Design Of Scaffolds Research Articles

Rational design of 3D-printed scaffolds for breast tissue engineering using structural analysis.

Best cosmetic outcomes of breast reconstruction using tissue engineering techniques rely on the scaffold architecture and material, which are currently both to be determined. This study suggests an approach for a rational design of breast-shaped scaffold architecture, in which structural analysis is implemented to predict its stiffness and adjust it to that of the native tissue. This approach can help achieve the goal of optimal scaffold architecture for breast tissue engineering. 
Based on specifications defined in a preliminary implantation study of a non-rationally designed scaffold, and using analytical modeling and finite element analysis (FEA), we rationally designed a polycaprolactone (PCL) made, 3D-printed, highly porous, breast-shaped scaffold with a stiffness similar to the breast adipose tissue. This scaffold had an architecture of a double-shelled dome connected by pillars, with no bottom to allow direct contact of its fat graft with the host's blood vessels (Shelled Hemisphere Adaptive Design (SHAD)). To demonstrate the potential of the SHAD scaffold in breast tissue engineering, a proof-of-concept study was performed, in which SHAD scaffolds were embedded with human adipose derived mesenchymal stem cells (hAdMSCs), isolated from lipoaspirates, and implanted in Nod-Scid-Gamma (NSG) mouse model with a delayed fat graft injection. After 4 weeks of implantation, the SHAD implants were vascularized with a viable fat graft, indicating the suitability of the SHAD scaffold for breast tissue engineering. 
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Geometric stability and optimization in reaction–diffusion models for tissue engineering: A case study with hydrogel scaffolds

This paper presents a thorough qualitative analysis of coupled reaction–diffusion equations, with an emphasis on the careful selection of boundary conditions that govern the interactions between stem cell and nanozyme concentrations within hydrogel scaffolds. These scaffolds, widely applied in cartilage tissue repair, possess unique attributes such as tunable mechanical strength and high water content, which are captured within the model through carefully chosen parametric constraints. The precision in defining boundary conditions is particularly crucial, as stem cell proliferation within these scaffolds is highly sensitive to external parameters, directly influencing their behavior. Our approach employs a geometric framework to analyze the stability of the coupled system, with a focus on discerning the delicate balance between stem cell populations and nanozyme concentrations. The goal is to ensure that the scaffold sustains optimal mechanical integrity, achieves uniform cell distribution, and maintains controlled degradation rates. Through a rigorous stability and bifurcation analysis of the reaction–diffusion equations, we explore the system’s equilibrium points and establish conditions under which these equilibria are stable or unstable. This analysis serves as a theoretical foundation for optimizing the design of hydrogel scaffolds, particularly in the context of ensuring consistent mechanical properties and efficient cellular integration. In addition to the qualitative geometric methods, we integrate Optuna, an advanced optimization algorithm, to fine-tune the model parameters. This computational tool enhances the accuracy of the parameter selection process by efficiently navigating the solution space, thereby refining the predictions of scaffold performance. The combination of geometric stability analysis with the state-of-the-art optimization provides a novel framework for addressing challenges in tissue engineering, offering new insights into the dynamics of scaffold design and the development of experimental protocols. These findings not only elucidate the stability conditions of the system but also contribute in establishing rigorous guidelines for the control of stem cell populations and nanozyme delivery rates in practical applications.

Salt-Compact Albumin as a New Pure Protein-based Biomaterials: From Design to In Vivo Studies.

Current biodegradable materials are facing many challenges when used for the design of implantable devices because of shortcomings such as toxicity of crosslinking agents and degradation derivatives, limited cell adhesion, and limited immunological compatibility. Here, a class of materials built entirely of stable protein is designed using a simple protocol based on salt-assisted compaction of albumin, breaking with current crosslinking strategies. Salt-assisted compaction is based on the assembly of albumin in the presence of high concentrations of specific salts such as sodium bromide. This process leads, surprisingly, to water-insoluble handable materials with high preservation of their native protein structures and Young's modulus close to that of cartilage (0.86MPa). Furthermore, these materials are non-cytotoxic, non-inflammatory, and in vivo implantations (using models of mice and rabbits) demonstrate a very slow degradation rate of the material with excellent biocompatibility and absence of systemic inflammation and implant failure. Therefore, these materials constitute promising candidates for the design of biodegradable scaffolds and drug delivery systems as an alternative to conventional synthetic degradable polyester materials.

