PHA-665752's Antigrowth and Proapoptotic Effects on HSC-3 Human Oral Cancer Cells.

c-Met is a tyrosine-kinase receptor, and its aberrant activation plays critical roles in tumorigenesis, invasion, and metastatic spread in many human tumors. PHA-665752 (PHA) is an inhibitor of c-Met and has antitumor effects on many hematological malignancies and solid cancers. However, the activation and expression of c-Met and its role and the antitumor effect of PHA on human oral squamous cell carcinoma (OSCC) cells remain unclear. Here, we investigated the activation and expression of c-Met and the effects of PHA on the growth of a highly tumorigenic HSC-3 human OSCC cell line with high c-Met phosphorylation and expression. Of note, c-Met was highly expressed and phosphorylated on Y1234/1235 in HSC-3 cells, and PHA treatment significantly suppressed the growth and induced apoptosis of these cells. Moreover, PHA that inhibited the phosphorylation (activation) of c-Met further caused the reduced phosphorylation and expression levels of Src, protein kinase B (PKB), mammalian target of rapamycin (mTtor), and myeloid cell leukemia-1 (Mcl-1) in HSC-3 cells. In addition, the antiangiogenic property of PHA in HSC-3 cells was shown, as evidenced by the drug's suppressive effect on the expression of hypoxia-inducible factor-1α (HIF-1α), a critical tumor angiogenic transcription factor. Importantly, genetic ablation of c-Met caused the reduced growth of HSC-3 cells and decreased Src phosphorylation and HIF-1α expression. Together, these results demonstrate that c-Met is highly activated in HSC-3 human oral cancer cells, and PHA exhibits strong antigrowth, proapoptotic, and antiangiogenic effects on these cells, which are mediated through regulation of the phosphorylation and expression of multiple targets, including c-Met, Src, PKB, mTOR, Mcl-1, and HIF-1α.

Risk of complications in panfacial bone fracture according to surgeons: A meta-analysis.

BACKGROUND: Panfacial bone fractures pose intricate challenges because of severe fragmentation and the loss of landmarks. Surgeons use a variety of reduction techniques, including bottom-up and top-down approaches. This single proportional meta-analysis explores sequencing differences and complications between oral and maxillofacial surgery surgeons (OMSs) and plastic and reconstructive surgeons (PRSs) in treating panfacial bone fractures. METHODS: The PubMed and Scopus databases were searched systematically, and we compiled 14 studies published between 2007 and 2023 involving 1238 patients. A systematic review of the included studies was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and data on the reduction techniques; total complication rates; and rates of malocclusion, enophthalmos, infection, asymmetry, and esthetic complications were collected. RESULTS: The bottom-up technique was the most prevalent for both types of surgeons (57.1%, 8 out of 14). Malocclusion rates (I2 = 0% for OMSs and 41% for PRSs) were similar between the groups (p = 0.72), but PRSs tended to have a lower enophthalmos rate (I2 = 0% for OMSs and 32% for PRSs) than OMSs (p < 0.01). Infection rates remained consistent across all studies. However, high heterogeneity was observed for the total complication rate (I2 = 94% for OMSs and 85% for PRSs) and asymmetry and esthetic complications (I2 = 88% for OMSs and 92% for PRSs), making direct comparison between the two groups inconclusive. CONCLUSIONS: In this study, the differences in surgical techniques and levels of interest have a greater impact on the outcomes of the panfacial bone fracture than the surgeon's specialty. However, more in-depth studies are needed to accurately pinpoint panfacial bone fracture reduction trends and differences in postoperative complications in the two expert groups.

Engineering of Cell Derived-Nanovesicle as an Alternative to Exosome Therapy.

BACKGROUND: Exosomes, nano-sized vesicles ranging between 30 and 150 nm secreted by human cells, play a pivotal role in long-range intercellular communication and have attracted significant attention in the field of regenerative medicine. Nevertheless, their limited productivity and cost-effectiveness pose challenges for clinical applications. These issues have recently been addressed by cell-derived nanovesicles (CDNs), which are physically synthesized exosome-mimetic nanovesicles from parent cells, as a promising alternative to exosomes. CDNs exhibit structural, physical, and biological properties similar to exosomes, containing intracellular protein and genetic components encapsulated by the cell plasma membrane. These characteristics allow CDNs to be used as regenerative medicine and therapeutics on their own, or as a drug delivery system. METHODS: The paper reviews diverse methods for CDN synthesis, current analysis techniques, and presents engineering strategies to improve lesion targeting efficiency and/or therapeutic efficacy. RESULTS: CDNs, with their properties similar to those of exosomes, offer a cost-effective and highly productive alternative due to their non-living biomaterial nature, nano-size, and readiness for use, allowing them to overcome several limitations of conventional cell therapy methods. CONCLUSION: Ongoing research and enhancement of CDNs engineering, along with comprehensive safety assessments and stability analysis, exhibit vast potential to advance regenerative medicine by enabling the development of efficient therapeutic interventions.

