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This article defines immunophenotypes of stromal inflammatory and endothelial cells and fibroblasts 3 months after augmentation of the peri-implant soft tissue using a porcine cross-linked collagen matrix (VCMX). Peri-implant soft tissue samples were obtained from 12 patients at the lining mucosa (LM)-masticatory mucosa (MM) junction before (1) and 3 months after (2) augmentation. Immu-nohistochemical stains were performed to identify inflammatory cells (T [CD3] and B [CD20] lymphocytes, plasma cells [CD138]), macrophages (CD68-proinflammatory, CD163-anti-inflammatory/ reparative), endothelial cells (CD31, CD34), and fibroblasts (CD90, TE-7). Differences in the mean positively stained cells pre- and postaugmentation were analyzed by Wilcoxon signed-rank test. CD31+ endothelial cells showed increased mean numbers in MM2 compared to MM1 (P = .025) and in LM2 compared to LM1 (P = .047). CD163+ anti-inflammatory macrophages showed higher mean numbers in MM2 than in MM1 (P = .021) and in LM2 than in LM1 (P = .012). All other cell phenotypes showed nonsignificant changes between pre- and postaugmentation. This molecular study provides novel insight on the frequency of stromal cell phenotypes in the wound healing process at 3 months postaugmentation with VCMX, with anti-inflammatory CD163+ macrophages being predominant. This should be further investigated to help find novel therapeutic approaches to modulate and promote the VCMX-related healing process. [ABSTRACT FROM AUTHOR]

Multiple adjacent gingival recessions (MAGRs) are commonly treated with autogenous grafts. However, several intra- and postsurgical complications have been described following autogenous grafts, leading clinicians to explore the use of different biomaterials to treat these conditions. The aim of the present study was to evaluate the root coverage outcomes of a novel porcine-derived acellular dermal matrix (PADM) in combination with the tunneled coronally advanced flap (TCAF) for the treatment of MAGRs. Ten patients with 33 type 1 recession defects (RT1s) were treated with PADM + TCAF. The outcomes of interest included the mean root coverage (mRC), the frequency of complete root coverage (CRC), changes in keratinized tissue width, volumetric gain at the treated sites (assessed with digital intraoral scanning), and patient-reported outcome measures. All treated sites healed uneventfully, and no complications were noted throughout the study. At 6 months, a statistically significant reduction in recession was noted at the treated sites, exhibiting an overall mRC of 89.14% ± 19.15% and a CRC of 72.7%. The average volume gain after 6 months was 26.28 ± 11.71 mm3, and the mean distance between the surface/mean thickness of the reconstructed volume (DD) was 0.63 ± 0.28 mm. The region-specific volumetric analysis revealed an overall higher linear dimensional gain at the midroot aspect (range: 0.72 to 0.78 mm, assessed 1 to 4 mm apical to the cementoenamel junction) compared to the other regions. The present study presents the clinical and volumetric outcomes of PADM + TCAF for the treatment of MAGRs. A significant amount of volumetric gain was also observed at 6 months as a result of the treatment, along with satisfactory esthetic and patient-reported outcomes. [ABSTRACT FROM AUTHOR]

Bacterial nanocellulose (BNC) is a durable, flexible, and dynamic biomaterial capable of serving a wide variety of fields, sectors, and applications within biotechnology, healthcare, electronics, agriculture, fashion, and others. BNC is produced spontaneously in carbohydrate-rich bacterial culture media, forming a cellulosic pellicle via a nanonetwork of fibrils extruded from certain genera. Herein, we demonstrate engineering BNC-based scaffolds with tunable physical and mechanical properties through postprocessing. Human skeletal muscle myoblasts (HSMMs) were cultured on these scaffolds, and in vitro electrical stimulation was applied to promote cellular function for tissue engineering applications. We compared physiologic maturation markers of human skeletal muscle myoblast development using a 2.5-dimensional culture paradigm in fabricated BNC scaffolds, compared to two-dimensional (2D) controls. We demonstrate that the culture of human skeletal muscle myoblasts on BNC scaffolds developed under electrical stimulation produced highly aligned, physiologic morphology of human skeletal muscle myofibers compared to unstimulated BNC and standard 2D culture. Furthermore, we compared an array of metrics to assess the BNC scaffold in a rigorous head-to-head study with commercially available, clinically approved matrices, Kerecis Omega3 Wound Matrix (Marigen) and Phoenix as well as a gelatin methacryloyl (GelMA) hydrogel. The BNC scaffold outcompeted industry standard matrices as well as a 20% GelMA hydrogel in durability and sustained the support of human skeletal muscle myoblasts in vitro. This work offers a robust demonstration of BNC scaffold cytocompatibility with human skeletal muscle cells and sets the basis for future work in healthcare, bioengineering, and medical implant technological development.

Background: Autologous tissues such as buccal mucosa (BM) are widely used for reconstruction of urethral strictures; however, limitations such as donor site morbidity and scarce tissue supply require the development of alternative biomaterials for urethral repair. The goals of this study were to determine the safety and efficacy of bi-layer silk fibroin (BLSF) matrices for urethral stricture repair and compare histological and functional outcomes to the standard approach, BM urethroplasty under good laboratory practices.Material and methods: A total of 13 rabbits exhibiting urethral stricture formation following electrocoagulation injury were treated with onlay urethroplasty with either acellular BLSF (N = 7) or autologous BM (N = 6) grafts for 3 months. Uninjured control rabbits were maintained in parallel (N = 4).Results and conclusion: Animals receiving BLSF implants were demonstrated to be functionally equivalent to BM grafts in their ability to restored strictured calibers, support micturition and promote tissue regeneration with minimal inflammation.

The demand for fish protein continues to increase and currently accounts for 17% of total animal protein consumption by humans. About 90% of marine fish stocks are fished at or above maximum sustainable levels, with aquaculture propagating as one of the fastest growing food sectors to address some of this demand. Cell-cultivated seafood production is an alternative approach to produce nutritionally-complete seafood products to meet the growing demand. This cellular aquaculture approach offers a sustainable, climate resilient and ethical biotechnological approach as an alternative to conventional fishing and fish farming. Additional benefits include reduced antibiotic use and the absence of mercury. Cell-cultivated seafood also provides options for the fortification of fish meat with healthier compositions, such as omega-3 fatty acids and other beneficial nutrients through scaffold, media or cell approaches. This review addresses the biomaterials, production processes, tissue engineering approaches, processing, quality, safety, regulatory, and social aspects of cell-cultivated seafood, encompassing where we are today, as well as the road ahead. The goal is to provide a roadmap for the science and technology required to bring cellular aquaculture forward as a mainstream food source.

