Scaffolds For Bone Tissue Engineering Research Articles

Determining the Permeability of Porous Bioceramic Scaffolds: Significance, Overview of Current Methods and Challenges Ahead

The “architectural suitability” of scaffolds for bone tissue engineering is commonly evaluated by assessing the pore volume and the mean pore size (or pore size distribution, if possible) and comparing these values with the reference ranges of human cancellous bone. However, these two parameters cannot precisely describe the complex architecture of bone scaffolds and just provide a preliminary comparative criterion. Permeability is suggested as a more comprehensive and significant parameter to characterize scaffold architecture and mass transport capability, being also related to bone in-growth and, thus, functional properties. However, assessing the permeability of bioactive ceramics and glass scaffolds is a complex task from both methodological and experimental viewpoints. After providing an overview of the fundamentals about porosity in scaffolds, this review explores the different experimental and numerical approaches used to determine the permeability of porous bioceramics, describing the methodologies used (pump-based, gravity-based, acoustic and computational methods) and highlighting advantages and limitations to overcome (e.g., reliability issues and need for better standardization of the experimental procedures).

A Review on Advances and Challenges in Core-Shell Scaffolds for Bone Tissue Engineering: Design, Fabrication, and Clinical Translation.

This review explores core-shell scaffolds in bone tissue engineering, highlighting their osteoconductive and osteoinductive properties critical for bone growth and regeneration. Key design factors include material selection, porosity, mechanical strength, biodegradation kinetics, and bioactivity. Electrospun core-shell nanofibrous scaffolds demonstrate potential in delivering therapeutic agents and enhancing bone regeneration. Critical characterization techniques include structural, surface, chemical composition, mechanical, and degradation analyses. Scaling up production poses challenges, addressed by innovative electrospinning techniques. Future research focuses on regulatory and commercial considerations, while exploring advanced materials and fabrication methods to optimize scaffold performance for improved clinical outcomes.

The induction of bone formation by 3D-printed PLGA microsphere scaffolds in a calvarial orthotopic mouse model: a pilot study.

Polymeric biodegradable microspheres are readily utilized to support targeted drug delivery for various diseases clinically. 3D printed tissue engineering scaffolds from polymer filaments with embedded microspheres or nanoparticles, as well as bulk microsphere scaffolds, have been investigated for regenerative medicine and tissue engineering. However, 3D printed scaffolds consisting only of a homogenous microsphere size with an optimized architecture that includes a unique micro- and macroporosity, have been challenging to produce and hence, have not been assessed in the literature yet. Utilizing our recently established 3D-MultiCompositional Microsphere-Adaptive Printing (3D-McMap) method, the present study evaluated the effectiveness of 3D-printed poly (lactic-co-glycolic acid) (PLGA) microsphere scaffolds, consisting of microsphere sizes 50, 100, or 200μm, on the induction of bone formation when implanted in the calvarial murine regeneration model. Our results showed that PLGA microsphere scaffolds possess unique properties that support bone regeneration by supporting osteoconduction and stimulating, in our opinion, true spontaneous osteoinduction. The study demonstrated that PLGA microsphere-based scaffolds support bone growth in the absence of additional growth factors and promote osteogenesis primarily via their unique geometric configuration. The larger the microspheres were, the greater de novo bone formation was. This proves that bone tissue engineering scaffolds 3D printed from microspheres, enabled by the 3D-McMap method, are superior over bulk material printed scaffolds, as they possess the unique capability of spontaneous induction of new bone formation. With the addition of encapsulated modulatory bone-forming biomolecules they can substantially improve the spatiotemporal control of tissue morphogenesis, potentially leading to new innovative clinical tissue repair therapies that regenerate bone in large defects correctly and fully.

Plant-based scaffolds and osteogenesis: A systematic review.

