Scaffold Degradation Research Articles

3D Printed Chondrogenic Functionalized PGS Bioactive Scaffold for Cartilage Regeneration.

Tissue engineering is emerging as a promising approach for cartilage regeneration and repair. Endowing scaffolds with cartilaginous bioactivity to obtain bionic microenvironment and regulating the matching of scaffold degradation and regeneration play a crucial role in cartilage regeneration. Poly(glycerol sebacate) (PGS) is a representative thermosetting bioelastomer known for its elasticity, biodegradability, and biocompatibility and is widely used in tissue engineering. However, the modification and drug loading of the PGS scaffold is still a key challenge due to its high temperature curing conditions and limited reactive groups, which seriously hinders its further functional application. Here, a simple versatile new strategy of super swelling-absorption and cross-linked networks locking is presented to successfully create the 3Dprinted PGS-CS/Gel scaffold for the first time based on FDA-approved PGS, gelatin (Gel) and chondroitin sulfate (CS). The PGS-CS/Gel scaffold exhibits the desirable synergistic properties of well-organized hierarchical structures, excellent elasticity, improved hydrophilicity, and cartilaginous bioactivity, which can promote the adhesion, proliferation, and migration of chondrocytes. Importantly, the rate of cartilage regeneration can be well-matched with degradation of PGS-CS/Gel scaffold, and achieve uniform and mature cartilage tissue without scaffold residual. The bioactive scaffold can successfully repair cartilage in a rabbit trochlear groove defect model indicating a promising prospect of clinical transformation.

Photopolymers Based on Boronic Esters for the Enhanced Degradation of 3D-Printed Scaffolds

Photopolymers Based on Boronic Esters for the Enhanced Degradation of 3D-Printed Scaffolds

Observation of discrepancy between the degradation of polymer scaffolds in vitro and in vivo according to high-resolution ultrasound technique

Biocompatible, biodegradable polymers are actively used as drug delivery systems and as tissue engineering scaffolds. The hydrothermal aging of polymers, including degradation of the microstructure and changes of mechanical properties directly depends on environmental conditions. In vitro studies in a model media cannot contain and describe all the factors influencing the polymer degradation in a living organism. It seems promising to study the processes of changes in the microstructure and elastic properties of polymer implants invivo in dynamics. Here, we present data from the application of new experimental equipment for high-resolution ultrasound imaging of polymer degradation in vivo. Ultrasonic results include images of the transformation of volumetric microstructure and changes in elastic properties in dynamics. The method was verified on a rapidly degradable polymer poly(D,L-lactide-co-glycolide). We assess and compare the evolution of volume microstructure, elastic properties and molecular weight of the polymer weekly for 1.5 months of incubation in vitro and in vivo. We found that the in vivo degradation process occurs with a delay of 2 weeks compared to the hydrothermal aging invitro.

A bioresponsive diselenide-functionalized hydrogel with cascade catalytic activities for enhanced local starvation- and hypoxia-activated melanoma therapy

Glutathione (GSH) consumption-enhanced cancer therapies represent important potential cancer treatment strategies. Herein, we developed a new multifunctional diselenide-crosslinked hydrogel with glutathione peroxidase (GPx)-like catalytic activity for GSH depletion-enhanced glucose oxidase (GOx)-mediated tumor starvation and hypoxia-activated chemotherapy. By increasing acid and H2O2 during GOx-induced tumor starvation, the degradation of the multiresponsive scaffold could be promoted, which led to accelerated release of the loaded drugs. Meanwhile, the overproduced H2O2 led to accelerated intracellular GSH consumption under the cascade catalysis of small molecular selenides released from the degraded hydrogel, further enhancing the curative effect of in situ H2O2 and subsequent multimodal cancer treatment. Following the GOx-induced amplification of hypoxia, tirapazamine (TPZ) was transformed into the highly toxic benzotriazinyl radical (BTZ·), exhibiting enhanced antitumor activity. This GSH depletion-augmented cancer treatment strategy effectively boosted GOx-mediated tumor starvation and activated the hypoxia drug, leading to significantly enhanced local anticancer efficacy. Statement of significanceThere has been a growing interest in depleting intracellular GSH as a potential strategy for improving ROS-based cancer therapy. Herein, a bioresponsive diselenide-functionalized dextran-based hydrogel with GPx-like catalytic activity was developed for GSH consumption-enhanced local starvation- and hypoxia-activated melanoma therapy. Results showed that the overproduced H2O2 led to accelerated intracellular GSH consumption under the cascade catalysis of small molecular selenides released from the degraded hydrogel, further enhancing the curative effect of in situ H2O2 and subsequent multimodal cancer treatment.

