Tissue Scaffolds Research Articles

Nano hydroxyapatite architectonics to control the morphological, mechanical, and rheological properties of CH-rfGO-HA scaffolds for bone tissue

Nano hydroxyapatite architectonics to control the morphological, mechanical, and rheological properties of CH-rfGO-HA scaffolds for bone tissue

Towards Stem Cell Therapy for Critical-Sized Segmental Bone Defects: Current Trends and Challenges on the Path to Clinical Translation.

The management and reconstruction of critical-sized segmental bone defects remain a major clinical challenge for orthopaedic clinicians and surgeons. In particular, regenerative medicine approaches that involve incorporating stem cells within tissue engineering scaffolds have great promise for fracture management. This narrative review focuses on the primary components of bone tissue engineering-stem cells, scaffolds, the microenvironment, and vascularisation-addressing current advances and translational and regulatory challenges in the current landscape of stem cell therapy for critical-sized bone defects. To comprehensively explore this research area and offer insights for future treatment options in orthopaedic surgery, we have examined the latest developments and advancements in bone tissue engineering, focusing on those of clinical relevance in recent years. Finally, we present a forward-looking perspective on using stem cells in bone tissue engineering for critical-sized segmental bone defects.

From Collagen Mimetics to Collagen Hybridization and Back.

ConspectusFacilitated by the unique triple-helical protein structure, fibrous collagens, the principal proteins in animals, demonstrate a dual function of serving as building blocks for tissue scaffolds and as a bioactive material capable of swift renewal in response to environmental changes. While studies of triple-helical collagen mimetic peptides (CMPs) have been instrumental in understanding the molecular forces responsible for the folding and assembly of triple helices, as well as identifying bioactive regions of fibrous collagen molecules, single-strand CMPs that can specifically target and hybridize to denatured collagens (i.e., collagen hybridizing peptides, CHPs) have proven useful in identifying the remodeling activity of collagen-rich tissues related to development, homeostasis, and pathology. Efforts to improve the utility of CHPs have resulted in the development of new skeletal structures, such as dimeric and cyclic CHPs, as well as the incorporation of artificial amino acids, including fluorinated proline and N-substituted glycines (peptoid residues). In particular, dimeric CHPs were used to capture collagen fragments from biological fluid for biomarker study, and the introduction of peptoid-based collagen mimetics has sparked renewed interest in peptidomimetic research because peptoids enable a stable triple-helical structure and the presentation of an extensive array of side chain structures offering a versatile platform for the development of new collagen mimetics.This Account will cover the evolution of our research from CMPs as biomaterials to ongoing efforts in developing triple-helical peptides with practical theranostic potential in targeting denatured and damaged collagens. Our early efforts in functionalizing natural collagen scaffolds via noncovalent modifications led to the discovery of an entirely new use of CMPs. This discovery resulted in the development of CHPs that are now used by many different laboratories for the investigation of pathologies associated with changes in the structures of extracellular matrices including fibrosis, cancer, and mechanical damage to collagen-rich, load-bearing tissues. Here, we delve into the essential design features of CHPs contributing to their collagen binding properties and practical usage and explore the necessity for further mechanistic understanding of not only the binding processes (e.g., binding domain and stoichiometry of the hybridized complex) but also the biology of collagen degradation, from proteolytic digestion of fibrils to cellular processing of collagen fragments. We also discuss the strengths and weaknesses of peptoid-based triple-helical peptides as applied to collagen hybridization touching on thermodynamic and kinetic aspects of triple-helical folding. Finally, we highlight current limitations and future directions in the use of peptoid building blocks to develop bioactive collagen mimetics as new functional biomaterials.

Mechanically suitable and osteoinductive 3D-printed composite scaffolds with hydroxyapatite nanoparticles having diverse morphologies for bone tissue engineering.