To enhance the understanding and usefulness of decellularised plant tissues as scaffolds for bone tissue engineering, and to review the recent advances in plant-based scaffolds for bone regeneration. The systematic review was conducted from February to June 2022, and comprised literature search on PubMed and Science Direct databases for articles published in the English language between 2013 and June, 2022. The search was conducted using key words 'plant-based scaffolds and osteogenesis' and 'decellularised plant and scaffolds and bone tissue engineering' and 'plant root-based scaffold and bone formation'. Full-text articles and short communication covering both in vitro and in vivo studies focussing on plant-based scaffolds for osteogenesis were included. Additional references that satisfied the inclusion criteria were found on Google Scholar and included in the review. Quality evaluation of the studies included was done independently by two researchers, and the risk of bias was calculated and categorised as low, medium and high risk. Of the 564 articles, 10(1.77 %) were included; 6(60%) purely in vitro studies, and 4(40%) studies having both in vitro and in vivo components. Decellularized plant tissue alone was used as three-dimensional scaffold materials in 5(50%) studies, but in 4(40%) studies, plant-based composite scaffolds were used. The risk of bias was medium in 7(70%) studies. Plant-based scaffolds promote osteogenesis, but more in vivo research on plant-based studies is needed to label it as suitable scaffolds for bone tissue engineering.

Applications of hydroxyapatite-based polymeric scaffolds in bone tissue engineering: An update

Bone tissue is a comprising of an organic and inorganic environment, in which the collagen element and the mineral part are structured into complex and spongy constructions. Hydroxyapatite (HAp) is the chief inorganic constituent of human bone. HAp is extensively utilized in bone tissue regeneration for its bioactivity and biocompatibility, and a rising number of investigators are discovering ways to recover the physical belongings and biological roles of HAp. However, this biomimetic material has poor mechanical properties, such as low tensile and compressive strength, which make it not suitable for bone tissue engineering (BTE). For this reason, HA is frequently utilized in a mixture with diverse polymers to increase their mechanical strengths and the general performance of the implantable biomaterials advanced for orthopedic usage. In this review, we attempt to contribute a brief and inclusive outline of HAp-based natural and synthetic polymer materials as reinforcing components and their applications in bone tissue engineering.

Dual-Function Femtosecond Laser: β-TCP Structuring and AgNP Synthesis via Photoreduction with Azorean Green Tea for Enhanced Osteointegration and Antibacterial Properties.

β-Tricalcium phosphate (β-TCP) is a well-established biomaterial for bone regeneration, highly regarded for its biocompatibility and osteoconductivity. However, its clinical efficacy is often compromised by susceptibility to bacterial infections. In this study, we address this limitation by integrating femtosecond (fs)-laser processing with the concurrent synthesis of silver nanoparticles (AgNPs) mediated by Azorean green tea leaf extract (GTLE), which is known for its rich antioxidant and anti-inflammatory properties. The fs laser was employed to modify the surface of β-TCP scaffolds by varying scanning velocities, fluences, and patterns. The resulting patterns, formed at lower scanning velocities, display organized nanostructures, along with enhanced roughness and wettability, as characterized by Scanning Electron Microscopy (SEM), optical profilometry, and contact angle measurements. Concurrently, the femtosecond laser facilitated the photoreduction of silver ions in the presence of GTLE, enabling the efficient synthesis of small, spherical AgNPs, as confirmed by UV-vis spectroscopy, Transmission Electron Microscopy (TEM), and Fourier Transform Infrared Spectroscopy (FTIR). The resulting AgNP-embedded β-TCP scaffolds exhibited a significantly improved cell viability and elongation of human bone marrow mesenchymal stem cells (hBM-MSCs), alongside significant antibacterial activity against Staphylococcus aureus (S. aureus). This study underscores the transformative potential of combining femtosecond laser surface modification with GTLE-mediated AgNP synthesis, presenting a novel and effective strategy for enhancing the performance of β-TCP scaffolds in bone-tissue engineering.

Direct MultiSearch optimization of TPMS scaffolds for bone tissue engineering

BackgroundScaffolds designed for tissue engineering must consider multiple parameters, namely the permeability of the design and the wall shear stress experienced by the cells on the scaffold surface. However, these parameters are not independent from each other, with changes that improve wall shear stress, negatively impacting permeability and vice versa. This study introduces a novel multi-objective optimization framework using Direct MultiSearch (DMS) to design triply periodic minimal surface (TPMS) scaffolds for bone tissue engineering. MethodThe optimization algorithm focused on maximizing the permeability of the scaffolds and obtaining a desired value of average wall shear stress (which ranges between the values that promote osteogenic differentiation of 0.1 mPa and 10 mPa). Multiple fluid inlet velocities and target wall shear stress were analyzed. The DMS method successfully generated Pareto fronts for each configuration, enabling the selection of optimized scaffolds based on specific structural requirements. ResultsThe findings reveal that increasing the target wall shear stress results in a greater number of non-dominated points on the Pareto front, highlighting a more robust optimization process. Additionally, it was also demonstrated that the tested Schwartz diamond scaffolds had a better permeability-wall shear stress relation when compared to Schoen gyroid geometries. ConclusionsDirect MultiSearch was proven as an effective tool to aid in the design of tissue engineering scaffolds. This adaptable optimization framework has potential applications beyond bone tissue engineering, including cartilage tissue differentiation.