Enhancement of Scaffold In Vivo Biodegradability for Bone Regeneration Using P28 Peptide Formulations.

The field of bone tissue engineering has shown a great variety of bone graft substitute materials under development to date, with the aim to reconstruct new bone tissue while maintaining characteristics close to the native bone. Currently, insufficient scaffold degradation remains the critical limitation for the success of tailoring the bone formation turnover rate. This study examines novel scaffold formulations to improve the degradation rate in vivo, utilising chitosan (CS), hydroxyapatite (HAp) and fluorapatite (FAp) at different ratios. Previously, the P28 peptide was reported to present similar, if not better performance in new bone production to its native protein, bone morphogenetic protein-2 (BMP-2), in promoting osteogenesis in vivo. Therefore, various P28 concentrations were incorporated into the CS/HAp/FAp scaffolds for implantation in vivo. H&E staining shows minimal scaffold traces in most of the defects induced after eight weeks, showing the enhanced biodegradability of the scaffolds in vivo. The HE stain highlighted the thickened periosteum indicating a new bone formation in the scaffolds, where CS/HAp/FAp/P28 75 µg and CS/HAp/FAp/P28 150 µg showed the cortical and trabecular thickening. CS/HAp/FAp 1:1 P28 150 µg scaffolds showed a higher intensity of calcein green label with the absence of xylenol orange label, which indicates that mineralisation and remodelling was not ongoing four days prior to sacrifice. Conversely, double labelling was observed in the CS/HAp/FAp 1:1 P28 25 µg and CS/HAp/FAp/P28 75 µg, which indicates continued mineralisation at days ten and four prior to sacrifice. Based on the HE and fluorochrome label, CS/HAp/FAp 1:1 with P28 peptides presented a consistent positive osteoinduction following the implantation in the femoral condyle defects. These results show the ability of this tailored formulation to improve the scaffold degradation for bone regeneration and present a cost-effective alternative to BMP-2.

Effect of Magnesium as Biomaterial in Biodegrdation

Since many years ago, the study of engineering materials—which includes metal alloys, composites, polymers, ceramics, and metallic glasses—has advanced significantly, particularly in the area of biomaterials. Due to their excellent biocompatibility and unique mechanical qualities, alloys derived on magnesium (Mg) now have a wide array of uses in the biomedical sector. By combining Mg with other elements including nanoparticles, polymers, Zinc, Yttrium and Manganese are included with capability to perform suitable reactions. Addictive manufacturing allows the porosity of the scaffolds to be adjusted, allowing for fine-tuning of the scaffold degradation performance and cell response. Specialized equipment will be required to print magnesium in an inert atmosphere while maintaining safe material handling. As a result, due to inherent characteristics of magnesium mixes, such as a higher vapour pressure and a stronger inclination to oxidize, the additive manufacture of disposable magnesium-based implants presents certain challenges. Inadvertent degradation, structural failure, hydrogen evolution, alkalization, and cytotoxicity are caused by the high corrosion rate of Mg-based implants. A number of methods, such as the design of a magnesium alloy and the alteration of the surface properties, are employed to tailor the degradation rate since it is envisaged that biodegradable Mg-based implants will demonstrate regulated degradation and satisfy the needs of specific applications. Biodegradation mechanism along with its controlling aspects and improvement measures with respect to biodegradation are reviewed in this paper.

Feasibility of repairing skin defects by VEGF165 gene-modified iPS-HFSCs seeded on a 3D printed scaffold containing astragalus polysaccharide.