The challenge of integrating hydroxyapatite nanoparticles (nHAp) with polymers is hindered by the conflict between the hydrophilic and hygroscopic properties of nHAp and the hydrophobic properties of polymers. This conflict particularly affects the materials when calcium phosphates, including nHAp, are used as a filler in composites in thermal processing applications such as 3D printing with fused filament fabrication (FFF). To overcome this, we propose a one-step surface modification of nHAp with calcium stearate monolayer. Moreover, to build the scaffold with suitable mechanical strength, we tested the addition of nHAp with diverse morphology-spherical, plate- and rod-like nanoparticles. Our analysis showed that the composite of polycaprolactone (PCL) reinforced with nHAp with rod and plate morphologies modified with calcium stearate monolayer exhibited a significant increase in compressive strength. However, composites with spherical nHAp added to PCL showed a significant reduction in compressive modulus and compressive strength, but both parameters were within the applicability range of hard tissue scaffolds. None of the tested composite scaffolds showed cytotoxicity in L929 murine fibroblasts or MG-63 human osteoblast-like cells, supporting the proliferation of the latter. Additionally, PCL/nHAp scaffolds reinforced with spherical nHAp caused osteoactivation of bone marrow human mesenchymal stem cells, as indicated by alkaline phosphatase activity and COL1, RUNX2, and BGLAP expression. These results suggest that the calcium stearate monolayer on the surface of the nHAp particles allows the production of polymer/nHAp composites suitable for hard tissue engineering and personalized implant production in 3D printing using the FFF technique.

Impedance spectra of soft ionics

Impedance spectroscopy is widely adopted for probing the charge and charge mobility of soft ion-conducting media, such as synthetic membranes and biological tissue. The spectra exhibit a variety of distinctive signatures, but the physical basis of these is not well understood, e.g. models have not previously accounted for viscoelasticity, hydrodynamics or microstructural heterogeneity. This study explores a physically grounded continuum model that captures how these factors shape conductivity spectra. Nonlinear thermodynamics and linearised dynamics of a viscous electrolyte and compressible, elastic polymer network are coupled under the forcing of an oscillatory electric field. The model is solved in a one-dimensional spatially periodic unit cell, reporting conductivity and dielectric permittivity spectra, including Nyquist representations. Whereas rigid microstructures exhibit ion-diffusion-controlled relaxation, which manifests as a low-frequency dielectric ‘constant’, hydrodynamic and elastic forces contribute to a strongly diverging dielectric permittivity at low frequencies for heterogeneous anionic microstructures. The model also captures distinctive characteristics of experimentally reported impedance spectra for films bearing alternating layers of cationic and anionic charge, again highlighting the role of coupled hydrodynamic, elastic and electrical forces. Sufficiently thin and highly charged bilayers exhibit a notably low high-frequency conductivity. This is explained by strong low-frequency electrostatic polarisation and counter-ion release. The one-dimensional solutions computed herein provide a foundation for much more challenging computations in two and three dimensions.

A xenogeneic extracellular matrix-based 3D printing scaffold modified by ceria nanoparticles for craniomaxillofacial hard tissue regeneration via osteo-immunomodulation

Hard tissue engineering scaffolds especially 3D printed scaffolds were considered an excellent strategy for craniomaxillofacial hard tissue regeneration, involving crania and facial bones and teeth. Porcine treated dentin matrix (pTDM) as xenogeneic extracellular matrix has the potential to promote the stem cell differentiation and mineralization as it contains plenty of bioactive factors similar with human-derived dentin tissue. However, its application might be impeded by the foreign body response induced by the damage-associated molecular patterns of pTDM, which would cause strong inflammation and hinder the regeneration. Ceria nanoparticles (CNPs) show a great promise at protecting tissue from oxidative stress and influence the macrophages polarization. Using 3D-bioprinting technology, we fabricated a xenogeneic hard tissue scaffold based on pTDM xenogeneic TDM-polycaprolactone (xTDM/PCL) and we modified the scaffolds by CNPs (xTDM/PCL/CNPs). Through series of in vitro verification, we found xTDM/PCL/CNPs scaffolds held promise at up-regulating the expression of osteogenesis and odontogenesis related genes including collagen type 1, Runt-related transcription factor 2 (RUNX2), bone morphogenetic protein-2, osteoprotegerin, alkaline phosphatase (ALP) and DMP1 and inducing macrophages to polarize to M2 phenotype. Regeneration of bone tissues was further evaluated in rats by conducting the models of mandibular and skull bone defects. The in vivo evaluation showed that xTDM/PCL/CNPs scaffolds could promote the bone tissue regeneration by up-regulating the expression of osteogenic genes involving ALP, RUNX2 and bone sialoprotein 2 and macrophage polarization into M2. Regeneration of teeth evaluated on beagles demonstrated that xTDM/PCL/CNPs scaffolds expedited the calcification inside the scaffolds and helped form periodontal ligament-like tissues surrounding the scaffolds.