Determination of the Optimum Architecture of Additively Manufactured Magnetic Bioactive Glass Scaffolds for Bone Tissue Engineering and Drug-Delivery Applications.

For better bone regeneration, precise control over the architecture of the scaffolds is necessary. Because the shape of the pore may affect the bone regeneration, therefore, additive manufacturing has been used in this study to fabricate magnetic bioactive glass (MBG) scaffolds with three different architectures, namely, grid, gyroid, and Schwarz D surface with 15 × 15 × 15 mm3 dimensions and 70% porosity. These scaffolds have been fabricated using an in-house-developed material-extrusion-based additive manufacturing system. The composition of bioactive glass was selected as 45% SiO2, 20% Na2O, 23% CaO, 6% P2O5, 2.5% B2O3, 1% ZnO, 2% MgO, and 0.5% CaF2 (wt %), and additionally 0.4 wt % of iron carbide nanoparticles were incorporated. Afterward, MBG powder was mixed with a 25% (w/v) Pluronic F-127 solution to prepare a slurry for fabricating scaffolds at 23% relative humidity. The morphological characterization using microcomputed tomography revealed the appropriate pore size distribution and interconnectivity of the scaffolds. The compressive strengths of the fabricated grid, gyroid, and Schwarz D scaffolds were found to be 14.01 ± 1.01, 10.78 ± 1.5, and 12.57 ± 1.2 MPa, respectively. The in vitro study was done by immersing the MBG scaffolds in simulated body fluid for 1, 3, 7, and 14 days. Darcy's law, which describes the flow through porous media, was used to evaluate the permeability of the scaffolds. Furthermore, an anticancer drug (Mitomycin C) was loaded onto these scaffolds, wherein these scaffolds depicted good release behavior. Overall, gyroid-structured scaffolds were found to be the most suitable among the three scaffolds considered in this study for bone tissue engineering and drug-delivery applications.

Design, fabrication and biocompatibility of 3D printed poly (LLA-ran-PDO-ran-GA)/poly(D-lactide) composite scaffolds for bone tissue engineering

Design, fabrication and biocompatibility of 3D printed poly (LLA-ran-PDO-ran-GA)/poly(D-lactide) composite scaffolds for bone tissue engineering

Hierarchical materials with interconnected pores from capillary suspensions for bone tissue engineering

AbstractThe increasing demand for bone grafts due to the aging population has opened new opportunities for the manufacture of porous ceramics to assist in bone reconstruction. In our study, we investigate a new, promising method to manufacture hierarchically porous structures in a straightforward and tunable way. It consists of combining the novel technology of capillary suspensions, formed by mixing solid particles and two immiscible liquids, one less than 5 vol%, with freeze casting. We have successfully achieved alumina and beta‐tricalcium phosphate (β‐TCP) materials with both <2 µm and 20–50 µm as the smallest and largest pore sizes, respectively. The microstructure exhibits fully open pores and high levels of porosity (>60%). The capillary suspensions’ rheological behavior indicates that silica nano‐suspensions as a secondary fluid creates a stronger internal particle network than sucrose for the alumina system. Conversely, the opposite was observed with the β‐TCP system. These differences were attributed to the change in affinity between the secondary fluids and the solid loading. In our study, both systems have served to deepen the knowledge about the new area of capillary suspensions and proved their use in hierarchical porous scaffolds for bone tissue engineering.

