An architecturally rational hemostat for rapid stopping of massive bleeding on anticoagulation therapy.

Hemostatic devices are critical for managing emergent severe bleeding. With the increased use of anticoagulant therapy, there is a need for next-generation hemostats. We rationalized that a hemostat with an architecture designed to increase contact with blood, and engineered from a material that activates a distinct and undrugged coagulation pathway can address the emerging need. Inspired by lung alveolar architecture, here, we describe the engineering of a next-generation single-phase chitosan hemostat with a tortuous spherical microporous design that enables rapid blood absorption and concentrated platelets and fibrin microthrombi in localized regions, a phenomenon less observed with other classical hemostats without structural optimization. The interaction between blood components and the porous hemostat was further amplified based on the charged surface of chitosan. Contrary to the dogma that chitosan does not directly affect physiological clotting mechanism, the hemostat induced coagulation via a direct activation of platelet Toll-like receptor 2. Our engineered porous hemostat effectively stopped the bleeding from murine liver wounds, swine liver and carotid artery injuries, and the human radial artery puncture site within a few minutes with significantly reduced blood loss, even under the anticoagulant treatment. The integration of engineering design principles with an understanding of the molecular mechanisms can lead to hemostats with improved functions to address emerging medical needs.

Macrophages modulate stiffness-related foreign body responses through plasma membrane deformation.

Implants are widely used in medical applications and yet macrophage-mediated foreign body reactions caused by implants severely impact their therapeutic effects. Although the extensive use of multiple surface modifications has been introduced to provide some mitigation of fibrosis, little is known about how macrophages recognize the stiffness of the implant and thus influence cell behaviors. Here, we demonstrated that macrophage stiffness sensing leads to differential inflammatory activation, resulting in different degrees of fibrosis. The potential mechanism for macrophage stiffness sensing in the early adhesion stages tends to involve cell membrane deformations on substrates with different stiffnesses. Combining theory and experiments, we show that macrophages exert traction stress on the substrate through adhesion and altered membrane curvature, leading to the uneven distribution of the curvature-sensing protein Baiap2, resulting in cytoskeleton remodeling and inflammation inhibition. This study introduces a physical model feedback mechanism for early cellular stiffness sensing based on cell membrane deformation, offering perspectives for future material design and targeted therapies.

Reversible dougong structured receptor-ligand recognition for building dynamic extracellular matrix mimics.

Dynamic biomaterials excel at recapitulating the reversible interlocking and remoldable structure of the extracellular matrix (ECM), particularly in manipulating cell behaviors and adapting to tissue morphogenesis. While strategies based on dynamic chemistries have been extensively studied for ECM-mimicking dynamic biomaterials, biocompatible molecular means with biogenicity are still rare. Here, we report a nature-derived strategy for fabrication of dynamic biointerface as well as a three-dimensional (3D) hydrogel structure based on reversible receptor-ligand interaction between the glycopeptide antibiotic vancomycin and dipeptide d-Ala-d-Ala. We demonstrate the reversible regulation of multiple cell types with the dynamic biointerface and successfully implement the dynamic hydrogel as a functional antibacterial 3D scaffold to treat tissue repair. In view of the biogenicity and high applicability, this nature-derived reversible molecular strategy will bring opportunities for malleable biomaterial design with great potential in biomedicine.

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

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

A new era of cancer immunotherapy: combining revolutionary technologies for enhanced CAR-M therapy.

Significant advancements have been made in the application of chimeric antigen receptor (CAR)-T treatment for blood cancers during the previous ten years. However, its effectiveness in treating solid tumors is still lacking, necessitating the exploration of alternative immunotherapies that can overcome the significant challenges faced by current CAR-T cells. CAR-based immunotherapy against solid tumors shows promise with the emergence of macrophages, which possess robust phagocytic abilities, antigen-presenting functions, and the ability to modify the tumor microenvironment and stimulate adaptive responses. This paper presents a thorough examination of the latest progress in CAR-M therapy, covering both basic scientific studies and clinical trials. This study examines the primary obstacles hindering the realization of the complete potential of CAR-M therapy, as well as the potential strategies that can be employed to overcome these hurdles. With the emergence of revolutionary technologies like in situ genetic modification, synthetic biology techniques, and biomaterial-supported gene transfer, which provide a wider array of resources for manipulating tumor-associated macrophages, we suggest that combining these advanced methods will result in the creation of a new era of CAR-M therapy that demonstrates improved efficacy, safety, and availability.