A quality by design approach to optimise disulfide-linked hyaluronic acid hydrogels

In this study, the disulfide-linked hyaluronic acid (HA) hydrogels were optimised for potential application as a scaffold in tissue engineering through the Quality by Design (QbD) approach. For this purpose, HA was first modified by incorporating the cysteine moiety into the HA backbone, which promoted the formation of disulfide cross-linked HA hydrogel at physiological pH. Utilising a Design of Experiments (DoE) methodology, the critical factors to achieve stable biomaterials, i.e. the degree of HA substitution, HA molecular weight, and coupling agent ratio, were explored. To establish a design space, the DoE was performed with 65 kDa, 138 kDa and 200 kDa HA and variable concentrations of coupling agent to optimise conditions to obtain HA hydrogel with improved rheological properties. Thus, HA hydrogel with a 12 % degree of modification, storage modulus of ≈2321 Pa and loss modulus of ≈15 Pa, was achieved with the optimum ratio of coupling agent. Furthermore, biocompatibility assessments in C28/I2 chondrocyte cells demonstrated the non-toxic nature of the hydrogel, underscoring its potential for tissue regeneration. Our findings highlight the efficacy of the QbD approach in designing HA hydrogels with tailored properties for biomedical applications.

A Mesoporous Silica-Loaded Multi-Functional Hydrogel Enhanced Tendon Healing via Immunomodulatory and Pro-Regenerative Effects.

Tendon injuries are pervasive orthopedic injuries encountered by the general population. Nonetheless, recovery after severe injuries, such as Achilles tendon injury, is limited. Consequently, there is a pressing need to devise interventions, including biomaterials, that foster tendon healing. Regrettably, tissue engineering treatments have faced obstacles in crafting appropriate tissue scaffolds and efficacious nanomedical approaches. To surmount these hurdles, an innovative injectable hydrogel (CP@SiO2), comprising puerarin and chitosan through in situ self-assembly, is pioneered while concurrently delivering mesoporous silica nanoparticles for tendon healing. In this research, CP@SiO2 hydrogel is employed for the treatment of Achilles tendon injuries, conducting extensive in vivo and in vitro experiments to evaluate its efficacy. This reults demonstrates that CP@SiO2 hydrogel enhances the proliferation and differentiation of tendon-derived stem cells, and mitigates inflammation through the modulation of macrophage polarization. Furthermore, using histological and behavioral analyses, it is found that CP@SiO2 hydrogel can improve the histological and biomechanical properties of injured tendons. This findings indicate that this multifaceted injectable CP@SiO2 hydrogel constitutes a suitable bioactive material for tendon repair and presents a promising new strategy for the clinical management of tendon injuries.

Physicochemical and biological characterization of propolis-loaded composite polyamide-6/soybean protein nanofibers for wound healing applications