Microgravity has been shown to lead to both muscle atrophy and impaired muscle regeneration. The purpose was to study the efficacy of microgravity to model impaired muscle regeneration in an engineered muscle platform and then to demonstrate the feasibility of performing drug screening in this model. Engineered human muscle was launched to the International Space Station National Laboratory, where the effect of microgravity exposure for 7 days was examined by transcriptomics and proteomics approaches. Gene set enrichment analysis of engineered muscle cultured in microgravity, compared to normal gravity conditions, highlighted a metabolic shift toward lipid and fatty acid metabolism, along with increased apoptotic gene expression. The addition of pro-regenerative drugs, insulin-like growth factor-1 (IGF-1) and a 15-hydroxyprostaglandin dehydrogenase inhibitor (15-PGDH-i), partially inhibited the effects of microgravity. In summary, microgravity mimics aspects of impaired myogenesis, and the addition of these drugs could partially inhibit the effects induced by microgravity.

Synthetic Notch (synNotch) receptors are genetically encoded, modular synthetic receptors that enable mammalian cells to detect environmental signals and respond by activating user-prescribed transcriptional programs. Although some materials have been modified to present synNotch ligands with coarse spatial control, applications in tissue engineering generally require extracellular matrix (ECM)-derived scaffolds and/or finer spatial positioning of multiple ligands. Thus, we develop here a suite of materials that activate synNotch receptors for generalizable engineering of material-to-cell signaling. We genetically and chemically fuse functional synNotch ligands to ECM proteins and ECM-derived materials. We also generate tissues with microscale precision over four distinct reporter phenotypes by culturing cells with two orthogonal synNotch programs on surfaces microcontact-printed with two synNotch ligands. Finally, we showcase applications in tissue engineering by co-transdifferentiating fibroblasts into skeletal muscle or endothelial cell precursors in user-defined micropatterns. These technologies provide avenues for spatially controlling cellular phenotypes in mammalian tissues.

Tissue engineering can provide in vitro models for drug testing, disease modeling, and perhaps someday, tissue/organ replacements. For building 3D heart tissue, the alignment of cardiac cells or cardiomyocytes (CMs) is important in generating a synchronously contracting tissue. To that end, researchers have generated several fabrication methods for building heart tissue, but direct comparisons of pros and cons using the same cell source is lacking. Here, we derived cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) and compare the assembly of these cells using three fabrication methods: cardiospheres, muscle rings, and muscle strips. All three protocols successfully generated compacted tissue comprised of hiPSC-derived CMs stable for at least 2 weeks. The percentage of aligned cells was greatest in the muscle strip (55%) and the muscle ring (50%) compared with the relatively unaligned cardiospheres (35%). The iPSC-derived CMs within the muscle strip also exhibited the greatest elongation, with elongation factor at 2.0 compared with 1.5 for the muscle ring and 1.2 for the cardiospheres. This is the first direct comparison of various fabrication techniques using the same cell source.

Osteoarthritis is characterized by enzymatic breakdown of the articular cartilage via the disruption of chondrocyte homeostasis, ultimately resulting in the destruction of the articular surface. Decades of research have highlighted the importance of inflammation in osteoarthritis progression, with inflammatory cytokines shifting resident chondrocytes into a pro-catabolic state. Inflammation can result in poor outcomes for cells implanted for cartilage regeneration. Therefore, a method to promote the growth of new cartilage and protect the implanted cells from the pro-inflammatory cytokines found in the joint space is required. In this study, we fabricate two gel types: polymer network hydrogels composed of chondroitin sulfate and hyaluronic acid, glycosaminoglycans (GAGs) known for their anti-inflammatory and prochondrogenic activity, and interpenetrating networks of GAGs and collagen I. Compared to a collagen-only hydrogel, which does not provide an anti-inflammatory stimulus, chondrocytes in GAG hydrogels result in reduced production of pro-inflammatory cytokines and enzymes as well as preservation of collagen II and aggrecan expression. Overall, GAG-based hydrogels have the potential to promote cartilage regeneration under pro-inflammatory conditions. Further, the data have implications for the use of GAGs to generally support tissue engineering in pro-inflammatory environments.

The current paradigm of medicine is mostly designed to block or prevent pathological events. Once the disease-led tissue damage occurs, the limited endogenous regeneration may lead to depletion or loss of function for cells in the tissues. Cell therapy is rapidly evolving and influencing the field of medicine, where in some instances attempts to address cell loss in the body. Due to their biological function, engineerability, and their responsiveness to stimuli, cells are ideal candidates for therapeutic applications in many cases. Such promise is yet to be fully obtained as delivery of cells that functionally integrate with the desired tissues upon transplantation is still a topic of scientific research and development. Main known impediments for cell therapy include mechanical insults, cell viability, host's immune response, and lack of required nutrients for the transplanted cells. These challenges could be divided into three different steps: 1) Prior to, 2) during the and 3) after the transplantation procedure. In this review, we attempt to briefly summarize published approaches employing biomaterials to mitigate the above technical challenges. Biomaterials are offering an engineerable platform that could be tuned for different classes of cell transplantation to potentially enhance and lengthen the pharmacodynamics of cell therapies.

Cardiovascular organ-on-a-chip (OoC) devices are composed of engineered or native functional tissues that are cultured under controlled microenvironments inside microchips. These systems employ microfabrication and tissue engineering techniques to recapitulate human physiology. This review focuses on human OoC systems to model cardiovascular diseases, to perform drug screening, and to advance personalized medicine. We also address the challenges in the generation of organ chips that can revolutionize the large-scale application of these systems for drug development and personalized therapy.

Tissue engineering strategies show great potential for repairing osteochondral defects in osteoarthritic joints; however, these approaches often rely on passaging cells multiple times to obtain enough cells to produce functional tissue. Unfortunately, monolayer expansion culture causes chondrocyte dedifferentiation, which is accompanied by a phenotypical and morphological shift in chondrocyte properties that leads to a reduction in the quality of de novo cartilage produced. Thus, the objective of this study was to evaluate transcriptional variations during in vitro expansion culture and determine how differences in cell phenotype from monolayer expansion alter development of functional engineered cartilage. We used an unbiased approach to explore genome-wide transcriptional differences in chondrocyte phenotype at passage 1 (P1), P3, and P5, and then seeded cells into hydrogel scaffolds at P3 and P5 to assess cells' abilities to produce cartilaginous extracellular matrix in three dimensional (3D). We identified distinct phenotypic differences, specifically for genes related to extracellular organization and cartilage development. Both P3 and P5 chondrocytes were able to produce chondrogenic tissue in 3D, with P3 cells producing matrix with greater compressive properties and P5 cells secreting matrix with higher glycosaminoglycan/DNA and collagen/DNA ratios. Furthermore, we identified 24 genes that were differentially expressed with passaging and enriched in human osteoarthritis (OA) genome-wide association studies, thereby prioritizing them as functionally relevant targets to improve protocols that recapitulate functional healthy cartilage with cells from adult donors. Specifically, we identified novel genes, such as TMEM190 and RAB11FIP4, which were enriched with human hip OA and may play a role in chondrocyte dedifferentiation. This work lays the foundation for several pathways and genes that could be modulated to enhance the efficacy for chondrocyte culture for tissue regeneration, which could have transformative impacts for cell-based cartilage repair strategies.