Fabrication and characterization of nanohydroxyapatite/chitosan/decellularized placenta scaffold for bone tissue engineering applications

Novel biomaterials are necessary to fabricate biomimetic scaffolds for bone tissue engineering. In the present experiment, we aimed to fabricate and evaluate the osteogenic properties of nanohydroxyapatite/chitosan/decellularized placenta (nHA.Cs.dPL) composite scaffolds. The human placenta was decellularized (dPL), characterized, and digested in pepsin to form the hydrogel. nHA.Cs.dPL scaffolds were fabricated using salt leaching/freeze drying and evaluated for their morphology, chemical composition, swelling, porosity, degradation, mechanical strength, and biocompatibility. Saos-2 cells were seeded on scaffolds, and their osteogenic properties were investigated by evaluating alkaline phosphatase (ALP), osteocalcin (OCN), collagen type 1 (COL I) expression, and calcium deposition under osteogenic differentiation. The dPL was prepared with minimized DNA content and a well-preserved porous structure. Scaffolds were highly porous with interconnected pores and exhibited appropriate swelling and degradation rates supporting saos-2 cell attachment and proliferation. dPL improved scaffold physicochemical features and increased cell proliferation, ALP, OCN, COL I expression, and calcium deposition under osteogenic differentiation induction. nHA.Cs.dPL composite scaffolds provide a 3D microenvironment with superior physicochemical features that support saos-2 cell adhesion, proliferation, and osteogenic differentiation.

Fabrication of ZnO-loaded, polycaprolactone -based, antibacterial 3D scaffolds for bone tissue engineering using melt-electrowriting

The potential of melt-electrowriting (MEW) to fabricate highly porous 3D composite scaffolds for bone tissue engineering (BTE) with antibacterial attachment properties was explored. Zinc oxide (ZnO) nanoparticles (NPs) were loaded into biodegradable medical grade Polycaprolactone (PCL) loaded with 10 wt% hydroxyapatite (HA) NPs to create antibacterial constructs by the MEW technique. The constructs’ morphology, chemical, thermal and mechanical properties, osteoblasts cell viability and bacterial attachment were investigated. Our results demonstrate a unique homogeneous dispersion of ZnO-HA NPs in the outer shell of the fabricated composite fibres by MEW, leading to significant inhibition of bacterial attachment against microorganisms. This novel composite MEW 3D scaffolds yielded promising multifunctional constructs with high potential in BTE.

Leveraging Machine Learning for Optimized Mechanical Properties and 3D Printing of PLA/cHAP for Bone Implant.

This study explores the fabrication and characterisation of 3D-printed polylactic acid (PLA) scaffolds reinforced with calcium hydroxyapatite (cHAP) for bone tissue engineering applications. By varying the cHAP content, we aimed to enhance PLA scaffolds' mechanical and thermal properties, making them suitable for load-bearing biomedical applications. The results indicate that increasing cHAP content improves the tensile and compressive strength of the scaffolds, although it also increases brittleness. Notably, incorporating cHAP at 7.5% and 10% significantly enhances thermal stability and mechanical performance, with properties comparable to or exceeding those of human cancellous bone. Furthermore, this study integrates machine learning techniques to predict the mechanical properties of these composites, employing algorithms such as XGBoost and AdaBoost. The models demonstrated high predictive accuracy, with R2 scores of 0.9173 and 0.8772 for compressive and tensile strength, respectively. These findings highlight the potential of using data-driven approaches to optimise material properties autonomously, offering significant implications for developing custom-tailored scaffolds in bone tissue engineering and regenerative medicine. The study underscores the promise of PLA/cHAP composites as viable candidates for advanced biomedical applications, particularly in creating patient-specific implants with improved mechanical and thermal characteristics.

Synthesis of N, N,O and O-carboxymethyl chitosan derivatives of controllable substitution degrees and their utilization as electrospun scaffolds for bone tissue engineering

Most chitosan (CS) carboxymethylation approaches are weighed down by insufficient description protocols regarding the reaction specificity and the degree of substitution (DS). Here, we provide three carboxymethylation protocols of enhanced specificity towards the amine (N-), amine/hydroxy (N,O-) and hydroxy (O-) groups of CS. The DS for all samples was found to be ∼70 %, as confirmed by NMR analysis. To illustrate the modified materials' potential in bone tissue regeneration, each derivative was blended with poly(vinyl alcohol) to prepare scaffolds via electrospinning. Both materials and electrospun membranes were characterized in terms of their physicochemical properties by Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry and water contact angle measurements. The electrospun membranes' swelling ratio, degradation, tensile strength, as well as morphology were also examined through scanning electron microscopy before and after heat treatment at 120 °C, which was used as a method of physical stabilization, leading to significantly enhanced degradation rate and mechanical strength. The three electrospun scaffold types were loaded with MC3T3-E1 pre-osteoblastic cells and their cell adhesion, viability and growth rate were assessed. Finally, osteogenic differentiation was examined by means of alkaline phosphatase activity measurement, calcium mineralization and formation of extracellular matrix markers, with all materials showing promising prospects.