The preparation of biodegradable scaffolds loaded with cells and cytokine is a feature of tissue-engineered skin. IPSCs-based tissue-engineered skin treatment for wound repair is worth exploring. Healthy human skin fibroblasts were collected and reprogrammed into iPSCs. After gene modification and induction, CK19+ /Integrinβ1+ /CD200+ VEGF165 gene-modified iPS-HFSCsGFP were obtained and identified by a combination of immunofluorescence and RT-qPCR. Astragalus polysaccharide-containing 3D printed degradable scaffolds were prepared and co-cultured with VEGF165 gene-modified iPS-HFSCsGFP , and the biocompatibility and spatial structure of the tissue-engineered skin was analysed by cell counting kit-8 (CCK8) assay and scanning electron microscopy. Finally, the tissue-engineered skin was transplanted onto the dorsal trauma of nude mice, and the effect of tissue-engineered skin on the regenerative repair of total skin defects was evaluated by a combination of histology, immunohistochemistry, immunofluorescence, RT-qPCR, and in vivo three-dimensional reconstruction under two-photon microscopy. CK19+ /Integrinβ1+ /CD200+ VEGF165 gene-modified iPS-HFSCsGFP , close to the morphology and phenotype of human-derived hair follicle stem cells, were obtained. The surface of the prepared 3D printed degradable scaffold containing 200 μg/mL astragalus polysaccharide was enriched with honeycomb-like meshwork, which was more conducive to the proliferation of the resulting cells. After tissue-engineered skin transplantation, combined assays showed that it promoted early vascularization, collagen and hair follicle regeneration and accelerated wound repair. VEGF165 gene-modified iPS-HFSCsGFP compounded with 3D printed degradable scaffolds containing 200 μg/mL astragalus polysaccharide can directly and indirectly participate in vascular, collagen, and hair follicle regeneration in the skin, achieving more complete structural and functional skin regenerative repair.

Additive Manufacturing of Polymer/Bioactive Glass Scaffolds for Regenerative Medicine: A Review.

Tissue engineering (TE) is a branch of regenerative medicine with enormous potential to regenerate damaged tissues using synthetic grafts such as scaffolds. Polymers and bioactive glasses (BGs) are popular materials for scaffold production because of their tunable properties and ability to interact with the body for effective tissue regeneration. Due to their composition and amorphous structure, BGs possess a significant affinity with the recipient's tissue. Additive manufacturing (AM), a method that allows the creation of complex shapes and internal structures, is a promising approach for scaffold production. However, despite the promising results obtained so far, several challenges remain in the field of TE. One critical area for improvement is tailoring the mechanical properties of scaffolds to meet specific tissue requirements. In addition, achieving improved cell viability and controlled degradation of scaffolds is necessary to ensure successful tissue regeneration. This review provides a critical summary of the potential and limitations of polymer/BG scaffold production via AM covering extrusion-, lithography-, and laser-based 3D-printing techniques. The review highlights the importance of addressing the current challenges in TE to develop effective and reliable strategies for tissue regeneration.

Recent Developments in Engineered Magnesium Scaffolds for Bone Tissue Engineering.

Significant attention has been drawn in recent years to develop porous scaffolds for tissue engineering. In general, porous scaffolds are used for non-load bearing applications. However, various metallic scaffolds have been investigated extensively for hard tissue repair due to their favorable mechanical and biological properties. Stainless steel (316L) and titanium (Ti) alloys are the most commonly used material for metallic scaffolds. Although stainless steel and Ti alloys are employed as scaffold materials, it might result in complications such as stress shielding, local irritation, interference with radiography, etc. related to the permanent implants. To address the above-mentioned complications, degradable metallic scaffolds have emerged as a next generation material. Among the all metallic degradable scaffold materials, magnesium (Mg) based material has gained significant attention owing to its advantageous mechanical properties and excellent biocompatibility in a physiological environment. Therefore, Mg based materials can be projected as load bearing degradable scaffolds, which can provide structural support toward the defected hard tissue during the healing period. Moreover, advanced manufacturing techniques such as solvent cast 3D printing, negative salt pattern molding, laser perforation, and surface modifications can make Mg based scaffolds promising for hard tissue repair. In this article, we focus on the advanced fabrication techniques which can tune the porosity of the degradable Mg based scaffold favorably and improve its biocompatibility.