Over the past two decades, the Khoury plate technique has been widely utilized with much success to facilitate bone augmentation in critically deficient bone areas. Simply, the technique includes harvesting autogenous bone plates and utilizing them with external screw fixation. The rigidity of the bone plates enclosing the bony defect on both the buccal and lingual surfaces allows for tension-free bone remodeling to occur, favoring an ideal bone-forming environment. Following, a 4- to 6-month healing period, a flap is raised, screws may be removed, and implants are placed. With advancements made in tissue engineering, a novel mineral-organic resorbable bone adhesive (MORBA) formulated from underwater biomimetic marine proteins has recently been utilized for immediate bone-to-bone or bone-to-metal fixation. MORBA is a synthetic, injectable, self-setting, and resorbable load-bearing adhesive biomaterial that exhibits over 300 pounds of fixation strength. The unique adhesive properties of MORBA enable it to immediately stabilize dental implants into host bone. The present article describes a novel modification of the Khoury plate technique that utilizes MORBA as a substitute for screws during bone plate fixation. A step-by-step protocol is described that utilizes this novel biomaterial, favoring a more biologic approach to this conventional technique. This novel modification is surgically easier to conduct and is a more biocompatible option that avoids screw fixation and removal. [ABSTRACT FROM AUTHOR]

Spheroids exhibit enhanced cell-cell interactions that facilitate improved survival and mimic the physiological cellular environment in vivo. Cell spheroids have been successfully used as building blocks for engineered tissues, yet the viability of this approach with skeletal muscle spheroids is poorly understood, particularly when incorporated into three-dimensional (3D) constructs. Bioprinting is a promising strategy to recapitulate the hierarchical organization of native tissue that is fundamental to its function. However, the influence of bioprinting on skeletal muscle cell spheroids and their function are yet to be interrogated. Using C2C12 mouse myoblasts and primary bovine muscle stem cells (MuSCs), we characterized spheroid formation as a function of duration and cell seeding density. We then investigated the potential of skeletal muscle spheroids entrapped in alginate bioink as tissue building blocks for bioprinting myogenic tissue. Both C2C12 and primary bovine MuSCs formed spheroids of similar sizes and remained viable after bioprinting. Spheroids of both cell types fused into larger tissue clusters over time within alginate and exhibited tissue formation comparable to monodisperse cells. Compared to monodisperse cells in alginate gels, C2C12 spheroids exhibited greater MyHC expression after 2 weeks, while cells within bovine MuSC spheroids displayed increased cell spreading. Both monodisperse and MuSC spheroids exhibited increased expression of genes denoting mid- and late-stage myogenic differentiation. Together, these data suggest that skeletal muscle spheroids have the potential for generating myogenic tissue via 3D bioprinting and reveal areas of research that could enhance myogenesis and myogenic differentiation in future studies.

The tumor microenvironment (TME) is a diverse milieu of cells including cancerous and non-cancerous cells such as fibroblasts, pericytes, endothelial cells and immune cells. The intricate cellular interactions within the TME hold a central role in shaping the dynamics of cancer progression, influencing pivotal aspects such as tumor initiation, growth, invasion, response to therapeutic interventions, and the emergence of drug resistance. In immunologically 'cold' tumors, the TME is marked by a scarcity of infiltrating immune cells, limited antigen presentation in the absence of potent immune-stimulating signals, and an abundance of immunosuppressive factors. While strategies targeting the TME as a therapeutic avenue in 'cold' tumors have emerged, there is a pressing need for novel approaches that faithfully replicate the complex cellular and non-cellular interactions in order to develop targeted therapies that can effectively stimulate immune responses and improve therapeutic outcomes in patients. Microfluidic devices offer distinct advantages over traditional in vitro 3D co-culture models and in vivo animal models, as they better recapitulate key characteristics of the TME and allow for precise, controlled insights into the dynamic interplay between various immune, stromal and cancerous cell types at any timepoint. This review aims to underscore the pivotal role of microfluidic systems in advancing our understanding of the TME and presents current microfluidic model systems that aim to dissect tumor-stromal, tumor-immune and immune-stromal cellular interactions in various 'cold' tumors. Understanding the intricacies of the TME in 'cold' tumors is crucial for devising effective targeted therapies to reinvigorate immune responses and overcome the challenges of current immunotherapy approaches.

Over the past two decades Biomedical Engineering has emerged as a major discipline that bridges societal needs of human health care with the development of novel technologies. Every medical institution is now equipped at varying degrees of sophistication with the ability to monitor human health in both non-invasive and invasive modes. The multiple scales at which human physiology can be interrogated provide a profound perspective on health and disease. We are at the nexus of creating avatars (herein defined as an extension of digital twins) of human patho/physiology to serve as paradigms for interrogation and potential intervention. Motivated by the emergence of these new capabilities, the IEEE Engineering in Medicine and Biology Society, the Departments of Biomedical Engineering at Johns Hopkins University and Bioengineering at University of California at San Diego sponsored an interdisciplinary workshop to define the grand challenges that face biomedical engineering and the mechanisms to address these challenges. The Workshop identified five grand challenges with cross-cutting themes and provided a roadmap for new technologies, identified new training needs, and defined the types of interdisciplinary teams needed for addressing these challenges. The themes presented in this paper include: 1) accumedicine through creation of avatars of cells, tissues, organs and whole human; 2) development of smart and responsive devices for human function augmentation; 3) exocortical technologies to understand brain function and treat neuropathologies; 4) the development of approaches to harness the human immune system for health and wellness; and 5) new strategies to engineer genomes and cells.

Dental-derived stem cells (DSCs) are attractive cell sources due to their easy access, superior growth capacity and low immunogenicity. They can respond to multiple extracellular matrix signals, which provide biophysical and biochemical cues to regulate the fate of residing cells. However, the direct transplantation of DSCs suffers from poor proliferation and differentiation toward functional cells and low survival rates due to local inflammation. Recently, elegant advances in the design of novel biomaterials have been made to give promise to the use of biomimetic biomaterials to regulate various cell behaviors, including proliferation, differentiation and migration. Biomaterials could be tailored with multiple functionalities, e.g., stimuli-responsiveness. There is an emerging need to summarize recent advances in engineered biomaterials-mediated delivery and therapy of DSCs and their potential applications. Herein, we outlined the design of biomaterials for supporting DSCs and the host response to the transplantation.