Bone Tissue Engineering Scaffold Film with Controlled Release of Tea Polyphenol-Magnesium Nanoformulations to Prevent Bacterial Infection

Bone Tissue Engineering Scaffold Film with Controlled Release of Tea Polyphenol-Magnesium Nanoformulations to Prevent Bacterial Infection

Hybrid scaffolds for bone tissue engineering: Integration of composites and bioactive hydrogels loaded with hDPSCs

Bone tissue regeneration remains a significant challenge in clinical settings due to the complexity of replicating the mechanical and biological properties of bone environment. This study addresses this challenge by proposing a hybrid scaffold designed to enhance both bioactivity and physical stability for bone tissue regeneration. This research is the fisrt to develop a rigid 3D structure composed of polycaprolactone (PCL) and hydroxyapatite nanoparticles (nHA) integrated with a bioink containing human dental pulp stem/stromal cells (hDPSCs), alginate, nHA and collagen (Col). The biofabricated constructs were extensively characterized through cytocompatibility tests, osteogenic differentiation assessment, and biocompatibility evaluation in a rat model. In vitro results demontrated that the hybrid scaffolds presented significantly higher cell viability after 168 h compared to the control group. Furthermore, the hybrid scaffolds showed increased osteogenic differentiation relative to other groups. In vivo evaluation indicated good biocompatibility, characterized by minimal inflammatory response and successful tissue integration. These findings highlight the scaffold's potential to support bone tissue regeneration by combining the mechanical strength of PCL and nHA with the biological activity of the alginate-nHA-Col and hDPSCs bioink. The current study provides a promising foundation for the development of biomaterials aimed at improving clinical outcomes in bone repair and regeneration, particulary for the treatment of critical-size bone defects, targeted drug administration, and three-dimensional models for bone tissue engineering.

Osteogenic potentials in canine mesenchymal stem cells: unraveling the efficacy of polycaprolactone/hydroxyapatite scaffolds in veterinary bone regeneration

BackgroundThe integration of stem cells, signaling molecules, and biomaterial scaffolds is fundamental for the successful engineering of functional bone tissue. Currently, the development of composite scaffolds has emerged as an attractive approach to meet the criteria of ideal scaffolds utilized in bone tissue engineering (BTE) for facilitating bone regeneration in bone defects. Recently, the incorporation of polycaprolactone (PCL) with hydroxyapatite (HA) has been developed as one of the suitable substitutes for BTE applications owing to their promising osteogenic properties. In this study, a three-dimensional (3D) scaffold composed of PCL integrated with HA (PCL/HA) was prepared and assessed for its ability to support osteogenesis in vitro. Furthermore, this scaffold was evaluated explicitly for its efficacy in promoting the proliferation and osteogenic differentiation of canine bone marrow-derived mesenchymal stem cells (cBM-MSCs) to fill the knowledge gap regarding the use of composite scaffolds for BTE in the veterinary orthopedics field.ResultsOur findings indicate that the PCL/HA scaffolds substantially supported the proliferation of cBM-MSCs. Notably, the group subjected to osteogenic induction exhibited a markedly upregulated expression of the osteogenic gene osterix (OSX) compared to the control group. Additionally, the construction of 3D scaffold constructs with differentiated cells and an extracellular matrix (ECM) was successfully imaged using scanning electron microscopy. Elemental analysis using a scanning electron microscope coupled with energy-dispersive X-ray spectroscopy confirmed that these constructs possessed the mineral content of bone-like compositions, particularly the presence of calcium and phosphorus.ConclusionsThis research highlights the synergistic potential of PCL/HA scaffolds in concert with cBM-MSCs, presenting a multidisciplinary approach to scaffold fabrication that effectively regulates cell proliferation and osteogenic differentiation. Future in vivo studies focusing on the repair and regeneration of bone defects are warranted to further explore the regenerative capacity of these constructs, with the ultimate goal of assessing their potential in veterinary clinical applications.