O2 variant chip to simulate site-specific skeletogenesis from hypoxic bone marrow.

The stemness of bone marrow mesenchymal stem cells (BMSCs) is maintained by hypoxia. The oxygen level increases from vessel-free cartilage to hypoxic bone marrow and, furthermore, to vascularized bone, which might direct the chondrogenesis to osteogenesis and regenerate the skeletal system. Hence, oxygen was diffused from relatively low to high levels throughout a three-dimensional chip. When we cultured BMSCs in the chip and implanted them into the rabbit defect models of low-oxygen cartilage and high-oxygen calvaria bone, (i) the low oxygen level (base) promoted stemness and chondrogenesis of BMSCs with robust antioxidative potential; (ii) the middle level (two times ≥ low) pushed BMSCs to quiescence; and (iii) the high level (four times ≥ low) promoted osteogenesis by disturbing the redox balance and stemness. Last, endochondral or intramembranous osteogenesis upon transition from low to high oxygen in vivo suggests a developmental mechanism-driven solution to promote chondrogenesis to osteogenesis in the skeletal system by regulating the oxygen environment.

Taxonomic Review of the Genus Caloptilia Hübner, 1825 (Lepidoptera: Gracillariidae) with Descriptions of Three New Species and Seven Newly Recorded Species from Korea.

In this study, 29 species of Caloptilia Hübner, 1825, belonging to the family Gracillariidae, were recognized in Korea. Among these, three species, i.e., C. purpureus sp. nov., C. koreana sp. nov., and C. xanthos sp. nov., are described as new to science. In addition, seven species of this genus are reported for the first time in Korea. All known species were enumerated, based on their available information. Adult specimens and genitalia of the new and newly recorded species were examined and described using all available information.

Recurrence of Uncomplicated Diverticulitis: A Meta-Analysis.

Background and objective: This study aimed to investigate the estimated rate and risk of recurrence of uncomplicated diverticulitis (UCD) after the first episode through a meta-analysis. Methods: Eligible studies were searched and reviewed; 27 studies were included in this study. Subgroup analyses were performed, based on lesion location, medical treatment, follow-up period, and study location. Results: The estimated recurrence rate of UCD was 0.129 (95% confidence interval [CI] 0.102-0.162). The recurrence rates of the right-and left-sided colon were 0.092 (95% CI 27.063-0.133) and 0.153 (95% CI 0.104-0.218), respectively. The recurrence rate according to follow-up period was highest in the subgroup 1-2 years, compared with that of other subgroups. The recurrence rate of the Asian subgroup was significantly lower than that of the non-Asian subgroup (0.092, 95% CI 0.064-0.132 vs. 0.147, 95% CI 0.110-0.192; p = 0.043 in the meta-regression test). There were significant correlations between UCD recurrence and older age and higher body temperature. However, UCD recurrence was not significantly correlated with medications, such as antibiotics or anti-inflammatory drugs. Conclusions: In this study, detailed information on estimated recurrence rates of UCD was obtained. In addition, older age and higher body temperature may be risk factors for UCD recurrence after the first episode.

Sprayable nanomicelle hydrogels and inflammatory bowel disease patient cell chips for development of intestinal lesion-specific therapy.

All-in-one treatments represent a paradigm shift in future medicine. For example, inflammatory bowel disease (IBD) is mainly diagnosed by endoscopy, which could be applied for not only on-site monitoring but also the intestinal lesion-targeted spray of injectable hydrogels. Furthermore, molecular conjugation to the hydrogels would program both lesion-specific adhesion and drug-free therapy. This study validated this concept of all-in-one treatment by first utilizing a well-known injectable hydrogel that underwent efficient solution-to-gel transition and nanomicelle formation as a translatable component. These properties enabled spraying of the hydrogel onto the intestinal walls during endoscopy. Next, peptide conjugation to the hydrogel guided endoscopic monitoring of IBD progress upon adhesive gelation with subsequent moisturization of inflammatory lesions, specifically by nanomicelles. The peptide was designed to mimic the major component that mediates intestinal interaction with Bacillus subtilis flagellin during IBD initiation. Hence, the peptide-guided efficient adhesion of the hydrogel nanomicelles onto Toll-like receptor 5 (TLR5) as the main target of flagellin binding and Notch-1. The peptide binding potently suppressed inflammatory signaling without drug loading, where TLR5 and Notch-1 operated collaboratively through downstream actions of tumor necrosis factor-alpha. The results were produced using a human colorectal cell line, clinical IBD patient cells, gut-on-a-chip, a mouse IBD model, and pig experiments to validate the translational utility.