Background: Tissue engineering techniques offer new strategies to understand complex processes in a controlled and reproducible system. In this study, we generated bilayered human tissue substitutes consisting of a cellular connective tissue with a suprajacent epithelium (full-thickness stromal-epithelial substitutes or SESS) and human tissue substitutes with an epithelial layer generated on top of an acellular biomaterial (epithelial substitutes or ESS). Both types of artificial tissues were studied at sequential time periods to analyze the maturation process of the extracellular matrix. Results: Regarding epithelial layer, ESS cells showed active proliferation, positive expression of cytokeratin 5, and low expression of differentiation markers, whereas SESS epithelium showed higher differentiation levels, with a progressive positive expression of cytokeratin 10 and claudin. Stromal cells in SESS tended to accumulate and actively synthetize extracellular matrix components such as collagens and proteoglycans in the stromal area in direct contact with the epithelium (zone 1), whereas these components were very scarce in ESS. Regarding the basement membrane, ESS showed a partially differentiated structure containing fibronectin-1 and perlecan. However, SESS showed higher basement membrane differentiation, with positive expression of fibronectin 1, perlecan, nidogen 1, chondroitin-6-sulfate proteoglycans, agrin, and collagens types IV and VII, although this structure was negative for lumican. Finally, both ESS and SESS proved to be useful tools for studying metabolic pathway regulation, revealing differential activation and upregulation of the transforming growth factor-β pathway in ESS and SESS. Conclusions: These results confirm the relevance of epithelial-stromal interaction for extracellular matrix development and differentiation, especially regarding basement membrane components, and suggest the usefulness of bilayered artificial tissue substitutes to reproduce ex vivo the extracellular matrix maturation and development process of human tissues. Highlights: 1- Artificial bilayered substitutes developed by tissue engineering allow the spatiotemporal study of extracellular matrix maturation and development. 2- Epithelial tissue substitutes generated on the surface of acellular biomaterials display limited differentiation levels, with limited expression of relevant extracellular matrix components. 3- Full-thickness stromal-epithelial substitutes with a cellular stroma showed significantly higher levels of maturation and differentiation, with higher expression of epithelial (cytokeratin 10, claudin) and stromal markers (collagens, proteoglycans). 4- For the formation and development of the basement membrane, an interaction process between the epithelial and the stromal cells is necessary for the synthesis of most fibrillar and non-fibrillar components of this structure. 5- Our results confirm the intrinsic capability of epithelial cells to synthesize extracellular matrix components and the positive inductive effect of paracrine factors released by stromal cells. [ABSTRACT FROM AUTHOR]

Photobiomodulation (PBM) therapy is a continuously growing approach to stimulating healing and reducing inflammation and pain. However, its effects in the fields of regenerative medicine and tissue engineering are still under investigation. Studying PBM effects on the regenerative capacity of zebrafish can allow the application of novel clinical approaches where the impact of PBM will be cross‐linked with the stem‐cell therapeutic approaches. This study was done to establish an in‐vivo experimental setup for studying the effects of laser and ultraviolet therapy on zebrafish caudal‐fin regeneration and vascularization. Thirty zebrafish were randomly and equally allocated into three groups. The caudal‐fins of all zebrafish were amputated under anaesthesia. In the first control group, the caudal‐fin was only monitored until fully regenerated. In the second group, the amputated‐fin was irradiated with ultraviolet. Finally, in the third group, the amputated‐fin was irradiated with laser. Caudal‐fin regeneration and vascularization were assessed at days 0, 3, 6, 9, 12, and 15 in all fish. In terms of regeneration, the results indicated that it is possible to discriminate the regenerative effect of laser with the experimental setup as laser therapy showed a statistically significant difference when compared to control‐group. It was also found that regenerative stimulation of the group that received ultraviolet therapy showed significant difference when compared to the control group. In terms of vascularization, there was a statistically significant difference in all groups of the study, which may suggest that laser as well as ultraviolet have limited effects in terms of improving vascularization. This study presented a novel, simple and inexpensive method for the assessment of PBM effects on zebrafish. Laser and ultraviolet therapy appeared to act as regenerative stimulators for caudal‐fin regeneration of zebrafish. However, laser therapy results were, to some extent, better than ultraviolet therapy. This novel in‐vivo design of the experiment led to more rapid and reproducible results than in‐vitro experiments. [ABSTRACT FROM AUTHOR]

Poly(N‐isopropylacrylamide) (PNIPAM) is a versatile polymer known for its phase transition properties, exhibiting a lower critical solution temperature (LCST) of approximately 32°C. Below this temperature, PNIPAM is hydrophilic, while above it, the polymer becomes hydrophobic, making it ideal for thermosensitive drug delivery systems (DDSs). In tissue engineering, PNIPAM provides a biocompatible, nontoxic and stimuli‐responsive surface for cell culture. Its nontoxic nature ensures safety in medical applications. PNIPAM enhances biosensing diagnostics through its affinity for biomolecules, improving accuracy. Widely used in hydrogels, smart textiles, soft robotics and various medical applications, PNIPAM adapts to environmental changes. Its straightforward synthesis allows for the creation of diverse copolymers and composites, applicable in selective reactions and conjugations with fluorescent tags or chemical modifications. PNIPAM's versatility extends to pH‐responsive alternatives, broadening its application spectrum. Practical examples include phase separation in water treatment and cleaning processes. This discussion explores PNIPAM's biomedical and drug delivery applications, particularly in cancer treatment, photothermal therapy (PTT) and photodynamic therapy (PDT), gene delivery and medical imaging. Additionally, it highlights PNIPAM's noncancerous applications, such as small interfering RNA (siRNA) targeting of oncogenes and detailed imaging of deep and tumour tissues. [ABSTRACT FROM AUTHOR]

"Tissue engineering," is a concept that involves the use of scaffolds, cells, and growth factors/signaling molecules in the field of regenerative medicine. The present study was carried out to evaluate the attachment and depth of penetration of the Gingival Mesenchymal Stem Cells (GMSCs) onto the collagen scaffold preconditioned with Fetal Bovine Serum (FBS), Injectable Platelet Rich Fibrin (i-PRF) and a combination of FBS with i-PRF using histological analysis and environmental scanning electron microscopy (ESEM) respectively. In the present study, commercially available collagen membranes were used as scaffolds and divided into 3 groups where Group I was preconditioned with FBS, Group II was preconditioned with i-PRF, and Group III with a combination of FBS and i-PRF. Scaffolds were then seeded with GMSCs and incubated in a CO2 incubator at 37 0C for 7 days. Both histological and ESEM analysis showed proliferation, attachment, and depth of penetration along with the combination of cell morphological changes in all the three groups. In group I cells showed mild depth of penetration along with a round morphological appearance. In group II the cells showed moderate depth of penetration and rounded morphology. In group III maximum depth of penetration was seen along with the round and spheroidal morphology of cells. The combination of the growth media showed the best effect on cell attachment, depth of penetration, and cell morphology. This is the first report demonstrating the effect of the combination of collagen and i-PRF supports the proliferation of GMSCs. Since FBS alone and i-PRF alone exhibited similar cell proliferation it is recommended that i-PRF could be used in clinical scenarios making it xenofree. [ABSTRACT FROM AUTHOR]

Hydrogels are insoluble three-dimensional polymer networks that are water insoluble but can absorb large amounts of water or biological fluid. They can be prepared using a variety of polymers, including both synthetic and natural ones. Either physical crosslinking, chemical crosslinking, or both are used for the preparation of polymeric hydrogels. Hydrogels made from natural polymers like chitosan, gelatin, alginate, cellulose, and hyaluronic acid are promising biomaterials for applications in tissue engineering, cosmetics, agriculture, wound healing, etc. because of their high biocompatibility and biodegradability. The present work reviews the classification of natural polymer-based hydrogels, properties, cross-linking methods, characterization, and their biomedical applications. [ABSTRACT FROM AUTHOR]