Preparation and Application of Hemostatic Hydrogels.

Hemorrhage remains a critical challenge in various medical settings, necessitating the development of advanced hemostatic materials. Hemostatic hydrogels have emerged as promising solutions to address uncontrolled bleeding due to their unique properties, including biocompatibility, tunable physical characteristics, and exceptional hemostatic capabilities. In this review, a comprehensive overview of the preparation and biomedical applications of hemostatic hydrogels is provided. Particularly, hemostatic hydrogels with various materials and forms are introduced. Additionally, the applications of hemostatic hydrogels in trauma management, surgical procedures, wound care, etc. are summarized. Finally, the limitations and future prospects of hemostatic hydrogels are discussed and evaluated. This review aims to highlight the biomedical applications of hydrogels in hemorrhage management and offer insights into the development of clinically relevant hemostatic materials.

Decoding the "Fingerprint" of Implant Materials: Insights into the Foreign Body Reaction.

Foreign body reaction (FBR) is a prevalent yet often overlooked pathological phenomenon, particularly within the field of biomedical implantation. The presence of FBR poses a heavy burden on both the medical and socioeconomic systems. This review seeks to elucidate the protein "fingerprint" of implant materials, which is generated by the physiochemical properties of the implant materials themselves. In this review, the activity of macrophages, the formation of foreign body giant cells (FBGCs), and the development of fibrosis capsules in the context of FBR are introduced. Additionally, the relationship between various implant materials and FBR is elucidated in detail, as is an overview of the existing approaches and technologies employed to alleviate FBR. Finally, the significance of implant components (metallic materials and non-metallic materials), surface CHEMISTRY (charge and wettability), and physical characteristics (topography, roughness, and stiffness) in establishing the protein "fingerprint" of implant materials is also well documented. In conclusion, this review aims to emphasize the importance of FBR on implant materials and provides the current perspectives and approaches in developing implant materials with anti-FBR properties.

Amphipathic Astaxanthin Additive for Low Voltage-loss Perovskite Solar Cells With Enhanced Quasi-Fermi Level Splitting and Solar Hydrogen Production Application.

Even though the power conversion efficiency (PCE) of perovskite solar cells (PSCs) is nearly approaching the Schottky-Queisser limit, low open-circuit voltage (Voc) and severe Voc loss problems continue to impede the improvement of PCEs. Astaxanthin (ASTA) additive is introduced in the formamidinium lead triiodide (FAPbI3) perovskite film as an additive, which can facilitate the transportation of charge carriers and interact with Pb2+ by its distinctive groupings. Furthermore, the addition of ASTA decreases the defect's active energy, regulates the deep-level defect by filling up the grain boundaries (GBs), and promotes the crystallization of perovskite film. Remarkably, an enhanced quasi-Fermi level splitting (QFLS) of 1.164 eV and a reduced Voc loss of only 96 mV are realized. The champion PCE of 24.56% is attained by ASTA-modified PSCs on the basis of 22.75% PCE. Moreover, the PSCs that underwent ASTA modification demonstrate improved operational stability, ensuring consistent output in real-world scenarios. Furthermore, PSCs with an active area of 1 cm2 are used for water electrolysis to produce hydrogen and exhibit a PCE of 22.41%. This work offers an environmentally benign solution to address the inherent issues of FAPbI3 PSCs and lays the groundwork for the development of a prospective solar hydrogen production application.

Super-Strong, Super-Stiff, and Super-Tough Fluorescent Alginate Fibers with Outstanding Tolerance to Extreme Conditions.