Global Nepticulidae, Opostegidae, and Tischeriidae (Lepidoptera): temporal dynamics of species descriptions and their authors.

This study identifies the number of named and described species of three monotrysian, plant-mining lepidopteran families worldwide: Nepticulidae and Opostegidae (Nepticuloidea), and Tischeriidae (Tischerioidea). At the end of 2021, we estimated that a total of 1000 Nepticulidae species, 197 Opostegidae species, and 170 Tischeriidae species have been described since the taxonomic practice of describing species began in the 18th century. We examine and discuss the history of descriptions and authorship of species worldwide for each of the three families. We found that the total (accumulative) number of species described increased with each time period delineated. About five new species were described per year on average, or about 22 new species were described per year in the 21st century. We recognize researchers with the most number of described species in these three taxa.

Quenching Epigenetic Drug Resistance Using Antihypoxic Microparticles in Glioblastoma Patient-Derived Chips.

Glioblastoma (GBM) is one of the most intractable tumor types due to the progressive drug resistance upon tumor mass expansion. Incremental hypoxia inside the growing tumor mass drives epigenetic drug resistance by activating nongenetic repair of antiapoptotic DNA, which could be impaired by drug treatment. Hence, rescuing intertumor hypoxia by oxygen-generating microparticles may promote susceptibility to antitumor drugs. Moreover, a tumor-on-a-chip model enables user-specified alternation of clinic-derived samples. This study utilizes patient-derived glioblastoma tissue to generate cell spheroids with size variations in a 3D microchannel network chip (GBM chip). As the spheroid size increases, epigenetic drug resistance is promoted with inward hypoxia severance, as supported by the spheroid size-proportional expression of hypoxia-inducible factor-1a in the chip. Loading antihypoxia microparticles onto the spheroid surface significantly reduces drug resistance by silencing the expression of critical epigenetic factor, resulting in significantly decreased cell invasiveness. The results are confirmed in vitro using cell line and patient samples in the chip as well as chip implantation into a hypoxic hindlimb ischemia model in mice, which is an unprecedented approach in the field.

Management of Chronic Idiopathic Pain in Patients With Dental Implant Without a Clear Pathological Lesion: A Retrospective Study.

Non-nociceptive, persistent idiopathic facial pain (PIFP) is a poorly localized, continuous dull pain that occurs even in the absence of apparent pathological lesions or clinical neurologic deficiency. This study aimed to investigate the disease characteristics of PIFP that developed after dental implant treatment. The clinical characteristics of pain as well as treatment method and outcomes were retrospectively analyzed in 20 patients diagnosed with PIFP. The patients developed pain either after implant fixation or prosthetic treatment. In most patients, the pain persisted not only around the implant region but also at a distant site from the related implant (13/20, 65%). Many patients desired removal of the implants to manage the pain although the pain was not considered to be related to the implant treatment. In 12 patients, the related implants were removed, but 67% (n = 8/12) of the patients still experienced chronic pain after implant removal. Medication helped decrease the pain in most patients (n = 17). Pregabalin and clonazepam showed relatively higher efficiency than other medications for controlling the pain. The results showed that although the onset of PIFP was related to dental implant treatment, implant removal could not be considered a reliable option for the management of PIFP. Although medication controls the pain at least partially, complete pain control with medication should not be expected. These results demonstrate that an accurate diagnosis of PIFP is important for the selection of appropriate treatment.

Cell-Membrane-Derived Nanoparticles with Notch-1 Suppressor Delivery Promote Hypoxic Cell-Cell Packing and Inhibit Angiogenesis Acting as a Two-Edged Sword.

Cell-cell interactions regulate intracellular signaling via reciprocal contacts of cell membranes in tissue regeneration and cancer growth, indicating a critical need of membrane-derived tools in studying these processes. Hence, cell-membrane-derived nanoparticles (CMNPs) are produced using tonsil-derived mesenchymal stem cells (TMSCs) from children owing to their short doubling time. As target cell types, laryngeal cancer cells are compared to bone-marrow-derived MSCs (BMSCs) because of their cartilage damaging and chondrogenic characteristics, respectively. Treating spheroids of these cell types with CMNPs exacerbates interspheroid hypoxia with robust maintenance of the cell-cell interaction signature for 7 days. Both cell types prefer a hypoxic environment, as opposed to blood vessel formation that is absent in cartilage but is required for cancer growth. Hence, angiogenesis is inhibited by displaying the Notch-1 aptamer on CMNPs. Consequently, laryngeal cancer growth is suppressed efficiently in contrast to improved chondroprotection observed in a series of cell and animal experiments using a xenograft mouse model of laryngeal cancer. Altogether, CMNPs execute a two-edged sword function of inducing hypoxic cell-cell packing, followed by suppressing angiogenesis to promote laryngeal cancer death and chondrogenesis simultaneously. This study presents a previously unexplored therapeutic strategy for anti-cancer and chondroprotective treatment using CMNPs.