Dressings are pivotal in aiding wound recovery, yet they are burdened by significant constraints. In addition to possessing antibacterial properties, the effectiveness of a wound dressing must be rigorously assessed for its potential utility across diverse medical applications. Propolis (Pro) is widely acknowledged for its antioxidant, antibacterial, and anti-inflammatory properties, positioning it as a promising candidate for wound healing and tissue engineering applications. This study presents a novel composite nanofiber (NF) material comprising polyamide-6 (PA6) and soybean protein as matrix components, incorporating Pro as a payload. We aimed to mimic the extracellular matrix, thus promotion the proliferation and adhesion of mouse embryonic fibroblast cells (NIH3T3) on the scaffold's surface. The morphology and composition of the NFs, examined through scanning electron microscopy (SEM) imaging and Fourier-transform infrared (FTIR) spectroscopy. The Pro-loaded fibers exhibited diameters ranging from 102 to 270 nm. Notably, the NFs demonstrated a dose-dependent increase in porosity, water vapor transmission rate, and fluid uptake capacity. However, the hydrophilic categorized nanofibers (NFs) did not exhibit a concentration-dependent effect on contact angle measurements. After a 15-day period, the Pro-loaded fibers experienced degradation within the range of 39–53 %. Using UV–visible spectrophotometry, the amount of pro released was measured. The rates of release were found to be 29.93 %, 41.02 %, and 60.06 % within 24 h for PA6/Soy/Pro5 %, PA6/Soy/Pro10 %, and PA6/Soy/Pro20 % NFs, respectively. Importantly, our study showcased the significant inhibitory effects of Pro-loaded fibers on the growth of E. coli and S. aureus, with inhibition increasing proportionally with higher Pro concentrations. This observation underscores the potential of Pro-based composite NFs as effective antimicrobial agents for wound dressings and tissue scaffolds. Furthermore, the biocompatibility of the fabricated nanofibrous mats was confirmed through the MTT test, affirming the non-toxic nature of all formulations. SEM imaging further demonstrated the optimal adhesion of cells on the NFs, confirming the findings of the MTT test and highlighting the suitability of Pro-loaded NFs for cell attachment and proliferation.

Elderberry (Sambucus nigra) and hawthorn (Crataegus oxyacantha) extract additives in carboxymethyl chitosan scaffolds for osteochondral tissue engineering applications

Elderberry (<i>Sambucus nigra</i>) and hawthorn (<i>Crataegus oxyacantha</i>) extract additives in carboxymethyl chitosan scaffolds for osteochondral tissue engineering applications

Copper substituted hydroxyapatite reinforced gelatin/polyvinyl alcohol/silk fibre-based scaffold for bone tissue engineering application

In order to restore the function of the damaged tissues, it is essential to find suitable ways which are capable of customizing tissue engineering constructs for each patient. The present study presents the hydrothermal synthesis of copper hydroxyapatite (Cu-HAP), as well as the electrospinning fabrication of gelatin/PVA/silk fibre-Cu-HAP scaffolds. The fabricated scaffold was characterized using XRD, FT-IR, SEM-EDAX in order to confirm the phase formation, functional group, surface topography and elemental composition respectively. The gelatin-PVA-silk fibre with 60 wt % Cu-HAP showed highest porosity (99 %) and highest mechanical strength (96. 13 MPa). To fulfil the requirements of bone tissue engineering the biological application such as antimicrobial activity, hemocompatibility, bioactivity and cell-line studies were carried out. Gelatin/PVA/silk fibre with 60 wt % Cu-HAP scaffold showed excellent zone of inhibition (E. coli - 75 ± 1.38 mm, S. aureus - 65 ± 1.40 mm, C. albicans - 68 ± 1.26 mm), good hemocompatibility (1.20 ± 0.06) with human blood and surface was uniformly covered with HAP in bioactivity studies. That the fabricated gelatin-PVA-silk fibre/Cu-HAP could be effective and suitable as a bone graft material.

3D printed kombucha biomaterial as a tissue scaffold and L929 cell cytotoxicity assay