The combination of multiple physical properties is of great importance for widening the application scenarios of biomaterials. It remains a great challenge to fabricate biomolecules-based fibers gaining both mechanical strength and toughness which are comparable to natural spider dragline silks. Here, by mimicking the structure of dragline silks, a high-performance fluorescent fiber Alg-TPEA-PEG is designed by non-covalently cross-linking the polysaccharide chains of alginate with AIEgen-based surfactant molecules as the flexible contact points. The non-covalent cross-linking network provides sufficient energy-dissipating slippage between polysaccharide chains, leading to Alg-TPEA-PEG with highly improved mechanical performances from the plastic strain stage. By successfully transferring the extraordinary mechanical performances of polysaccharide chains to macroscopic fibers, Alg-TPEA-PEG exhibits an outstanding breaking strength of 1.27 GPa, Young's modulus of 34.13 GPa, and toughness of 150.48 MJ m-3, which are comparable to those of dragline silk and outperforming other artificial materials. More importantly, both fluorescent and mechanical properties of Alg-TPEA-PEG can be well preserved under various harsh conditions, and the fluorescence and biocompatibility facilitate its biological and biomedical applications. This study affords a new biomimetic designing strategy for gaining super-strong, super-stiff, and super-tough fluorescent biomaterials.

Strategies and Applications for Supramolecular Protein Self-Assembly.

Supramolecular chemistry achieves higher-order molecular self-assembly through non-covalent interactions. Utilizing supramolecular methods to explore the polymorphism of proteins, the building blocks of life, from a "bottom-up" perspective is essential for constructing diverse and functional biomaterials. In recent years, significant progress has been achieved in the design strategies and functional applications of supramolecular protein self-assembly, becoming a focal point for researchers. This paper reviews classical supramolecular strategies driving protein self-assembly, including electrostatic interactions, metal coordination, hydrogen bonding, hydrophobic interactions, host-guest interactions, and other mechanisms. We discuss how these supramolecular interactions regulate protein assembly processes and highlight protein supramolecular assemblies' unique structural and functional advantages in constructing artificial photosynthetic systems, protein hydrogels, bio-delivery systems, and other functional materials. The enormous potential and significance of supramolecular protein materials are elucidated. Finally, the challenges in preparing and applying protein supramolecular assemblies are summarized, and future development directions are projected.

Age-related changes on physicochemical properties of the artificial vitreous humor: A practical tool for enhancing ex vivo studies.

The vitreous humor (VH) is a hydrophilic, jelly-like ocular fluid, which is located in the posterior chamber of the eye. The rheological, structural, and chemical properties of VH change significantly during aging, which further causes eye-associated diseases and could be a potential indicator for various diseases. In this study, artificial VH (A-VH) samples were created by taking into account different age groups to observe age-related changes in the physicochemical properties of these samples. This study aimed to measure the physicochemical properties of age-dependently prepared A-VH samples to determine the changes with aging in the physicochemical properties of A-VH samples. Phosphate-buffered saline (PBS)-based A-VH samples were prepared in three types representing adult, middle-aged, and elder individuals. Age-related changes in physicochemical properties (surface tension, osmolality, pH, relative viscosity, density, and refractive index) were analyzed by related equipment. The A-VH samples, prepared using PBS, showed strong similarity to authentic VH in terms of physicochemical properties. While the age-related changes studies have revealed some discrepancies between age-dependently prepared A-VH samples in terms of surface tension, osmolality, relative viscosity, and pH with high correlation coefficients (r2 > 0,94), density and refractive index values did not show any significant differences and correlation between types of A-VH representing 3 age groups. In conclusion, age-dependent A-VH samples were created successfully to use ex vivo method development studies, and the influence of aging on the physicochemical properties of VH was demonstrated as well.

3D Printable Alginate-Chitosan Hydrogel Loaded With Ketoconazole Exhibits Anticryptococcal Activity.