Enhancing Osteogenesis and Mechanical Properties through Scaffold Design in 3D Printed Bone Substitutes.

In the context of regenerative medicine, the design of scaffolds to possess excellent osteogenesis and appropriate mechanical properties has gained significant attention in bone tissue engineering. In this review, we categorized materials into metallic, inorganic, nonmetallic, organic polymer, and composite materials. This review provides a more integrated and multidimensional analysis of scaffold design for bone tissue engineering. Unlike previous works that often focus on single aspects, such as material type or fabrication technique, our review takes a broader approach. It analyzes the interaction between scaffold materials, 3D printing techniques, scaffold structural designs, modification methods, porosities, and pore sizes, and the composition of materials (particularly composite materials). Meanwhile, it focuses on their impacts on scaffolds' osteogenic potential and mechanical performance. This review also provides suggested ranges for porosity and pore size for different materials and outlines recommended surface modification methods. This approach not only consolidates current knowledge but also highlights the interdependencies among various factors affecting scaffold efficacy, offering deeper insights into optimization strategies tailored for specific clinical conditions. Furthermore, we introduce recent advancements in innovative 3D printing techniques and novel composite materials, which are rarely addressed in previous reviews, thereby providing a forward-looking perspective that informs future research directions and clinical applications.

Biodegradable Stents in the Treatment of Arterial Stenosis.

Arterial diseases (ADs) are a significant health problem, with high mortality and morbidity rates. Endovascular interventions, such as balloon angioplasty (BA), bare-metal stents (BMSs), drug-eluting stents (DESs) and drug-coated balloons (DCBs), have made significant progress in their treatments. However, the issue has not been fully resolved, with restenosis remaining a major concern. In this context, bioresorbable vascular stents (BVSs) have emerged as a promising area of investigation. This manuscript includes articles that assess the use of BVSs. Studies have identified ongoing challenges, such as negative vascular remodeling and elastic recoil post-angioplasty, stent-related injury, and in-stent restenosis following BMS placement. While DESs have mitigated these issues to a considerable extent, their durable structures are unable to prevent late stent thrombosis and delay arterial recovery. BVSs, with their lower support strength and tendency towards thicker scaffolds, increase the risk of scaffold thrombosis. Despite inconsistent study results, the superiority of BVSs over DESs has not been demonstrated in randomized trials, and DES devices continue to be the preferred choice for most cases of arterial disease. Esprit BTK (Abbott Vascular) received approval from the US FDA for below-knee lesions in 2024, offering hope for the use of BVSs in other vascular conditions. Enhancing the design and thickness of BVS scaffolds may open up new possibilities. Large-scale and longer-term comparative studies are still required. This article aims to provide an overview of the use of biodegradable stents in the endovascular treatment of vascular stenosis.

Research progress of bioactive scaffolds in repair and regeneration of osteoporotic bone defects

To summarize the research progress of bioactive scaffolds in the repair and regeneration of osteoporotic bone defects. Recent literature on bioactive scaffolds for the repair of osteoporotic bone defects was reviewed to summarize various types of bioactive scaffolds and their associated repair methods. The application of bioactive scaffolds provides a new idea for the repair and regeneration of osteoporotic bone defects. For example, calcium phosphate ceramics scaffolds, hydrogel scaffolds, three-dimensional (3D)-printed biological scaffolds, metal scaffolds, as well as polymer material scaffolds and bone organoids, have all demonstrated good bone repair-promoting effects. However, in the pathological bone microenvironment of osteoporosis, the function of single-material scaffolds to promote bone regeneration is insufficient. Therefore, the design of bioactive scaffolds must consider multiple factors, including material biocompatibility, mechanical properties, bioactivity, bone conductivity, and osteogenic induction. Furthermore, physical and chemical surface modifications, along with advanced biotechnological approaches, can help to improve the osteogenic microenvironment and promote the differentiation of bone cells. With advancements in technology, the synergistic application of 3D bioprinting, bone organoids technologies, and advanced biotechnologies holds promise for providing more efficient bioactive scaffolds for the repair and regeneration of osteoporotic bone defects.