AbstractTissue engineering includes the construction of tissue‐organ scaffold. The advantage of three‐dimensional scaffolds over two‐dimensional scaffolds is that they provide homeostasis for a longer time. The microbial community in Symbiotic culture of bacteria and yeast (SCOBY) can be a source for kombucha (kombu tea) production. In this study, it was aimed to investigate the usage of SCOBY, which produces bacterial cellulose, as a biomaterial and 3D scaffold material. 3D printable biomaterial was obtained by partial hydrolysis of oolong tea and black tea kombucha biofilms. In order to investigate the usage of 3D kombucha biomaterial as a tissue scaffold, “L929 cell line 3D cell culture” was created and cell viability was tested in the biomaterial. At the end of the 21st day, black tea showed 51% and oolong tea 73% viability. The cytotoxicity of the materials prepared by lyophilizing oolong and black tea kombucha beverages in fibroblast cell culture was determined. Black tea IC50 value: 7.53 mg, oolong tea IC50 value is found as 6.05 mg. Fibroblast viability in 3D biomaterial + lyophilized oolong and black tea kombucha beverages, which were created using the amounts determined to these values, were investigated by cell culture Fibroblasts in lyophilized and 3D biomaterial showed viability of 58% in black tea and 78% in oolong tea at the end of the 7th day. In SEM analysis, it was concluded that fibroblast cells created adhesion to the biomaterial. 3D biomaterial from kombucha mushroom culture can be used as tissue scaffold and biomaterial.

Characterization of a full-thickness decellularized and lyophilized human placental membrane for clinical applications.

Allografts derived from live-birth tissue obtained with donor consent have emerged as an important treatment option for wound and soft tissue repairs. Placental membrane derived from the amniotic sac consists of the amnion and chorion, the latter of which contains the trophoblast layer. For ease of cleaning and processing, these layers are often separated with or without re-lamination and the trophoblast layer is typically discarded, both of which can negatively affect the abundance of native biological factors and make the grafts difficult to handle. Thus, a full-thickness placental membrane that includes a fully-intact decellularized trophoblast layer was developed for homologous clinical use as a protective barrier and scaffold in soft tissue repairs. Here, we demonstrate that this full-thickness placental membrane is effectively decellularized while retaining native extracellular matrix (ECM) scaffold and biological factors, including the full trophoblast layer. Following processing, it is porous, biocompatible, supports cell proliferation in vitro, and retains its biomechanical strength and the ability to pass through a cannula without visible evidence of movement or damage. Finally, it was accepted as a natural scaffold in vivo with evidence of host-cell infiltration, angiogenesis, tissue remodelling, and structural layer retention for up to 10 weeks in a murine subcutaneous implant model.

Magnetic carbon nanotubes modified with proteins and hydrophilic monomers: Cytocompatibility, in-vitro toxicity assays and permeation across biological interfaces

Carbon nanotubes are promising materials for biomedical applications like delivery systems and tissue scaffolds. In this paper, magnetic carbon nanotubes (M-CNTs) covered with bovine serum albumin (M-CNTs-BSA) or functionalized with hydrophilic monomers (M-CNTs-HL) were synthesized, characterized, and evaluated concerning their interaction with Caco-2 cells. There is no comparison between these two types of functionalization, and this study aimed to verify their influence on the material's interaction with the cells. Different concentrations of the nanotubes were applied to investigate cytotoxicity, cell metabolism, oxidative stress, apoptosis, and capability to cross biomimetic barriers. The materials showed cytocompatibility up to 100 μg mL−1 and a hemolysis rate below 2 %. Nanotubes' suspensions were allowed to permeate Caco-2 monolayers for up to 8 h under the effect of the magnetic field. Magnetic nanoparticles associated with the nanotubes allowed estimation of permeation through the monolayers, with values ranging from 0.50 to 7.19 and 0.27 to 9.30 × 10−3 μg (equivalent to 0.43 to 6.22 and 0.23 to 9.54 × 10−2 % of the initially estimated mass of magnetic nanoparticles) for cells exposed and non-exposed to the magnets, respectively. Together, these results support that the developed materials are promising for applications in biomedical and biotechnological fields.

Computational fluid dynamics analysis of the fluid environment of 3D printed gradient structure in interfacial tissue engineering