Natural polymers have recently been investigated for various applications, such as 3D printing and healthcare, including treating infections. Among microbial infections, fungal diseases remain overlooked, with limited therapeutic options and high recurrence. Cutaneous cryptococcosis is an opportunistic fungal infection triggered by mechanical inoculation or hematogenous dissemination of the yeast that causes cryptococcal pneumonia and meningitis. Every year, Cryptococcus neoformans endanger the lives of immunosuppressed hosts, resulting in 180,000 deaths per year. Nonetheless, healthy individuals can also be affected by this fungal infection. Cryptococcosis has a restricted and expensive therapeutic regimen with no topical approach to skin manifestations. This study sought to create a 3D printable biodegradable polymeric hydrogel carrying ketoconazole, a low-cost antifungal drug with reported anticryptococcal activity. The developed hydrogel exhibited good 3D printability and rheological properties, including a pseudoplastic behavior. The FTIR spectra of cross-linked hydrogels revealed interactions between alginate and Ca+2, referred to as the egg-box model, indicated by the decrease in peaks at 1600 and 1410 cm-1. Furthermore, the hydrogel loaded with ketoconazole showed remarkable antifungal activity against C. neoformans strains indicated by inhibition zones, which cross-linking did not seem to affect its antifungal performance. The developed material remained structurally stable for up to 12 days (288 h) in swelling studies, and preliminary cytotoxicity performed with V79 cells indicates potential for in vivo studies and topical application.

Impact and torsional behavior of additive layer-manufactured biopolymer: An advancement for orthopedic applications.

Distal ulna locking bone plates (DLBPs) are commonly employed in the treatment of distal ulna fractures. However, commercially available metallic bone plates experience stress shielding and lack corrosion resistance. Poly lactic acid (PLA) is highly favored biopolymer due to its biocompatible and bioabsorbable nature with human tissues. The use of additive layer manufacturing (ALM) is gaining attention for creating customized implants with intricate structures tailored to patient autonomy. ALM-based PLA bone plates must provide high resistance against impact and torsional forces, necessitating the adjustment of printing process parameters. This study focuses on examining the influence of key printing parameters, on the impact strength and torque-withstanding capability of DLBPs. Experimental results, along with microscopic images, reveal that an increase in infill density (IF) and wall thickness imparts strong resistance to layers against crack propagation under impact and torsional loads. On the contrary, an increase in layer height and printing speed leads to delamination and early fracture of layers during impact and torsional testing. IF significantly contributes to improving the impact strength and torque-withstanding capability of DLBPs by 70.53% and 80.65%, respectively. The study highlights the potential of the ALM technique in developing DLBPs with sufficient mechanical strength for biomedical applications.

Development of HEMA-Succinic Acid-PEG Bio-Based Monomers for High-Performance Hydrogels in Regenerative Medicine.

In recent years, hydrogels have found a special place in regenerative medicine for tissue repair, rehabilitation, and drug delivery. To be used in regenerative medicine, hydrogels must have desirable physical, chemical, and biological properties. In this study, a new biomonomer based on hydroxyethyl methacrylate-succinic acid-polyethylene glycol 200 (HEMA-Suc-PEG) was synthesized and characterized. Then, using the synthesized monomers and different ratios of polyethylene glycol diacrylate (PEGDA) as a crosslinker, biocompatible hydrogels were synthesized through thermal and UV curing methods. The mechanical, physical, chemical, and biological properties of the hydrogels and the behavior of endothelial cells, an essential component of the cardiovascular system, were evaluated. The results showed that the hydrogel synthesized with 0.2 g of PEGDA (UV curing) has desirable mechanical and physical properties. Biological tests showed that these hydrogels are not only nontoxic to cells but also enhance cell adhesion. Therefore, the hydrogel containing the synthesized monomer HEMA-Suc-PEG and 0.2 g of PEGDA has the potential to be used in the cardiovascular system.

Boolean Logic Gate Operation in Bacteriorhodopsin of Purple Membrane Based on a Molten Globule-like State.