Establishing a framework for the design and fabrication of patient-specific scaffolds targeting partial meniscal defects

Meniscal injuries are a leading cause of knee dysfunction and are commonly treated with partial meniscectomy, which often leads to altered joint biomechanics and early-onset osteoarthritis. Current meniscal implants and scaffolds fail to address patient-specific anatomical variations, particularly for partial defects, limiting their clinical effectiveness. This pioneering study introduces the first methodology specifically designed to develop patient-specific scaffolds tailored to partial meniscal injuries, representing a groundbreaking advancement in the field. Using medical imaging and computer-aided design, precise 3D models of injured and intact menisci were created, leveraging the contralateral meniscus as a reference. Scaffolds were fabricated through extrusion-based 3D printing, enabling accurate replication of the defect geometry. Ex vivo analyses demonstrated the scaffolds’ adaptability to diverse defect types and their morphological fidelity to the native tissue. Quantitative assessments revealed minimal deviations, underscoring the precision of the proposed method. This innovative methodology provides a robust framework for developing anatomically precise scaffolds, paving the way for personalized regenerative strategies. Beyond its current application, it holds potential for creating cell-laden scaffolds, acellular implants, or permanent prosthetic devices, addressing critical challenges in meniscal repair and advancing patient-specific tissue engineering.

WITHDRAWN: Design and Synthesis of Novel Phthalazine Scaffolds Linked to 1,3,4-oxadiazolyl-1,2,3-triazoles as Potent Anticancer Agents: A Computational Docking Analysis

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Polycaprolactone for Hard Tissue Regeneration: Scaffold Design and In Vivo Implications.

In the last thirty years, tissue engineering (TI) has emerged as an alternative method to regenerate tissues and organs and restore their function by implanting specific lineage cells, growth factors, or biomolecules functionalizing a matrix scaffold. Recently, several pathologies have led to bone loss or damage, such as malformations, bone resorption associated with benign or malignant tumors, periodontal disease, traumas, and others in which a discontinuity in tissue integrity is observed. Bone tissue is characterized by different stiffness, mechanical traction, and compression resistance as a function of the different compartments, which can influence susceptibility to injury or destruction. For this reason, research into repairing bone defects began several years ago to find a scaffold to improve bone regeneration. Different techniques can be used to manufacture 3D scaffolds for bone tissue regeneration based on optimizing reproducible scaffolds with a controlled hierarchical porous structure like the extracellular matrix of bone. Additionally, the scaffolds synthesized can facilitate the inclusion of bone or mesenchymal stem cells with growth factors that improve bone osteogenesis, recruiting new cells for the neighborhood to generate an optimal environment for tissue regeneration. In this review, current state-of-the-art scaffold manufacturing based on the use of polycaprolactone (PCL) as a biomaterial for bone tissue regeneration will be described by reporting relevant studies focusing on processing techniques, from traditional-i.e., freeze casting, thermally induced phase separation, gas foaming, solvent casting, and particle leaching-to more recent approaches, such as 3D additive manufacturing (i.e., 3D printing/bioprinting, electrofluid dynamics/electrospinning), as well as integrated techniques. As a function of the used technique, this work aims to offer a comprehensive overview of the benefits/limitations of PCL-based scaffolds in order to establish a relationship between scaffold composition, namely integration of other biomaterial phases' structural properties (i.e., pore morphology and mechanical properties) and in vivo response.

Pioneering a New Era in Oral Cancer Treatment with Electrospun Nanofibers: A Comprehensive Insight.

Oral cancer, currently ranked 16th among the most prevalent malignancies worldwide according to GLOBOCAN, presents significant challenges to global oral health. Conventional treatment modalities such as surgery, radiation, and chemotherapy often have limitations, prompting the need for innovative therapeutic approaches. Tissue engineering has emerged as a promising solution aimed at developing biocompatible, functional, and biologically responsive tissue constructs. This approach involves the integration of cells, bioactive compounds, and scaffolds to enhance treatment efficacy. Electrospun nanofibers, mimicking the extracellular matrix, exhibit considerable potential in addressing complex oral health issues by influencing cellular behavior. The versatility of electrospinning technology allows for the fabrication of fiber scaffolds with high surface area, making them ideal for localized delivery of bioactive compounds or pharmaceuticals. Enhancing these electrospun scaffolds with growth factors, nanoparticles, and biologically active substances significantly increases their therapeutic appeal in oral cancer management. This review offers a comprehensive examination of the various applications of electrospun nanofibers in oral cancer therapy. Utilizing electronic databases such as PubMed, CrossREF, and Google Scholar, we conducted an extensive review of relevant literature concerning "electrospun nanofibers" and their therapeutic potential in oral cancer treatment. Key topics addressed include engineering methodologies, drug diffusion mechanisms, factors influencing nanofiber scaffold design, toxicity concerns, and clinical implications. The findings underscore the transformative potential of electrospun nanofibers in revolutionizing oral cancer therapy.