Bone Tissue Engineering with Adipose-Derived Stem Cells in Polycaprolactone/Graphene Oxide/Dexamethasone 3D-Printed Scaffolds.

We fabricated three-dimensional (3D)-printed polycaprolactone (PCL) and PCL/graphene oxide (GO) (PGO) scaffolds for bone tissue engineering. An anti-inflammatory and pro-osteogenesis drug dexamethasone (DEX) was adsorbed onto GO and a 3D-printed PGO/DEX (PGOD) scaffold successfully improved drug delivery with a sustained release of DEX from the scaffold up to 1 month. The physicochemical properties of the PCL, PGO, and PGOD scaffolds were characterized by various analytical techniques. The biological response of these scaffolds was studied for adherence, proliferation, and osteogenic differentiation of seeded rabbit adipose-derived stem cells (ASCs) from DNA assays, alkaline phosphatase (ALP) production, calcium quantification, osteogenic gene expression, and immunofluorescence staining of osteogenic marker proteins. The PGOD scaffold was demonstrated to be the best scaffold for maintaining cell viability, cell proliferation, and osteogenic differentiation of ASCs in vitro. In vivo biocompatibility of PGOD was confirmed from subcutaneous implantation in nude mice where ASC-seeded PGOD can form ectopic bones, demonstrated by microcomputed tomography (micro-CT) analysis and immunofluorescence staining. Furthermore, implantation of PGOD/ASCs constructs into critical-sized cranial bone defects in rabbits form tissue-engineered bones at the defect site, observed using micro-CT and histological analysis.

Composite bioink incorporating cell-laden liver decellularized extracellular matrix for bioprinting of scaffolds for bone tissue engineering

The field of bone tissue engineering (BTE) has witnessed a revolutionary breakthrough with the advent of three-dimensional (3D) bioprinting technology, which is considered an ideal choice for constructing scaffolds for bone regeneration. The key to realizing scaffold biofunctions is the selection and design of an appropriate bioink, and existing bioinks have significant limitations. In this study, a composite bioink based on natural polymers (gelatin and alginate) and liver decellularized extracellular matrix (LdECM) was developed and used to fabricate scaffolds for BTE using 3D bioprinting. Through in vitro studies, the concentration of LdECM incorporated into the bioink was optimized to achieve printability and stability and to improve the proliferation and osteogenic differentiation of loaded rat bone mesenchymal stem cells (rBMSCs). Furthermore, in vivo experiments were conducted using a Sprague Dawley rat model of critical-sized calvarial defects. The proposed rBMSC-laden LdECM–gelatin–alginate scaffold, bioprinted layer-by-layer, was implanted in the rat calvarial defect and the development of new bone growth was studied for four weeks. The findings showed that the proposed bioactive scaffolds facilitated angiogenesis and osteogenesis at the defect site. The findings of this study suggest that the developed rBMSC-laden LdECM–gelatin–alginate bioink has great potential for clinical translation and application in solving bone regeneration problems.

Phloridzin functionalized gelatin-based scaffold for bone tissue engineering

Polyphenol-functionalized biomaterials are significant in the field of bone tissue engineering (BTE) due to their antioxidant, anti-inflammatory, and osteoinductive properties. In this study, a gelatin (Gel)-based scaffold was functionalized with phloridzin (Ph), the primary polyphenol in apple by-products, to investigate its influence on physicochemical and morphological, properties of the scaffold for BTE application. A preliminary assessment of the biological properties of the functionalized scaffold was also undertaken. The Ph-functionalized scaffold (Gel/Ph) exhibited a porous structure with high porosity (71.3 ± 0.3 %), a pore size of 206.5 ± 1.7 μm, and a radical scavenging activity exceeding 70 %. This scaffold with Young's modulus of 10.8 MPa was determined to support cell proliferation and exhibited cytocompatibility with mesenchymal stem cells (MSCs). Incorporating hydroxyapatite nanoparticle (HA) in the Gel/Ph scaffold stimulated the osteogenic differentiation of key osteogenic genes, including Runx2, ALPL, COL1A1, and OSX ultimately promoting mineralization. This research highlights the promising potential of utilizing polyphenolic compounds derived from fruit waste to functionalize scaffolds for BTE applications.