Cardiovascular disease such as myocardial infarction is one of the chief reasons for death universally. An extensive variety of natural and synthetic biodegradable polymers have been studied lately for cardiac tissue engineering applications. Cardiac tissue regeneration is a substitute approach for in situ cellular cardiomyoplasties, which is considered to renovate infarcted myocardium utilizing cells, scaffold, and growth factors. Polymer-based scaffolds including graphene and carbon nanotubes can be employed for heart tissue engineering. In this review, we consider the literature in terms of cardiac tissue engineering and discuss the most recent developments in terms of scaffold-based polymers for cardiac tissue regeneration. [ABSTRACT FROM AUTHOR]

Background: Hair follicles (HFs) are dynamic structures which are readily accessible within the skin that contain various pools of stem cells with broad regenerative potential, such as dermal papilla cells (DPCs), dermal sheath cells, and epithelial HF stem cells. DPCs act as signalling centres for HF regeneration. The current method for isolating human DPCs are inefficient. These methods struggle to obtain freshly isolated original DPCs and do not maintain the characteristics of DPCs effectively. Methods: In this study, two simple but more efficient methods were explored. Force-triggered density gradient sedimentation (FDGS) and cocktail enzyme digestion treatment (CEDT) were used to isolate purified DP spheres from human HFs, obtaining purified freshly isolated original DPCs from DP spheres. The expression profiles of isolated DPCs were tested, and gene expression of DPC-specific markers were analyzed using immunofluorescence staining, RT-qPCR and western blot. Results: The 10% Ficoll PM400 was determined as the optimal concentration for FDGS method. Primary DPCs, DSCs and HFSCs were isolated simultaneously using the FDGS and CEDT method. The expression profiles of fresh DPCs isolated using the FDGS and CEDT methods were similar to those of traditionally isolated DPCs. DP-specific markers were expressed at significantly higher levels in freshly isolated DPCs than in traditionally isolated DPCs. Conclusions: Compared to traditional methods, the presented laboratory protocols were able to isolate fresh DPCs with high efficiency, thereby improving their research potential. [ABSTRACT FROM AUTHOR]

Bone regeneration is a complex biological process that relies on the orchestrated interplay of various cellular and molecular events. Bone tissue engineering is currently the most promising method for treating bone regeneration. However, the immunogenicity, stable and cell quantity of seed cells limited their application. Recently, exosomes, which are small extracellular vesicles released by cells, have been found to effectively address these problems and better induce bone regeneration. Meanwhile, a growing line of research has shown the cargos of exosomes may provide effective therapeutic and biomarker tools for bone repair, including miRNA, lncRNA, and proteins. Moreover, engineered scaffolds loaded with exosomes can offer a cell-free bone repair strategy, addressing immunogenicity concerns and providing a more stable functional performance. Herein, we provide a comprehensive summary of the role played by scaffolds loaded with exosomes in bone regeneration, drawing on a systematic analysis of relevant literature available on PubMed, Scopus, and Google Scholar database. [ABSTRACT FROM AUTHOR]

Engineered liver lobule is highly practical in hepatic disease treatment, while constructing a 3D biomimetic lobule with a heterogeneous architecture on a large scale is challenging. Here, inspired by the natural architectural construction of hepatic lobules, biomimetic hepatic lobules are proposed with coaxially through‐pores for nutrient exchange via microfluidic technology. This multi‐channel microfluidic chip is made by parallelly installing capillaries. Sodium alginate (Alg) is pumped through its central channel, while Ca2+‐loaded gelatin methacrylate (GelMA) solutions encapsulating hepatocytes, mesenchymal stem cells, and endothelia cells are pumped through surrounding channels, respectively. The rapid gelation of Alg and Ca2+ brings about an in situ formation of Alg fiber, with heterogeneous multi‐cell‐laden GelMA microcarriers forming around it. The peeled‐off microcarriers each featured with a coaxially through pore, simulating the cord‐like structure of hepatic lobule and facilitating nutrients exchange. Meanwhile, the spatially anisotropic arrangement of cells highly simulates the hepatic architecture. It is demonstrated that by transplanting these biomimetic microparticles into liver in situ, the failed liver in rat shows increased regeneration and decreased necrosis. These results indicated that the microfluidic multi‐compartmental microcarriers provide a new strategy to engineer 3D artificial livers for clinical translation. [ABSTRACT FROM AUTHOR]

Galactic cosmic radiation (GCR) is one of the most serious risks posed to astronauts during missions to the Moon and Mars. Experimental models capable of recapitulating human physiology are critical to understanding the effects of radiation on human organs and developing radioprotective measures against space travel exposures. The effects of systemic radiation are studied using a multi‐organ‐on‐a‐chip (multi‐OoC) platform containing engineered tissue models of human bone marrow (site of hematopoiesis and acute radiation damage), cardiac muscle (site of chronic radiation damage) and liver (site of metabolism), linked by vascular circulation with an endothelial barrier separating individual tissue chambers from the vascular perfusate. Following protracted neutron radiation, the most damaging radiation component in deep space, a greater deviation of tissue function is observed as compared to the same cumulative dose delivered acutely. Further, by characterizing engineered bone marrow (eBM)‐derived immune cells in circulation, 58 unique genes specific to the effects of protracted neutron dosing are identified, as compared to acutely irradiated and healthy tissues. It propose that this bioengineered platform allows studies of human responses to extended radiation exposure in an "astronaut‐on‐a‐chip" model that can inform measures for mitigating cosmic radiation injury. [ABSTRACT FROM AUTHOR]

AbstractThe biomedical industry has witnessed a transformative evolution with the advent of 3D printing technology. However, inherent limitations, such as the inability to produce dynamic human tissues due to the absence of the temporal dimension, have persisted, resulting in static and inanimate printed products. To address this challenge and enable the creation of dynamic and living constructs, the concept of 4D printing has emerged, marking a paradigm shift in additive manufacturing. In 4D printing, time becomes the fourth dimension, breathing life into previously static creations. This review paper explores the journey from 3D to 4D printing and the pivotal role of time in the additive manufacturing process. Specifically, it highlights the integration of time-dependent responsive materials, focusing on stimuli-responsive hydrogels, as a cornerstone in 4D printing advancements. These materials exhibit a remarkable ability to adapt and respond to various stimuli, encompassing physical, chemical, and biological signals. The review delves into recent publications on the synergy between these stimuli and responsive materials, shedding light on their intricate interactions and potential applications. One of the primary areas of interest lies in medical applications, notably tissue engineering, where 4D printing holds immense promise. The paper explores the utilization of 4D printing in creating biomimetic scaffolds that can dynamically adapt to complex tissue environments. Furthermore, the review discusses the technical considerations and prospects of 4D printing technology, emphasizing its potential to revolutionize the biomedical landscape. The amalgamation of 4D printing and stimuli-responsive materials opens new avenues for personalized medicine, localized drug delivery, and regenerative therapies, bridging the gap between static 3D printing and the dynamic requirements of modern healthcare. The present review offers a complete examination of the evolution, challenges, and prospects of 4D printing in biomedical applications, paving the way for transformative innovations in the field. [ABSTRACT FROM AUTHOR]