Porous iron-reinforced polylactic acid TPMS bio-scaffolds: Interlocking reinforcement and synergistic degradation

Porous materials are expected to bring a positive impact on enhancing interfaces and mechanics due to their unique pore networks. Herein, porous iron (pFe) was used as the reinforcing phase to strengthen poly (lactic acid) (PLA) matrix, and PLA/pFe scaffolds were prepared via selective laser sintering (SLS) technique. Scaffold models were constructed using triply periodic minimal surfaces (TPMS) and the optimal porosity was obtained by mechanical evaluation. The results showed that pFe incorporation significantly improved mechanical properties, especially for PLA/5pFe scaffold, which was 121% higher than that of PLA scaffold. It may be that molten PLA molecules penetrate the pore network of pFe particles, forming spatial interlocks and encapsulations, thereby improving the efficiency of stress transfer. In addition, a chemical catalytic cycle is expected to be formed between PLA hydrolysis and pFe degradation to promote the degradation of composite scaffolds. Moreover, the composite scaffold also showed good biomineralization and cytocompatibility in vitro. These properties make the PLA/pFe composite scaffold promising for bone tissue engineering applications.

Evaluation of heat transfer in porous scaffolds under cryogenic treatment: a numerical study.

The present work had evaluated the effect of cryogenic treatment (233K) on the degradation of polymeric biomaterial using a numerical model. The study on effect of cryogenic temperature on mechanical properties of cell-seeded biomaterials is very limited. However, no study had reported material degradation evaluation. Different structures of silk-fibroin-poly-electrolyte complex (SFPEC) scaffolds had been designed by varying hole distance and hole diameter, with reference to existing literature. The size of scaffolds were maintained at 5 [Formula: see text] 5 mm2. Current study evaluates the effect of cryogenic temperature on mechanical properties (corelated to degradation) of scaffold. Six parameters related to scaffold degradation: heat transfer, deformation gradient, stress, strain, strain tensor, and displacement gradient were analyzed for three different cooling rates (- 5K/min, - 2K/min, and - 1K/min). Scaffold degradation had been evaluated in the presence of water and four different concentrations of cryoprotectant solution. Heat distribution at various points (points_base, point_wall and point_core) on the region of interest (ROI) was found similar for different cooling rates of the system. Thermal stress was found developing proportional to cooling rate, which leads to minimal variation in thermal stress over time. Strain tensor was found gradually decreasing due to attenuating response of deformation gradient. In addition to that, dipping down of cryogenic temperature had prohibited the movement of molecules in the crystalline structure which had restricting the displacement gradient. It was found that uniform distribution of desired heat at different cooling rates has the ability to minimize the responses of other scaffold degradation parameters. It was found that the rates of change in stress, strain, and strain tensor were minimal at different concentrations of cryoprotectant. The present study had predicted the degradation behavior of PEC scaffold under cryogenic temperature on the basis of explicit mechanical properties.

3D Printing of Porous Degradable Scaffolds with Polylactic Acid‐Loaded Bioactive Glass and Calcium Sulfate Hemihydrate for Bone Defect Repair

AbstractRepair of bone defects, especially critical‐sized bone defects, remains a major clinical problem, and bone nonunion is the biggest challenge. Herein, melt‐extrusion 3D printing is applied to prepare biodegradable composite scaffolds containing bioactive glass (BAG), calcium sulfate hemihydrate (CSH), and polylactic acid (PLA). The compressive strength of scaffolds is similar to that of human bone tissue. In vitro and in vivo experiments show that the scaffolds have good biocompatibility. The scaffold can maintain the biomechanical stability of the bone defect area during the follow‐up period of 20 weeks and has no damage to liver and kidney in animal experiments. Scaffold degradation is accompanied by trabecular bone and vessel neogenesis. While the PLA group and control group cannot carry out effective bone defect repair, the bone defect repair effect of the PLA‐CSH‐BAG group is satisfactory. In conclusion, the biodegradable porous scaffold has been proposed as a safe and effective approach for the repair of bone defects.

