest cytotoxicity toward the lung cancer and breast cancer cells through Runx3 protein-mediated cytotoxic T lymphocyte (CTL) generation. Our data and predicted mechanism also suggested that the PDMS/HA/Gr-supported peripheral blood mononuclear cells (PBMCs) not only increased the generation of CTL but also upregulated the expression of RUNX3. Since the PDMS/HA/Gr scaffold-supported Runx3 induced CTL generation caused maximum cell cytotoxicity of breast cancer (MCF-7) and lung cancer (A549) cells, PDMS/HA/Gr can be treated as an excellent potential candidate for CTL-mediated cancer therapy.

Exosomes endow photocurable 3D printing 45S5 ceramic scaffolds to enhance angiogenesis-osteogenesis coupling for accelerated bone regeneration

The reconstruction of the vascular network is crucial step in bone regeneration. Therefore, effectively modulating angiogenesis-osteogenesis coupling in bone tissue engineering scaffolds is currently an urgent need. In this study, we employed silane coupling agents containing double bonds to modify tetrahedral silicate, resulting in the preparation of a photocurable precursor of 45S5 bioactive glass (PG). PG was utilized as a binding agent for tricalcium phosphate (TCP) powder, and we employed a one-step photocuring 3D printing approach to fabricate PG/TCP (PT) scaffolds. Furthermore, the endothelial progenitor cell-derived exosomes (EPC-exos) was encapsulated by GelMA and anchored onto the PT scaffolds to create exosome-functionalized PT/G@Exos composite scaffolds. In summary, the PT/G@Exos composite scaffold effectively orchestrates the creation of a vascularized bone regeneration microenvironment by releasing EPC-exos, as well as calcium, silicon (Si), and phosphorus (P) elements. This enables an efficient modulation of the angiogenesis-osteogenesis coupling of bioactive scaffolds and accelerates bone regeneration.

Late-stage meta-C-H alkylation of pharmaceuticals to modulate biological properties and expedite molecular optimisation in a single step.

Catalysed C-H activation has emerged as a transformative platform for molecular synthesis and provides new opportunities in drug discovery by late-stage functionalisation (LSF) of complex molecules. Notably, small aliphatic motifs have gained significant interest in medicinal chemistry for their beneficial properties and applications as sp3-rich functional group bioisosteres. In this context, we disclose a versatile strategy with broad applicability for the ruthenium-catalysed late-stage meta-C(sp2)-H alkylation of pharmaceuticals. This general protocol leverages numerous directing groups inherently part of bioactive scaffolds to selectivity install a variety of medicinally relevant bifunctional alkyl units within drug compounds. Our strategy enables the direct modification of unprotected lead structures to quickly generate an array of pharmaceutically useful analogues without resorting to de novo syntheses. Moreover, productive late-stage modulation of key biological characteristics of drug candidates upon remote C-H alkylation proves viable, highlighting the major benefits of our approach to offer in drug development programmes.

Yeast Platforms for Production and Screening of Bioactive Derivatives of Rauwolscine.

Monoterpene indole alkaloids (MIAs) make up a highly bioactive class of metabolites produced by a range of tropical and subtropical plants. The corynanthe-type MIAs are a stereochemically complex subclass with therapeutic potential against a large number of indications including cancer, psychotic disorders, and erectile dysfunction. Here, we report yeast-based cell factories capable of de novo production of corynanthe-type MIAs rauwolscine, yohimbine, tetrahydroalstonine, and corynanthine. From this, we demonstrate regioselective biosynthesis of 4 fluorinated derivatives of these compounds and de novo biosynthesis of 7-chlororauwolscine by coexpression of a halogenase with the biosynthetic pathway. Finally, we capitalize on the ability of these cell factories to produce derivatives of these bioactive scaffolds to establish a proof-of-principle drug discovery pipeline in which the corynanthe-type MIAs are screened for bioactivity on human drug targets, expressed in yeast. In doing so, we identify antagonistic and agonistic behavior against the human adrenergic G protein-coupled receptors ADRA2A and ADRA2B, and the serotonergic receptor 5HT4b, respectively. This study thus demonstrates a proto-drug discovery pipeline for bioactive plant-inspired small molecules based on one-pot biocatalysis of natural and new-to-nature corynanthe-type MIAs in yeast.

Bioactive scaffolds for tissue engineering: A review of decellularized extracellular matrix applications and innovations

AbstractDecellularized extracellular matrix (dECM) offers a three‐dimensional, non‐immunogenic scaffold, enriched with bioactive components, making it a suitable candidate for tissue regeneration. Although dECM‐based scaffolds have been successfully implemented in preclinical and clinical settings within tissue engineering and regenerative medicine, the mechanisms of tissue remodeling and functional restoration are not fully understood. This review critically assesses the state‐of‐the‐art in dECM scaffolds, including decellularization techniques for various tissues, quality control and cross‐linking. It highlights the functional properties of dECM components and their latest applications in multiorgan tissue engineering and biomedicine. Additionally, the review addresses current challenges and limitations of decellularized scaffolds and offers perspectives on future directions in the field.

Enriched mesoporous bioactive glass scaffolds as bone substitutes in critical diaphyseal bone defects in rabbits

In the field of orthopedic surgery, there is an increasing need for the development of bone replacement materials for the treatment of bone defects. One of the main focuses of biomaterials engineering are advanced bioceramics like mesoporous bioactive glasses (MBG´s). The present study compared the new bone formation after 12 weeks of implantation of MBG scaffolds with composition 82,5SiO2–10CaO–5P2O5-x 2.5SrO alone (MBGA), enriched with osteostatin, an osteoinductive peptide, (MBGO) or enriched with bone marrow aspirate (MBGB) in a long bone critical defect in radius bone of adult New Zealand rabbits. New bone formation from the MBG scaffold groups was compared to the gold standard defect filled with iliac crest autograft and to the unfilled defect. Radiographic follow-up was performed at 2, 6, and 12 weeks, and microCT and histologic examination were performed at 12 weeks. X-Ray study showed the highest bone formation scores in the group with the defect filled with autograft, followed by the MBGB group, in addition, the microCT study showed that bone within defect scores (BV/TV) were higher in the MBGO group. This difference could be explained by the higher density of newly formed bone in the osteostatin enriched MBG scaffold group. Therefore, MBG scaffold alone and enriched with osteostatin or bone marrow aspirate increase bone formation compared to defect unfilled, being higher in the osteostatin group. The present results showed the potential to treat critical bone defects by combining MBGs with osteogenic peptides such as osteostatin, with good prospects for translation into clinical practice. Statement of significanceTreatment of bone defects without the capacity for self-repair is a global problem in the field of Orthopedic Surgery, as evidenced by the fact that in the U.S alone it affects approximately 100,000 patients per year. The gold standard of treatment in these cases is the autograft, but its use has limitations both in the amount of graft to be obtained and in the morbidity produced in the donor site. In the field of materials engineering, there is a growing interest in the development of a bone substitute equivalent. Mesoporous bioactive glass (MBG´s) scaffolds with three-dimensional architecture have shown great potential for use as a bone substitutes. The osteostatin-enriched Sr-MBG used in this long bone defect in rabbit radius bone in vivo study showed an increase in bone formation close to autograft, which makes us think that it may be an option to consider as bone substitute.