Since wound healing is one of the most important medical challenges and common dressings have not been able to manage this challenge well today, efforts have been increased to achieve an advanced dressing. Mesenchymal stem cells and exosomes derived from them have shown high potential in healing and regenerating wounds due to their immunomodulatory, anti-inflammatory, immunosuppressive, and high regenerative capacities. However, challenges such as the short life of these cells, the low durability of these cells in the wound area, and the low stability of exosomes derived from them have resulted in limitations in their use for wound healing. Nowadays, different scaffolds are considered suitable biomaterials for wound healing. These scaffolds are made of natural or synthetic polymers and have shown promising potential for an ideal dressing that does not have the disadvantages of common dressings. One of the strategies that has attracted much attention today is using these scaffolds for seeding and delivering MSCs and their exosomes. This combined strategy has shown a high potential in enhancing the shelf life of cells and increasing the stability of exosomes. In this review, the combination of different scaffolds with different MSCs or their exosomes for wound healing has been comprehensively discussed. [ABSTRACT FROM AUTHOR]

Meniscus injuries are common and while surgical strategies have improved, there is a need for alternative therapeutics to improve long-term outcomes and prevent post-traumatic osteoarthritis. Current research efforts in regenerative therapies and tissue engineering are hindered by a lack of understanding of meniscus cell biology and a poorly defined meniscus cell phenotype. This study utilized bulk RNA-sequencing to identify unique and overlapping transcriptomic profiles in cartilage, inner and outer zone meniscus tissue, and passaged inner and outer zone meniscus cells. The greatest transcriptomic differences were identified when comparing meniscus tissue to passaged monolayer cells (> 4,600 differentially expressed genes (DEGs)) and meniscus tissue to cartilage (> 3,100 DEGs). While zonal differences exist within the meniscus tissue (205 DEGs between inner and outer zone meniscus tissue), meniscus resident cells are more similar to each other than to either cartilage or passaged monolayer meniscus cells. Additionally, we identified and validated LUM, PRRX1, and SNTB1 as potential markers for meniscus tissue and ACTA2, TAGLN, SFRP2, and FSTL1 as novel markers for meniscus cell dedifferentiation. Our data contribute significantly to the current characterization of meniscus cells and provide an important foundation for future work in meniscus cell biology, regenerative medicine, and tissue engineering. [ABSTRACT FROM AUTHOR]

Polymer technology has rapidly advanced across diverse domains, particularly in biomedical applications. Among various polymers, polyurethane (PU) hold great potential in developing biomaterials such as biomedical scaffold and drug delivery. In this study, we have innovatively engineered eco‐friendly polyurethane using lignin, a sustainable bio‐polyol derived from oil palm empty fruit bunches. To enhance the physicochemical properties of the PU, we have incorporated hydroxyapatite (HA) into the composites. The inclusion of HA has led to notable improvements in crucial properties such as density, porosity, and water absorption, making these composites ideal candidates for tissue regeneration scaffolds. Furthermore, to assess their biomedical applicability in drug delivery and cell scaffolding, we have employed the quercetin drug model. The results revealed a sustained kinetic release behavior within the polyurethane/hydroxyapatite (PU/HA) composites, showcasing their potential for controlled drug delivery applications. Moreover, cytotoxicity assays conducted using neuro‐2a cell models demonstrated the non‐cytotoxic nature of both PU and PU/HA composites. This finding holds significant implications for biomedical applications, indicating that these composites offer biocompatible platforms for tissue engineering and regenerative medicine endeavors. The ability of these composites to support cell viability underscores their potential for a wide range of biomedical applications, including neural tissue engineering and drug delivery systems targeting brain diseases. These findings pave the way for the development of innovative and sustainable biomaterials with diverse biomedical applications. Highlights: An eco‐friendly polyurethane has been engineered by harnessing liginin‐derived oil palm empty fruit bunches.Incorporation of hydroxyapaptite enhance the physical properties of polyurethane.Controlled kinetic drug release is one of polyurethane/hydroxyapatite (PU/HA) composites features.The PU/HA composites has low cytotoxicity against neuro‐2a cells. [ABSTRACT FROM AUTHOR]

BACKGROUND: In the co-culture environment of mesenchymal stem cells and macrophages, mesenchymal stem cells can promote the polarization of macrophages into anti-inflammatory macrophages to reduce inflammation, and macrophages can promote the osteogenic differentiation of mesenchymal stem cells. The co-culture of both plays an important role in regulating the immune system and promoting tissue regeneration. OBJECTIVE: To summarize the methods, influencing factors and possible mechanisms of co-culture between mesenchymal stem cells and macrophages, and to provide theoretical basis and experimental methods for the application of co-culture of mesenchymal stem cells and macrophages in tissue engineering. METHODS: The first author searched the relevant articles published from January 1970 to September 2023 in PubMed and CNK by computer from January to September 2023. The Chinese and English key words were “mesenchymal stem cells, macrophages, co-culture”. Finally, 63 articles were included and analyzed. RESULTS AND CONCLUSION: (1) In vitro co-culture of mesenchymal stem cells and macrophages can be divided into direct contact co-culture and indirect contact co-culture according to the model, and two-dimensional cell co-culture and three-dimensional cell co-culture according to the dimension. (2) The coculture of mesenchymal stem cells and macrophages can promote the polarization of macrophages towards M2 type and enhance the osteogenic effect of mesenchymal stem cells. (3) In the co-culture model, the methods of co-culture, the proportion and time of co-culture, the phenotype of macrophages, and the cell source and conditions all affected the immune regulation of macrophages and the osteogenesis of mesenchymal stem cells. (4) Cell interaction in coculture may regulate the immune function of macrophages, proliferation, migration and osteogenesis of mesenchymal stem cells through cell-secreted soluble factors, extracellular vesicles, cell-cell contact, and metabolic pathways. (5) Mesenchymal stem cells and macrophages can enhance cardiac function after acute myocardial infarction, promote epithelial wound healing, reduce lung inflammation, improve renal function, and accelerate bone repair. (6) There are still some problems in co-culture of mesenchymal stem cells and macrophages, such as the selection of co-culture conditions, the maintenance of good cell state and interaction of co-cultured cells. (7) The co-culture of mesenchymal stem cells and macrophages can improve the local inflammatory microenvironment and promote tissue regeneration and repair, so it will have a broad application prospect in tissue engineering. [ABSTRACT FROM AUTHOR]

Trends in health care delivery systems have shifted as a result of the modern uses of biomaterials in medicine. Contrary to traditional medicine, modern healthcare are now useful in solving problems that were considered impossible some years back. One of the most significant factors to the most recent advancements in implant development has been the use of calcium based materials in the creation of necessary implants in the form of soft and hard tissues. With the advent of naturally sourced materials in the manufacturing of biomaterials, lots of attention are now focused on the different sources of agro-based resources that can be used for the product developments. These agro-based materials are now been considered for sustainable and ecological purposes in several areas of applications globally in the recent times. Hence, the review was carried out with focus on the sources, relevance, processing techniques and applications of tricalcium phosphate based biomaterials in modern day healthcare delivery. This review provides a historical and prospective picture of the crucial functions that materials based on tricalcium phosphate will play in fulfilling human requirements for medication. [ABSTRACT FROM AUTHOR]