3D-printing-assisted synthesis of paclitaxel-loaded niosomes functionalized by cross-linked gelatin/alginate composite: Large-scale synthesis and in-vitro anti-cancer evaluation

Breast cancer is one of the most lethal cancers, especially in women. Despite many efforts, side effects of anti-cancer drugs and metastasis are still the main challenges in breast cancer treatment. Recently, advanced technologies such as 3D-printing and nanotechnology have created new horizons in cancer treatment. In this work, we report an advanced drug delivery system based on 3D-printed gelatin-alginate scaffolds containing paclitaxel-loaded niosomes (Nio-PTX@GT-AL). The morphology, drug release, degradation, cellular uptake, flow cytometry, cell cytotoxicity, migration, gene expression, and caspase activity of scaffolds, and control samples (Nio-PTX, and Free-PTX) were investigated. Results demonstrated that synthesized niosomes had spherical-like, in the range of 60–80 nm with desirable cellular uptake. Nio-PTX@GT-AL and Nio-PTX had a sustained drug release and were biodegradable. Cytotoxicity studies revealed that the designed Nio-PTX@GT-AL scaffold had <5 % cytotoxicity against non-tumorigenic breast cell line (MCF-10A) but showed 80 % cytotoxicity against breast cancer cells (MCF-7), which was considerably more than the anti-cancer effects of control samples. In migration evaluation (scratch-assay), approximately 70 % reduction of covered surface area was observed. The anticancer effect of the designed nanocarrier could be attributed to gene expression regulation, where a significant increase in the expression and activity of genes promoting apoptosis (CASP-3, CASP-8, and CASP-9) and inhibiting metastasis (Bax, and p53) and a remarkable decrease in metastasis-enhancing genes (Bcl2, MMP-2, and MMP-9) were observed. Also, flow cytometry results declared that Nio-PTX@GT-AL reduced necrosis and increased apoptosis considerably. The results of this study prove that employing 3D-printing and niosomal formulation is an effective approach in designing nanocarriers for efficient drug delivery applications.

Preparation and Characterization of EDC/NHS Crosslinked Collagen Scaffold from the Scales of Cyprinus carpio (Common Carp)

Aquaculture is the fast-growing industry and, consequently, fish waste management is becoming a rising concern. Fish scale trash contains collagen as a biomaterial which offers excellent properties such as biocompatibility, biodegradability, porosity, low toxicity, cell adhesion and water absorption capacity which makes it suitable for biomedical research in the form of scaffolds. But the scaffolds have the limitation of having less stability. To overcome this shortcoming, collagen scaffolds can either be modified by chemical or physical treatments such as crosslinking with suitable polymers and dehydrothermal treatment, respectively. In the present study, extraction of fish collagen from the scales of Cyprinus carpio was performed followed by crosslinking with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) & N-hydroxysuccinimide (NHS). Comparative characterization was done by techniques such as ATR-FTIR, FESEM and TGA to analyse the chemical composition, surface morphology and thermal degradation of fish collagen scaffold (CS) with EDC/NHS crosslinked collagen scaffold (EDC/NHS-CS). Crosslinked collagen scaffold’s antimicrobial activity was also determined with agar well diffusion assay by using S. aureus strain of bacteria and cytotoxicity on mouse fibroblast cells (NIH/3T3) by MTT assay. Moreover, the biomedical industry wants to shift to sustainable approaches and fish collagen-based scaffolds may prove to be a potential source in tissue engineering. And thus, also help in the management of fish waste.

Investigation into Biocompatibility and In Vitro Osteogenic Differentiation Ability of New Degradable Polymer Material (Poly-glycerolsebacate-maleic Anhydride) Combined with Nano-Hydroxyapatite Scaffolds

This work explored the biocompatibility and In Vitro osteogenic differentiation ability of new degradable polymer scaffold to provide some references for the research focusing on applying the scaffold for osseous tissue engineering. Polyglycerolsebacate-maleic anhydride (PGS-M) and Nano-hyproxyapatite (n-HA) were utilized to prepare a new scaffold, which was called PGS-M/n-HA herein. Besides, scanning electron microscope (SEM) was employed to observe the morphology and porosity of the PGS-M/n-HA, and its In Vitro degradation rate and mechanical property (MP) were analyzed. Human bone marrow mesenchymal stem cells (HBMSCs) (Ctrl group), osteoblast inducing conditional media (OICM group), PGS-M/n-HA group, and PGS-M/n-HA combining with OICM (OICM+PGS-M/n-HA group) were cultured. After that, the differences in cell adhesion rate, viability, and alkaline phosphatase (AKP) activity were compared and analyzed. It was demonstrated that porosities of PGS-M and PGS-M/n-HA declined while the constrained modulus increased. Based on those in the Ctrl group, the cell viability and AKP activity in the OICM group were enhanced. In contrast to those in PGS-M/n-HA group, cell adhesion rate and AKP activity were both enhanced in the OICM+PGS-M/n-HA group. Therefore, it suggested that PGS-M/n-HA scaffold possessed high degradability, MP, and biocompatibility, and could induce the differentiation of HBMSCs into osteoblasts.