Bacteriorhodopsin (bR) of purple membrane (PM) has increasing technical interests, particularly in photonic devices and bioelectronics. The present work has concerned with monitoring the temperature dependence of passive electric responses in-plane and out-of-plane of the membranes. Based on thermal properties observed orthogonally here for PM, a high-temperature intermediate of bR has been suggested to populate at around 60 °C, which may be ascribed to a molten globule-like state. This intermediate has been found to be enclosed between two reversible thermal transitions for PM. Large-scale turnover in the energy of activation, for these two thermal transitions, occurs steeply at such state at 60 °C, above which does bR reverse the sign of dielectric anisotropy (i. e. crossover) provided the operating frequency should be above the crossover frequency, at which the reversal occurs. No such crossover was found to occur below the crossover frequency, even above the crossover temperature (i. e. 60 °C). Likewise, no such crossover was found to occur below the crossover temperature, even above the crossover frequency. Relying on this reasoning, a logic gate operation may be declared implicating bR for bioelectronics and sense technological relevance. In addition, the results specify "dual frequency" as well as "dual temperature" characteristics to bacteriorhodopsin.

Plants as a cost-effective source for customizable photosynthetic wound dressings: A proof of concept study.

Oxygen is essential for tissue regeneration, playing a crucial role in several processes, including cell metabolism and immune response. Therefore, the delivery of oxygen to wounds is an active field of research, and recent studies have highlighted the potential use of photosynthetic biomaterials as alternative oxygenation approach. However, while plants have traditionally been used to enhance tissue regeneration, their potential to produce and deliver local oxygen to wounds has not yet been explored. Hence, in this work we studied the oxygen-releasing capacity of Marchantia polymorpha explants, showing their capacity to release oxygen under different illumination settings and temperatures. Moreover, co-culture experiments revealed that the presence of these explants had no adverse effects on the viability and morphology of fibroblasts in vitro, nor on the viability of zebrafish larvae in vivo. Furthermore, oxygraphy assays demonstrate that these explants could fulfill the oxygen metabolic requirements of zebrafish larvae and freshly isolated skin biopsies ex vivo. Finally, the biocompatibility of explants was confirmed through a human skin irritation test conducted in healthy volunteers following the ISO-10993-10-2010. This proof-of-concept study provides valuable scientific insights, proposing the potential use of freshly isolated plants as biocompatible low-cost oxygen delivery systems for wound healing and tissue regeneration.

Filamentous fungal pellets as versatile platforms for cell immobilization: developments to date and future perspectives.

Filamentous fungi are well-known for their efficiency in producing valuable molecules of industrial significance, but applications of fungal biomass remain relatively less explored despite its abundant and diverse opportunities in biotechnology. One promising application of mycelial biomass is as a platform to immobilize different cell types such as animal, plant, and microbial cells. Filamentous fungal biomass with little to no treatment is a sustainable biomaterial which can also be food safe compared to other immobilization supports which may otherwise be synthetic or heavily processed. Because of these features, the fungal-cell combination can be tailored towards the targeted application and be applied in a variety of fields from bioremediation to biomedicine. Optimization efforts to improve cell loading on the mycelium has led to advancements both in the applied and basic sciences to understand the inter- and intra-kingdom interactions. This comprehensive review compiles for the first time the current state of the art of the immobilization of animal, yeast, microalgae, bacteria, and plant cells in filamentous fungal supports and presents outlook of applications in intensified fermentations, food and biofuel production, and wastewater treatment. Opportunities for further research and development were identified to include elucidation of the physical, chemical, and biological bases of the immobilization mechanisms and co-culture dynamics; expansion of the cell-fungus combinations investigated; exploration of previously unconsidered applications; and demonstration of scaled-up operations. It is concluded that the potential exists to leverage the unique qualities of filamentous fungus as a cellular support in the creation of novel materials and products in support of the circular bioeconomy.

Effects of a bioengineered allogeneic cellular construct on burn-related macrophage phenotype.