Mass transport properties within three-dimensional (3D) scaffold are essential for tissue regeneration, such as various fluid environmental cues influence mesenchymal stem cells differentiation. Recently, 3D printing has been emerging as a new technology for scaffold fabrication by controlling the scaffold pore geometry to affect cell growth environment. In this study, the flow field within scaffolds in a perfusion system was investigated with uniform structures, single gradient structures and complex gradient structures using computational fluid dynamics (CFD) method. The CFD results from those uniform structures indicate the fluid velocity and fluid shear stress within the scaffold structure increased as the filament diameter increasing, pore width decreasing, pore shape decreased from 90° to 15°, and layer configuration changing from lattice to stagger structure. By assembling those uniform structure as single gradient structures, it is noted that the fluid dynamic characterisation within the scaffold remains the same as the corresponding uniform structures. A complex gradient structure was designed to mimic natural osteochondral tissue by assembly the uniform structures of filament diameter, pore width, pore shape and layer configuration. The results show that the fluid velocity and fluid shear stress within the complex gradient structure distribute gradually increasing and their maximum magnitude were from 1.15 to 3.20 mm/s, and from 12 to 39 mPa, respectively. CFD technique allows the prediction of velocity and fluid shear stress within the designed 3D gradient scaffolds, which would be beneficial for the tissue scaffold development for interfacial tissue engineering in the future.

Architectural differences in photopolymerized PEG-based thiol-acrylate hydrogels enable enhanced mechanical properties and 3D printability

Hydrogels have been widely investigated for applications in the human body due to their tunability and biocompatibility. Nevertheless, their application is still limited by their relatively low mechanical strength relative to load-bearing tissue scaffolds like articular cartilage. In this work, we synthesized hydrogels by combining linear poly(ethylene glycol) dimethacrylate (PEGDMA) with a 3-arm-PEG end-functionalized with thiol. We demonstrate that the combination of thiol-ene click chemistry with a multifunctional crosslinker reduces the crosslink and entanglement density in comparison with the otherwise statistically crosslinked/polymerized PEGDMA, whereby the only viable mode of gelation is through radical propagation or termination at the double bond. The corresponding minimization of topological heterogeneities that arises during thiol-ene crosslinking results in hydrogels with compressive strength in the range of tens of MPa. The molar mass of the linear PEGDMA precursor is readily tunable, unlocking access to a wider range of mechanical properties. We employed photo-mediated crosslinking protocol, which is amenable to advanced processing technologies such as light-based 3D printing techniques. Such advanced fabrication processes offer high precision and control during the generation of customizable macroscopic objects. Simple prototypes were generated using digital light processing (DLP) equipment. We demonstrate that integrating a simple co-macromonomer into a widely employed hydrogel platform can unlock new mechanical regimes and mitigate the inherent brittleness associated with these materials. The simplicity of this approach, coupled with its easy tunability and adaptability to light-based techniques, holds promise for broadening hydrogel applications in tissue engineering. Our findings contribute to advancing materials and methodologies, facilitating enhanced design and fabrication of functional constructs.

Unveiling In situ fibrillation for superior tissue scaffolds with two-phase copolymer microcellular foams

High open-pore content and high mechanical strength are important in Tissue engineering. However, an increase in one property is often at the expense of the other. This study reports a first-of-its-kind study using two-phase copolymers Poly (caprolactone-co-lactic acid) (PLCL) as a compatibilizer, combining in-situ fibrillation and microcellular foaming, thus preparing foams with high open-pore content and high mechanical properties. The porous foam scaffold promotes the adhesion and diffusion of endothelial cells and expedites scaffold endothelialization. Additionally, the enhanced open porosity of the foams augments the effectiveness of drug absorption and release, underscoring its significant potential for practical application.

Unraveling the influence of channel size and shape in 3D printed ceramic scaffolds on osteogenesis