Osteogenic differentiation of mesenchymal stem cell on poly sorbitol sebacate scaffold under shear stress in a bioreactor.

Mechanical loading plays a pivotal role in regulating bone anabolic processes. Understanding the optimal mechanical loading parameters for cellular responses is critical for advancing strategies in orthopedic bioreactor-based bone tissue engineering. This study developed a poly (sorbitol sebacate) (PSS) filmscaffold with a sorbitol-to-sebacic acid molar ratio of 1:4. The scaffold underwent extensive characterization, including physical and mechanical property evaluations, biocompatibility assessments, and cell adhesion analysis. The Young's modulus of the PSS polymer was determined to be 6.81 ± 0.44 MPa under dry conditions, 6.37 ± 1.09 MPa in a wet state, and 6.38 ± 0.71 MPa after ethanol washing (70 %). The average contact angle of the PSS film was measured at 88.806 ± 1.644°, indicating moderate hydrophilicity. To investigate the osteogenic potential, a fluid flow inducing a shear stress of 1 Pa at a frequency of 1 Hz was applied to mesenchymal stem cells (MSCs) cultured on the PSS scaffold. Cells were exposed to dynamic fluid flow for one hour daily on days 4, 5, 6, and 7 of culture, followed by a static culture period of 14 days. The expression of osteogenic differentiation markers, including osteopontin (OPN), osteocalcin (OCN), type I collagen, and calcium deposition, was significantly elevated under dynamic conditions compared to static culture. This study highlights the importance of mechanical stimulation in enhancing MSC osteogenesis and underscores the osteoconductive properties of the PSS scaffold. These findings provide valuable insights into scaffold design and mechanical loading strategies for laboratory-based bone tissue engineering applications.

Osteochondral Tissue Engineering: Scaffold Materials, Fabrication Techniques and Applications.

Osteochondral damage, caused by trauma, tumors, or degenerative diseases, presents a major challenge due to the limited self-repair capacity of the tissue. Traditional treatments often result in significant trauma and unpredictable outcomes. Recent advances in bone/cartilage tissue engineering, particularly in scaffold materials and fabrication technologies, offer promising solutions for osteochondral regeneration. This review highlights the selection and design of scaffolds using natural and synthetic materials such as collagen, chitosan (Cs), and polylactic acid (PLA), alongside inorganic components like bioactive glass and nano-hydroxyapatite (nHAp). Key fabrication techniques-freeze-drying, electrospinning, and 3D printing-have improved scaffold porosity and mechanical properties. Special focus is placed on the design of multiphasic scaffolds that mimic natural tissue structures, promoting cell adhesion and differentiation and supporting the regeneration of cartilage and subchondral bone. In addition, the current obstacles and future directions for regenerating damaged osteochondral tissues will be discussed.

Melt Electrowriting for Biomimetic Tissue Engineering: Advances in Scaffold Design, Materials, and Multifunctional Applications

Melt Electrowriting for Biomimetic Tissue Engineering: Advances in Scaffold Design, Materials, and Multifunctional Applications

Controllable design and evaluation of Voronoi-based irregular porous scaffolds for bone restoration

The Voronoi-based irregular porous scaffolds (VIPS) for bone restoration often suffer from uncontrollable structural characteristics and mechanical properties. In this study, a method using spherical spaces to control the randomness of the seed points distribution was proposed to achieve controllable design of the VIPS. The irregularity ε, porosity P and average pore size D̅ of the VIPS were calculated by parametric design software Grasshopper, and the apparent elastic modulus E, equivalent compressive strength S of the VIPS were obtained by quasi-static compressive test. The functional relationships between the design parameters (spherical radius to lattice spacing ratio R/a, seed points number N and pore size coefficient K) and ε, P, D̅, E, S were established through statistical analyses. The results indicated that the VIPS designed based on the spherical space method had high controllability. Design parameters in the range of R/a∈0,0.5, N∈64,1000, and K∈0.4,0.9 allow control over the irregularity, porosity, average pore size, elastic modulus, and compressive strength of VIPS in the range of 0–0.32, 37%–96%, 200–1200 μm, 0.8–5.4GPa, 15–240MPa, respectively, and all of which could meet the structural and mechanical requirements of the VIPS for bone restoration.