This article explores the multifaceted potential of pullulan‐based films across food‐packaging, pharmaceutical, biomedical, and cosmetic applications. In food‐packaging, pullulan films serve as transparent, flexible, and high‐oxygen barrier materials, effectively preserving the freshness and quality of a wide range of fruits and vegetables. Edible pullulan films extend the shelf life and enhance food safety, while active pullulan films inhibit microbial growth and oxidation, thus supports food preservation. In the pharmaceutical industry, pullulan‐based films offer promising solutions for oral drug delivery, providing biodegradable and rapid disintegration for enhanced solubility and bioavailability of drugs. Additionally, due to their mechanical strength, biocompatibility, and antimicrobial properties, pullulan films demonstrate potential in wound dressings and tissue engineering applications. Furthermore, pullulan's utility extends to the cosmetic industry, where it is used widely in various ingredients in skincare products, cosmetics, and personal care items. Its moisturizing, stabilizing, and film‐forming properties make pullulan an attractive component in the industry. Future research directions should focus on cost‐effective production methods and expanding industrial applications to further enhance their effectiveness and versatility. This in‐depth analysis highlights the significant potential of pullulan‐based films across multiple industries and underscores the importance of continued research and development efforts to fully unlock their diverse applications and benefits. [ABSTRACT FROM AUTHOR]

Purpose: We sought to engage with expert patient/carers to understand attitudes towards use of tissue engineering (TE) for long-gap oesophageal atresia (OA). Methods: An in-person engagement event for 70 patients/parents was held by the OA patient group, TOFS. Attitudes towards TE were assessed before and after a talk on use of TE oesophagi in a pre-clinical OA model. Perceptions were assessed using a 5-point Likert scale (median [range]) and compared using Mann–Whitney test. Results: 43 attendees responded; 56% parents/caregivers, 21% patients, 7% healthcare workers, 16% unreported. Most (85%) had some awareness of TE but for 15%, it was a new concept. Attendees were receptive to TE; 89% reported no concerns about growth of their/child(s) cells in a lab and 61% reported no concerns about using animal products. Perceptions of TE significantly improved after the presentation from 4 (2–5, n = 32) to 5 (3–5, n = 28) p < 0.0001, and 96% would like to be involved in focus groups on development of a TE product for use in OA. Conclusion: Input from key stakeholders is essential to introduction of TE constructs clinically. The overall response to TE constructs was positive, and informs development of an OA-specific focus group to guide translation. [ABSTRACT FROM AUTHOR]

Background : With over 2 million grafts performed annually, bone ranks second only to blood in the frequency of transplants. This high demand is primarily driven by the persistent challenges posed by bone defects, particularly following trauma or surgical interventions such as tumour excision. The demand for effective and efficient treatments has increased exponentially in the twenty-first century. Limitations associated with autologous bone grafts drive exploration into replacements, including allografts, synthetic substitutes, and 3D-printed scaffolds. This research aimed to unravel disparities in the knowledge and evaluation of current and future bone defect treatments between surgeons and biomaterial scientists. Methods: A prospective cross-sectional survey, pre-registered with the OSF (https://osf.io/y837m/?view%5fonly=fab29e24df4f4adf897353ac70aa3361) and conducted online from October 2022 to March 2023, collected data on surgeons' views (n = 337) and scientists (n = 99) on bone defect treatments. Results: Scientists were significantly more optimistic than surgeons regarding the future replacement of autologous bone grafts with synthetic or tissue-engineered substitutes (p < 0.001). Accordingly, scientists foresee a paradigm shift from autologous bone grafts to biomaterial and tissue-engineered solutions, reflecting their confidence in the ongoing advancements within this field. Furthermore, regulatory trepidations for 3D-printed bone scaffolds were acknowledged, with scientists emphasizing the need for a more significant focus on clinical relevance in preclinical studies and regulatory clarity. In a ranked categorical assessment, witnessing the technology in action was deemed most influential in adopting new bone regeneration methods by both scientists and surgeons. Conclusions: To conclude, this study was conducted through a web-based survey, highlighting a substantial translational gap. It underscores the immediate need ("call to action") for meaningful interdisciplinary collaboration between surgeons and scientists, often referred to as the need to "walk the talk". The findings underscore the critical importance of aligning clinical needs, research outcomes, and regulatory frameworks to improve the development and implementation of biomaterial-based bone graft substitutes that demonstrate efficacy and efficiency in bone defect treatment. [ABSTRACT FROM AUTHOR]

Bladder cancer (BCa) poses a significant health challenge, particularly affecting men with higher incidence and mortality rates. Addressing the need for improved predictive models in BCa treatment, this study introduces an innovative 3D in vitro patient-derived bladder cancer tumor model, utilizing decellularized pig bladders as scaffolds. Traditional 2D cell cultures, insufficient in replicating tumor microenvironments, have driven the development of sophisticated 3D models. The study successfully achieved pig bladder decellularization through multiple cycles of immersion in salt solutions, resulting in notable macroscopic and histological changes. This process confirmed the removal of cellular components while preserving the native extracellular matrix (ECM). Quantitative analysis demonstrated the efficacy of decellularization, with a remarkable reduction in DNA concentration, signifying the removal of over 95% of cellular material. In the development of the in vitro bladder cancer model, muscle invasive bladder cancer patients' cells were cultured within decellularized pig bladders, yielding a three-dimensional cancer model. Optimal results were attained using an air–liquid interface technique, with cells injected directly into the scaffold at three distinct time points. Histological evaluations showcased characteristics resembling in vivo tumors derived from bladder cancer patients' cells. To demonstrate the 3D cancer model's effectiveness as a drug screening platform, the study treated it with Cisplatin (Cis), Gemcitabine (Gem), and a combination of both drugs. Comprehensive cell viability assays and histological analyses illustrated changes in cell survival and proliferation. The model exhibited promising correlations with clinical outcomes, boasting an 83.3% reliability rate in predicting treatment responses. Comparison with traditional 2D cultures and spheroids underscored the 3D model's superiority in reliability, with an 83.3% predictive capacity compared to 50% for spheroids and 33.3% for 2D culture. Acknowledging limitations, such as the absence of immune and stromal components, the study suggests avenues for future improvements. In conclusion, this innovative 3D bladder cancer model, combining decellularization and patient-derived cells, marks a significant advancement in preclinical drug testing. Its potential for predicting treatment outcomes and capturing patient-specific responses opens new avenues for personalized medicine in bladder cancer therapeutics. Future refinements and validations with larger patient cohorts hold promise for revolutionizing BCa research and treatment strategies. [ABSTRACT FROM AUTHOR]