Bone has the capacity to regenerate itself for relatively small defects; however, this regenerative capacity is diminished in critical-size bone defects. The development of synthetic materials has risen as a distinct strategy to address this challenge. Effective synthetic materials to have emerged in recent years are bioceramic implants, which are biocompatible and highly bioactive. Yet nothing suitable for the repair of large bone defects has made the transition from laboratory to clinic. The clinical success of bioceramics has been shown to depend not only on the scaffold's intrinsic material properties but also on its internal porous geometry. This study aimed to systematically explore the implications of varying channel size, shape, and curvature in tissue scaffolds on in vivo bone regeneration outcomes. 3D printed bioceramic scaffolds with varying channel sizes (0.3 mm to 1.5 mm), shapes (circular vs rectangular), and curvatures (concave vs convex) were implanted in rabbit femoral defects for 8 weeks, followed by histological evaluation. We demonstrated that circular channel sizes of around 0.9 mm diameter significantly enhanced bone formation, compared to channel with diameters of 0.3 mm and 1.5 mm. Interestingly, varying channel shapes (rectangular vs circular) had no significant effect on the volume of newly formed bone. Furthermore, the present study systematically demonstrated the beneficial effect of concave surfaces on bone tissue growth in vivo, reinforcing previous in silico and in vitro findings. This study demonstrates that optimizing architectural configurations within ceramic scaffolds is crucial in enhancing bone regeneration outcomes. Statement of significanceDespite the explosion of work on developing synthetic scaffolds to repair bone defects, the amount of new bone formed by scaffolds in vivo remains suboptimal. Recent studies have illuminated the pivotal role of scaffolds’ internal architecture in osteogenesis. However, these investigations have mostly remained confined to in silico and in vitro experiments. Among the in vivo studies conducted, there has been a lack of systematic analysis of individual architectural features. Herein, we utilized bioceramic 3D printing to conduct a systematic exploration of the effects of channel size, shape, and curvature on bone formation in vivo. Our results demonstrate the significant influence of channel size and curvature on in vivo outcomes. These findings provide invaluable insights into the design of more effective bone scaffolds.

3D Poly (L-lactic acid) fibrous sponge with interconnected porous structure for bone tissue scaffold

Large bone defects, often resulting from trauma and disease, present significant clinical challenges. Electrospun fibrous scaffolds closely resembling the morphology and structure of natural ECM are highly interested in bone tissue engineering. However, the traditional electrospun fibrous scaffold has some limitations, including lacking interconnected macropores and behaving as a 2D scaffold. To address these challenges, a sponge-like electrospun poly(L-lactic acid) (PLLA)/polycaprolactone (PCL) fibrous scaffold has been developed by an innovative and convenient method (i.e., electrospinning, homogenization, progen leaching and shaping). The resulting scaffold exhibited a highly porous structure (overall porosity = 85.9 %) with interconnected, regular macropores, mimicking the natural extracellular matrix. Moreover, the incorporation of bioactive glass (BG) particles improved the hydrophilicity (water contact angle = 79.7°) and biocompatibility and promoted osteoblast cell growth. In-vitro 10-day experiment revealed that the scaffolds led to high cell viability. The increment of the proliferation rates was 195.4 % at day 7 and 281.6 % at day 10. More importantly, Saos-2 cells could grow, proliferate, and infiltrate into the scaffold. Therefore, this 3D PLLA/PCL with BG sponge holds great promise for bone defect repair in tissue engineering applications.

SPINNED: Simulation-based physics-informed neural network for deconvolution of dynamic susceptibility contrast MRI perfusion data.

To propose the simulation-based physics-informed neural network for deconvolution of dynamic susceptibility contrast (DSC) MRI (SPINNED) as an alternative for more robust and accurate deconvolution compared to existing methods. The SPINNED method was developed by generating synthetic tissue residue functions and arterial input functions through mathematical simulations and by using them to create synthetic DSC MRI time series. The SPINNED model was trained using these simulated data to learn the underlying physical relation (deconvolution) between the DSC-MRI time series and the arterial input functions. The accuracy and robustness of the proposed SPINNED method were assessed by comparing it with two common deconvolution methods in DSC MRI data analysis, circulant singular value decomposition, and Volterra singular value decomposition, using both simulation data and real patient data. The proposed SPINNED method was more accurate than the conventional methods across all SNR levels and showed better robustness against noise in both simulation and real patient data. The SPINNED method also showed much faster processing speed than the conventional methods. These results support that the proposed SPINNED method can be a good alternative to the existing methods for resolving the deconvolution problem in DSC MRI. The proposed method does not require any separate ground-truth measurement for training and offers additional benefits of quick processing time and coverage of diverse clinical scenarios. Consequently, it will contribute to more reliable, accurate, and rapid diagnoses in clinical applications compared with the previous methods including those based on supervised learning.