Predicting inflammatory response of biomimetic nanofibre scaffolds for tissue regeneration using machine learning and graph theory.

Tissue regeneration after a wound occurs through three main overlapping and interrelated stages namely inflammatory, proliferative, and remodelling phases, respectively. The inflammatory phase is key for successful tissue reconstruction and triggers the proliferative phase. The macrophages in the non-healing wounds remain in the inflammatory loop, but their phenotypes can be changed via interactions with nanofibre-based scaffolds mimicking the organisation of the native structural support of healthy tissues. However, the organisation of extracellular matrix (ECM) is highly complex, combining order and disorder, which makes it difficult to replicate. The possibility of predicting the desirable biomimetic geometry and chemistry of these nanofibre scaffolds would streamline the scaffold design process. Fifteen families of nanofibre scaffolds, electrospun from combinations of polyesters (polylactide, polyhydroxybutyrate), polysaccharides (polysucrose, carrageenan, cellulose), and polyester ether (polydioxanone) were investigated and analysed using machine learning (ML). The Random Forest model had the best performance (92.8%) in predicting inflammatory responses of macrophages on the nanoscaffolds using tumour necrosis factor-alpha as the output. CellProfiler proved to be an effective tool to process scanning electron microscopy (SEM) images of the macrophages on the scaffolds, successfully extracting various features and measurements related to cell phenotypes M0, M1, and M2. Deep learning modelling indicated that convolutional neural network models have the potential to be applied to SEM images to classify macrophage cells according to their phenotypes. The complex organisation of the nanofibre scaffolds can be analysed using graph theory (GT), revealing the underlying connectivity patterns of the nanofibres. Analysis of GT descriptors showed that the electrospun membranes closely mimic the connectivity patterns of the ECM. We conclude that ML-facilitated, GT-quantified engineering of cellular scaffolds has the potential to predict cell interactions, streamlining the pipeline for tissue engineering.

Additively manufactured stochastic and gyroid scaffold design towards osseointegration and bone regeneration in a rabbit femur model

Additively manufactured stochastic and gyroid scaffold design towards osseointegration and bone regeneration in a rabbit femur model

Fabrication of a micropatterned shape-memory polymer patch with L-DOPA for tendon regeneration.

A scaffold design for tendon regeneration has been proposed, which mimics the microstructural features of tendons and provides appropriate mechanical properties. We synthesized a temperature-triggered shape-memory polymer (SMP) using the ring-opening polymerization of polycaprolactone (PCL) with polyethylene glycol (PEG) as a macroinitiator. We fabricated a micropatterned patch using SMP via capillary force lithography, which mimicked a native tendon, for providing physical cues and guiding effects. The SMP patches (the SMP-flat patch is referred to as SMP-F, and the SMP-patterned patch is referred to as SMP-P) were surface-modified with 3,4-dihydroxy-L-phenylalanine (L-DOPA, referred to as D) for improving cell adhesion. We hypothesized that SMP patches could be applied in minimally invasive surgery and the micropatterned structure would improve tendon regeneration by providing geometrical cues. The SMP patches exhibited excellent shape-memory properties, mechanical performance, and biocompatibility in vitro and in vivo. Especially, SMP-DP demonstrated enhanced cell behaviors in vitro, including cell orientation, elongation, migration, and tenogenic differentiation potential. The in vivo data showed notable biomechanical functionality and histological morphometric findings in various analyses of SMP-DP in the ruptured Achilles tendon model.