Preliminary study of degradation of a pNaSS-grafted PCL scaffold in synthetic media: a potential candidate patch for early intrauterine cover-age of myelomeningoceles

We present an electrospun polycaprolactone membrane engrafted with bioactive polymers (pNaSS), designed as a candidate patch for intrauterine coverage of fetal myelomeningoceles, early in pregnancy. The biodegradation of the patch was studied over 90 days in different media (0.15 M NaCl, 1.5 M NaCl solution, PBS and 2% urea), approaching the composition of amniotic fluid. The stability of the electrospun membranes and of the polymer grafting was analyzed by scanning electron microscopy, differential scanning calorimetry, colorimetry and permeability test. The results show a degradation of the membrane after 90 days in 0.15 M NaCl solution in terms of morphology but in terms of grafting a decrease of grafting degree was shown in urea solution. Despite morphology and grafting degree analysis showed a beginning of degradation after 90 days in different media, the membrane remained watertight at 90 days with all media. This preliminary study shows the structural integrity of the membranes and stability of the grafting onto PCL scaffolds.

Biophysical cues of bone marrow-inspired scaffolds regulate hematopoiesis of hematopoietic stem and progenitor cells

Hematopoietic stem cells (HSCs) are adult multipotential stem cells with the capacity to differentiate into all blood cells and immune cells, which are essential for maintaining hematopoietic homeostasis throughout the lifespan and reconstituting damaged hematopoietic system after myeloablation. However, the clinical application of HSCs is hindered by the imbalance of its self-renewal and differentiation during in vitro culture. Considering the fact that HSC fate is uniquely determined by natural bone marrow microenvironment, various elaborate cues in this hematopoietic micro-niche provide an excellent reference for the regulation of HSCs.Inspired by the bone marrow extracellular matrix (ECM) network, we designed degradable scaffolds by orchestrating the physical parameters to investigate the decoupling effects of Young's modulus and pore size of three-dimensional (3D) matrix materials on the fate of hematopoietic stem and progenitor cells (HSPCs). We ascertained that the scaffold with larger pore size (80 μm) and higher Young's modulus (70 kPa) was more favorable for HSPCs proliferation and the maintenance of stemness related phenotypes. Through in vivo transplantation, we further validated that scaffolds with higher Young's modulus were more propitious in maintaining the hematopoietic function of HSPCs. We systematically screened an optimized scaffold for HSPC culture which could significantly improve the cell function and self-renewal ability compared with traditional two-dimensional (2D) culture. Together, these results indicate the important role of biophysical cues in regulating HSC fate and pave the way for the parameter design of 3D HSC culture system.

Abstract 2000: Injectable alginate scaffolds for the delivery of minocycline for the treatment of glioblastoma