The lack of representative in vitro models recapitulating human tendon (patho)physiology is among the major factors hindering consistent progress in the knowledge‐based development of adequate therapies for tendinopathy.Here, an organotypic 3D tendon‐on‐chip model is designed that allows studying the spatiotemporal dynamics of its cellular and molecular mechanisms.Combining the synergistic effects of a bioactive hydrogel matrix with the biophysical cues of magnetic microfibers directly aligned on the microfluidic chip, it is possible to recreate the anisotropic architecture, cell patterns, and phenotype of tendon intrinsic (core) compartment. When incorporated with vascular‐like vessels emulating the interface between its intrinsic‐extrinsic compartments, crosstalk with endothelial cells are found to drive stromal tenocytes toward a reparative profile. This platform is further used to study adaptive immune cell responses at the onset of tissue inflammation, focusing on interactions between tendon compartment tenocytes and circulating T cells.The proinflammatory signature resulting from this intra/inter‐cellular communication induces the recruitment of T cells into the inflamed core compartment and confirms the involvement of this cellular crosstalk in positive feedback loops leading to the amplification of tendon inflammation.Overall, the developed 3D tendon‐on‐chip provides a powerful new tool enabling mechanistic studies on the pathogenesis of tendinopathy as well as for assessing new therapies. [ABSTRACT FROM AUTHOR]

The rising aging population underscores the need for advances in tissue engineering and regenerative medicine. Alterations in cellular response in microgravity might be pivotal in unraveling the intricate cellular mechanisms governing tissue and organ regeneration. Microgravity could improve multicellular spheroid, tissue, and organ formation. This review summarizes microgravity-induced cellular alterations and highlights the potential of tissue engineering in microgravity for future breakthroughs in space travel, transplantation, drug testing, and personalized medicine. [ABSTRACT FROM AUTHOR]

Extracellular matrix (ECM) viscoelasticity broadly regulates cell behavior. While hydrogels can approximate the viscoelasticity of native ECM, it remains challenging to recapitulate the rapid stress relaxation observed in many tissues without limiting the mechanical stability of the hydrogel. Here, we develop macroporous alginate hydrogels that have an order of magnitude increase in the rate of stress relaxation as compared to bulk hydrogels. The increased rate of stress relaxation occurs across a wide range of polymer molecular weights (MWs), which enables the use of high MW polymer for improved mechanical stability of the hydrogel. The rate of stress relaxation in macroporous hydrogels depends on the volume fraction of pores and the concentration of bovine serum albumin, which is added to the hydrogels to stabilize the macroporous structure during gelation. Relative to cell spheroids encapsulated in bulk hydrogels, spheroids in macroporous hydrogels have a significantly larger area and smaller circularity because of increased cell migration. A computational model provides a framework for the relationship between the macroporous architecture and morphogenesis of encapsulated spheroids that is consistent with experimental observations. Taken together, these findings elucidate the relationship between macroporous hydrogel architecture and stress relaxation and help to inform the design of macroporous hydrogels for materials-based cell therapies. [ABSTRACT FROM AUTHOR]

Collagen is the most abundant protein found in humans and is fundamental to tissue structure and function. Collagen products used in biomedical research are primarily derived from mammals, and despite being mainly responsible for providing strength to native connective tissue, collagen hydrogels have comparatively low mechanical properties without the use of additional cross‐linking strategies. Alternative sources of collagen, like fish collagen, are emerging as key biomaterials in tissue engineering and regenerative medicine (TERM). By addressing cultural/religious concerns, ease of extraction, absence of mammalian‐derived allergens, and retention of functional motifs, fish collagen has many promising characteristics that make it a suitable alternative to mammalian collagen. Several physical and chemical cross‐linking strategies of fish collagen are explored to create more stable and resilient scaffolds for a variety of TERM applications. This comprehensive review explores how these modifications are optimized in fish collagen hydrogel systems. Herein, the use of fish collagen and their reported sources for TERM research, as well as the types of treatments (including sterilization) used to alter collagen structures and functions, are presented to date. [ABSTRACT FROM AUTHOR]

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

Background: Cell therapy has emerged as a revolutionary tool to repair damaged tissues by restoration of an adequate vasculature. Dental Pulp stem cells (DPSC), due to their easy biological access, ex vivo properties, and ability to support angiogenesis have been largely explored in regenerative medicine. Methods: Here, we tested the capability of Dental Pulp Stem Cell-Conditioned medium (DPSC-CM), produced in normoxic (DPSC-CM Normox) or hypoxic (DPSC-CM Hypox) conditions, to support angiogenesis via their soluble factors. CMs were characterized by a secretome protein array, then used for in vivo and in vitro experiments. In in vivo experiments, DPSC-CMs were associated to an Ultimatrix sponge and injected in nude mice. After excision, Ultimatrix were assayed by immunohistochemistry, electron microscopy and flow cytometry, to evaluate the presence of endothelial, stromal, and immune cells. For in vitro procedures, DPSC-CMs were used on human umbilical-vein endothelial cells (HUVECs), to test their effects on cell adhesion, migration, tube formation, and on their capability to recruit human CD14+ monocytes. Results: We found that DPSC-CM Hypox exert stronger pro-angiogenic activities, compared with DPSC-CM Normox, by increasing the frequency of CD31+ endothelial cells, the number of vessels and hemoglobin content in the Ultimatrix sponges. We observed that Utimatrix sponges associated with DPSC-CM Hypox or DPSC-CM Normox shared similar capability to recruit CD45− stromal cells, CD45+ leukocytes, F4/80+ macrophages, CD80+ M1-macrophages and CD206+ M2-macropages. We also observed that DPSC-CM Hypox and DPSC-CM Normox have similar capabilities to support HUVEC adhesion, migration, induction of a pro-angiogenic gene signature and the generation of capillary-like structures, together with the ability to recruit human CD14+ monocytes. Conclusions: Our results provide evidence that DPSCs-CM, produced under hypoxic conditions, can be proposed as a tool able to support angiogenesis via macrophage polarization, suggesting its use to overcome the issues and restrictions associated with the use of staminal cells. [ABSTRACT FROM AUTHOR]

Spatiotemporally controlled two‐photon photodegradation of hydrogels has gained increasing attention for high‐precision subtractive tissue engineering. However, conventional photolabile hydrogels often have poor efficiency upon two‐photon excitation in the near‐infrared (NIR) region and thus require high laser dosage that may compromise cell activity. As a result, high‐speed two‐photon hydrogel erosion in the presence of cells remains challenging. Here we introduce the design and synthesis of efficient coumarin‐based photodegradable hydrogels to overcome these limitations. A set of photolabile coumarin‐functionalized polyethylene glycol linkers are synthesized through a Passerini multicomponent reaction. After mixing these linkers with thiolated hyaluronic acid, semi‐synthetic photodegradable hydrogels are formed in situ via Michael addition crosslinking. The efficiency of photodegradation in these hydrogels is significantly higher than that in nitrobenzyl counterparts upon two‐photon irradiation at 780 nm. A complex microfluidic network mimicking the bone microarchitecture is successfully fabricated in preformed coumarin hydrogels at high speeds of up to 300 mm s−1 and low laser dosage down to 10 mW. Further, we demonstrate fast two‐photon printing of hollow microchannels inside a hydrogel to spatiotemporally direct cell migration in 3D. Collectively, these hydrogels may open new avenues for fast laser‐guided tissue fabrication at high spatial resolution. [ABSTRACT FROM AUTHOR]