Study on the mechanical properties of Ti-6Al-4V alloy with minimal surface structures: effects of different heat treatment temperatures

Abstract Triply periodic minimal surface (TPMS) structures are widely used in scaffold design for biomaterials due to their excellent porous architecture and mechanical properties. This study utilized selective laser melting (SLM) to fabricate TPMS scaffold models with porosities of 50%, 60%, 70%, and 80%, based on Gyroid and Primitive unit cells. Compression tests were conducted to investigate the changes in mechanical properties of TPMS scaffolds before and after heat treatment. The mechanisms underlying these changes were elucidated through fracture morphology analysis, microstructural observation, and finite element simulation. Results indicate that Gyroid porous scaffolds exhibit superior compressive performance compared to Primitive scaffolds, with yield strength inversely related to porosity—lower porosity corresponds to higher yield strength. During compression, Primitive scaffolds exhibited a layer-by-layer stacking failure mode, whereas Gyroid scaffolds displayed a 45° shear failure mode. The Gyroid porous scaffolds showed uniform and continuous stress distribution, and heat treatment effectively relieved residual stresses, enhancing yield strength and toughness. In contrast, Primitive porous scaffolds demonstrated stress concentration regions that reach yield limits under compression, leading to fracture. Heat treatment did not alleviate these stress concentrations but instead reduced the material’s yield limit, accelerating scaffold failure.

Comparative evaluation of melt- vs. solution-printed poly(ε-caprolactone)/hydroxyapatite scaffolds for bone tissue engineering applications.

Material extrusion-based three-dimensional (3D) printing is a widely used manufacturing technology for fabricating scaffolds and devices in bone tissue engineering (BTE). This technique involves two fundamentally different extrusion approaches: solution-based and melt-based printing. In solution-based printing, a polymer solution is extruded and solidifies via solvent evaporation, whereas in melt-based printing, the polymer is melted at elevated temperatures and solidifies as it cools post-extrusion. Solution-based printing can also be enhanced to generate micro/nano-scale porosity through phase separation by printing the solution into a nonsolvent bath. The choice of the printing method directly affects scaffold properties and the biological response of stem cells. In this study, we selected polycaprolactone (PCL), a biodegradable polymer frequently used in BTE, blended with hydroxyapatite (HA) nanoparticles, a bioceramic known for promoting bone formation, to investigate the effects of the printing approach on scaffold properties and performance in vitro using human mesenchymal stem cells (hMSCs). Our results showed that while both printing methods produced scaffolds with similar strut and overall scaffold dimensions, solvent-based printing resulted in porous struts, higher surface roughness, lower stiffness, and increased crystallinity compared to melt-based printing. Although stem cell viability and proliferation were not significantly influenced by the printing approach, melt-printed scaffolds promoted a more spread morphology and exhibited pronounced vinculin staining. Furthermore, composite scaffolds outperformed their neat counterparts, with melt-printed composite scaffolds significantly enhancing bone formation. This study highlights the critical role of the printing process in determining scaffold properties and performance, providing valuable insights for optimizing scaffold design in BTE.

Biomedical Application of Bovine Type I Collagen and Its Fabricated Scaffolds: A Review

The transformation of waste into wealth remains a challenging yet essential endeavor, offering opportunities for efficient solid waste management. Type I collagen, abundant in bovine tendons, serves as a valuable feedstock for the extraction of this biomaterial. Derived from slaughterhouse solid waste, bovine type I collagen acts as a foundational biomaterial for tissue engineering and regenerative medicine. This fibrous protein-based eco-material features customizable properties, including biodegradability, mechanical resilience, and surface modifiability, making it a promising alternative to synthetic and biodegradable polymers. The design and development of bioactive scaffolds remain a significant challenge in regenerative medicine, tissue engineering, and drug delivery. Collagen-based biomaterial scaffolds, which mimic the extracellular matrix, are extensively utilized as templates for tissue regeneration in biomedical applications. These scaffolds enhance wound healing and facilitate the maturation of collagen fibers, promoting the rapid formation of mature, aligned tissue at wound sites. This review provides a comprehensive analysis of the biomedical applications of collagen-based biomaterials, including their isolation and purification from bovine tendons, characterization, scaffold fabrication, ciprofloxacin/Triphala conjugation into scaffolds, biochemical and histological wound healing investigations, drug delivery, and cell culture applications. Recent advancements in chemically modified collagen and collagen-biodegradable polymer composites with controlled drug delivery for wound treatment, as well as collagen-based diffusion membranes for prolonged drug release, are also discussed.