Abstract Glioblastoma Multiforme (GBM) is a Grade IV malignant brain cancer that is associated with a high recurrence and low survival rate amongst affected patients. Despite advances in the different methods of therapy, the prognosis for GBM has not improved through the years and, thus, alternative treatment methods for GBM are needed. Minocycline (MINO) is known as a semi-synthetic tetracycline that serves as an antibiotic and has also been shown to be able to suppress angiogenesis for GBM treatment. Collected from brown seaweed, alginate is a biodegradable polysaccharide that can be used to form a hydrogel for drug delivery due to its biocompatibility properties. Injectable alginate scaffolds may be a promising component for an adjuvant treatment method against GBM as the injectability property of the scaffold will allow for the site of interest to be filled precisely after tumor resection. The objective of this study is to develop injectable alginate scaffolds for the delivery of MINO for the treatment of GBM. The effects of the concentration of sodium alginate (SA) and calcium carbonate (CaCO3) (i.e., 0.75, 1.00, 1.50, and 2.00 wt./vol.%) with a 0.25 wt./vol.% of glucono-delta lactone (GDL) on the pH, gelation time, dimensions, degradation, and drug release kinetics of alginate scaffolds were investigated. Injectable alginate scaffolds were fabricated by dissolving SA and CaCO3 (1:1) in water, homogenized with GDL for 20 sec., and then injected into a 24-well plate to develop uniform scaffolds. Their properties were evaluated by testing pH values via a pH meter, timing gelation with a digital timer, utilizing a digital microcaliper to investigate dimensions, an analytical scale to evaluate the mass of dried scaffolds to determine scaffold degradation, and evaluating the release rate of MINO using a microplate reader at a wavelength of 350 nm. As the concentration of SA and CaCO3 increased, an increase in pH, gelation time, and overall stability of the scaffold were observed. All four concentrations of SA and CaCO3 tested resulted in scaffolds with desired pH and workable gelation time; however, the 1 wt./vol.% group may be the most ideal as an optimal pH was reached after 10 minutes and the gelation time for these scaffolds was ~8 minutes. Lower concentration scaffolds (0.75 and 1.00 wt./vol.%) degraded faster in comparison to those made with higher concentrations. Drug release kinetics data revealed that the scaffolds can sustain short term release but could be improved by incorporating the drug into micro or nanoparticles before incorporation into the scaffolds. In conclusion, the injectable alginate scaffolds developed in this study may be promising biomaterials for the delivery of drugs for GBM treatment. Citation Format: Kaitlyn D. Ybáñez, Marco A. Arriaga, Rene N. Rico, Theresia Rookstool, Sue Anne Chew. Injectable alginate scaffolds for the delivery of minocycline for the treatment of glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2000.

An injectable, self-healing and degradable hydrogel scaffold as a functional biocompatible material for tissue engineering applications

Injectable hydrogels derived from natural extracellular matrices exhibit excellent adhesion to endothelial cells in vitro and are ideal for many biomedical applications. However, their applicability in vivo is limited by the risk of infection or immunogenicity, and the current injectables also suffer from degradation, viscosity, and drug release. In this study, a multifunctional hydrogel scaffold (COB hydrogels) was constructed by incorporating bioactive glass nanoparticles with a Schiff base crosslinking-based hydrogel composed of carboxymethyl chitosan and oxidized cellulose. The incorporation of nanoparticles not only shortened the gelation time of the COB hydrogels, but also enhanced the performance of the hydrogel in terms of function, such as drug loading capacity. The prepared hydrogels also have self-healing ability, injectability, drug loading and sustained release, antibacterial properties and biocompatibility. In addition, given their no cytotoxicity and mild inflammation in vivo, the hydrogel scaffolds will be important for tissue engineering and drug delivery applications.

Successful restoration of corneal surface integrity with a tissue-engineered allogeneic implant in severe keratitis patients

ObjectivesCorneal diseases are among the main causes of blindness, with approximately 4.6 and 23 million patients worldwide suffering from bilateral and unilateral corneal blindness, respectively. The standard treatment for severe corneal diseases is corneal transplantation. However, relevant disadvantages, particularly in high-risk conditions, have focused the attention on the search for alternatives. MethodsWe report interim findings of a phase I-II clinical study evaluating the safety and preliminary efficacy of a tissue-engineered corneal substitute composed of a nanostructured fibrin-agarose biocompatible scaffold combined with allogeneic corneal epithelial and stromal cells (NANOULCOR). 5 subjects (5 eyes) suffering from trophic corneal ulcers refractory to conventional treatments, who combined stromal degradation or fibrosis and limbal stem cell deficiency, were included and treated with this allogeneic anterior corneal substitute. ResultsThe implant completely covered the corneal surface, and ocular surface inflammation decreased following surgery. Only four adverse reactions were registered, and none of them were severe. No detachment, ulcer relapse nor surgical re-interventions were registered after 2 years of follow-up. No signs of graft rejection, local infection or corneal neovascularization were observed either. Efficacy was measured as a significant postoperative improvement in terms of the eye complication grading scales. Anterior segment optical coherence tomography images revealed a more homogeneous and stable ocular surface, with complete scaffold degradation occurring within 3–12 weeks after surgery. ConclusionsOur findings suggest that the surgical application of this allogeneic anterior human corneal substitute is feasible and safe, showing partial efficacy in the restoration of the corneal surface.