Bioengineered allogeneic cellularised constructs (BACC) exert pro-healing effects in burn wounds and skew macrophage phenotype towards a predominately reparative phenotype. However, whether BACC can modulate the phenotype of dysregulated macrophages, like those present in burn wounds, is not known. To better understand the macrophage modulatory characteristics of the BACC, primary human macrophages were polarised to the M2b phenotype, an immunosuppressive phenotype relevant to burn wounds, by simultaneously exposing macrophages to polystyrene plate-coated immunoglobulin G and the endotoxin lipopolysaccharide (LPS). The resulting macrophage phenotype upregulated both inflammatory and reparative genes, and increased secretion of the M2b marker CCL1 compared to five different in vitro macrophage phenotypes. M2b macrophages were cultured with the BACC in the presence or absence of LPS to mimic infection, which is a common occurrence in burn wounds. The BACC caused up-regulation of reparative gene sets and down-regulation of pro-inflammatory gene sets, even when LPS was present in the cell culture media. Co-cultures were maintained for 1, 3, or 5 days in the presence of LPS, and by day 1 both non-activated macrophages and M2b macrophages exhibited signs of endotoxin tolerance, as demonstrated by a reduced secretion of tumour necrosis factor α (TNFα) in response to fresh LPS stimulus. The BACC was not able to prevent endotoxin tolerance, but reparative genes were upregulated in macrophages chronically exposed to LPS. These results suggest that the BACC can promote a reparative phenotype in dysregulated macrophages relevant to the pathophysiology of burns.

Assessment of human embryonic stem cells differentiation into definitive endoderm lineage on the soft substrates.

Pluripotent stem cells (PSCs) hold enormous potential for treating multiple diseases owing to their ability to self-renew and differentiate into any cell type. Albeit possessing such promising potential, controlling their differentiation into a desired cell type continues to be a challenge. Recent studies suggest that PSCs respond to different substrate stiffness and, therefore, can differentiate towards some lineages via Hippo pathway. Human PSCs can also differentiate and self-organize into functional cells, such as organoids. Traditionally, human PSCs are differentiated on stiff plastic or glass plates towards definitive endoderm and then into functional pancreatic progenitor cells in the presence of soluble growth factors. Thus, whether stiffness plays any role in differentiation towards definitive endoderm from human pluripotent stem cells (hPSCs) remains unclear. Our study found that the directed differentiation of human embryonic stem cells towards endodermal lineage on the varying stiffness did not differ from the differentiation on stiff plastic dishes. We also observed no statistical difference between the expression of yes-associated protein (YAP) and phosphorylated YAP. Furthermore, we demonstrate that lysophosphatidic acid, a YAP activator, enhanced definitive endoderm formation, whereas verteporfin, a YAP inhibitor, did not have the significant effect on the differentiation. In summary, our results suggest that human embryonic stem cells may not differentiate in response to changes in stiffness, and that such cues may not have as significant impact on the level of YAP. Our findings indicate that more research is needed to understand the direct relationship between biophysical forces and hPSCs differentiation.

3D bio scaffold support osteogenic differentiation of mesenchymal stem cells.

The regeneration of osteochondral lesions by tissue engineering techniques is challenging due to the lack of physicochemical characteristics and dual-lineage (osteogenesis and chondrogenesis). A scaffold with better mechanical properties and dual lineage capability is required for the regeneration of osteochondral defects. In this study, a hydrogel prepared from decellularized human umbilical cord tissue was developed and evaluated for osteochondral regeneration. Mesenchymal stem cells (MSCs) isolated from the umbilical cord were seeded with hydrogel for 28 days, and cell-hydrogel composites were cultured in basal and osteogenic media. Alizarin red staining, quantitative polymerase chain reaction, and immunofluorescent staining were used to confirm that the hydrogel was biocompatible and capable of inducing osteogenic differentiation in umbilical cord-derived MSCs. The findings demonstrate that human MSCs differentiated into an osteogenic lineage following 28 days of cultivation in basal and osteoinductive media. The expression was higher in the cell-hydrogel composites cultured in osteoinductive media, as evidenced by increased levels of messenger RNA and protein expression of osteogenic markers as compared to basal media cultured cell-hydrogel composites. Additionally, calcium deposits were also observed, which provide additional evidence of osteogenic differentiation. The findings demonstrate that the hydrogel is biocompatible with MSCs and possesses osteoinductive capability in vitro. It may be potentially useful for osteochondral regeneration.