Anti-growth and pro-apoptotic effects of dasatinib on human oral cancer cells through multi-targeted mechanisms.

Dasatinib is an inhibitor of Src that has anti-tumour effects on many haematological and solid cancers. However, the anti-tumour effects of dasatinib on human oral cancers remain unclear. In this study, we investigated the effects of dasatinib on different types of human oral cancer cells: the non-tumorigenic YD-8 and YD-38 and the tumorigenic YD-10B and HSC-3 cells. Strikingly, dasatinib at 10 µM strongly suppressed the growth and induced apoptosis of YD-38 cells and inhibited the phosphorylation of Src, EGFR, STAT-3, STAT-5, PKB and ERK-1/2. In contrast, knockdown of Src blocked the phosphorylation of EGFR, STAT-5, PKB and ERK-1/2, but not STAT-3, in YD-38 cells. Dasatinib induced activation of the intrinsic caspase pathway, which was inhibited by z-VAD-fmk, a pan-caspase inhibitor. Dasatinib also decreased Mcl-1 expression and S6 phosphorylation while increased GRP78 expression and eIF-2α phosphorylation in YD-38 cells. In addition, to its direct effects on YD-38 cells, dasatinib also exhibited anti-angiogenic properties. Dasatinib-treated YD-38 or HUVEC showed reduced HIF-1α expression and stability. Dasatinib alone or conditioned media from dasatinib-treated YD-38 cells inhibited HUVEC tube formation on Matrigel without affecting HUVEC viability. Importantly, dasatinib's anti-growth, anti-angiogenic and pro-apoptotic effects were additionally seen in tumorigenic HSC-3 cells. Together, these results demonstrate that dasatinib has strong anti-growth, anti-angiogenic and pro-apoptotic effects on human oral cancer cells, which are mediated through the regulation of multiple targets, including Src, EGFR, STAT-3, STAT-5, PKB, ERK-1/2, S6, eIF-2α, GRP78, caspase-9/3, Mcl-1 and HIF-1α.

Hormone autocrination by vascularized hydrogel delivery of ovary spheroids to rescue ovarian dysfunctions.

The regeneration potential of implantable organ model hydrogels is applied to treat a loss of ovarian endocrine function in women experiencing menopause and/or cancer therapy. A rat ovariectomy model is used to harvest autologous ovary cells while subsequently producing a layer-by-layer form of follicle spheroids. Implantation of a microchannel network hydrogel with cell spheroids [vascularized hydrogel with ovarian spheroids (VHOS)] into an ischemic hindlimb of ovariectomized rats significantly aids the recovery of endocrine function with hormone release, leading to full endometrium regeneration. The VHOS implantation effectively suppresses the side effects observed with synthetic hormone treatment (i.e., tissue overgrowth, hyperplasia, cancer progression, deep vein thrombosis) to the normal levels, while effectively preventing the representative aftereffects of menopause (i.e., gaining fatty weight, inducing osteoporosis). These results highlight the unprecedented therapeutic potential of an implantable VHOS against menopause and suggest that it may be used as an alternative approach to standard hormone therapy.

Dilation-Responsive Microshape Programing Prevents Vascular Graft Stenosis.

Shape memory materials have been successfully applied to minimally invasive implantation of medical devices. However, organ-movement-specific shape programing at a microscale level has never been demonstrated despite significant unmet needs. As vein-to-artery grafting induces vein dilation and stenosis, a polymeric self-enclosable external support (SES) is designed to wrap the vascular out-wall. Its micropores are programmed to increase sizes and interconnections upon dilation. Vessel dilation promotes venous maturation, but overdilation induces stenosis by disturbed blood flow. Therefore, the unique elastic shape-fixity of SES provides a foundation to enable a stable microscale shape transition by maintaining the vein dilation. The shape transition of micropore architecture upon dilation induces beneficial inflammation, thereby regenerating vasa vasorum and directing smooth muscle cell migration toward adventitia with the consequent muscle reinforcement of veins. This game-changer approach prevents the stenosis of vein-to-artery grafting by rescuing ischemic disorders and promoting arterial properties of veins.

Directional Cell Migration Guide for Improved Tissue Regeneration.

The field of tissue regeneration has seen a paradigm shift after one wave of technological innovation after another, which has notably made significant contributions to basic cellular response control and overall tissue regeneration. One particular area that is seeing rekindled interest after technological innovation is managing cell migration toward defects because successful host cell migration from adjacent tissue can accelerate overall regeneration time in tissue defects that are either large in size or irregular in shape. This chapter surveys significant advances on directed cell migration upon topological cues. First, we introduce several examples of patterning and electrospinning technology for guiding directed cell migration, followed by a discussion on approaches to influencing radially aligned topography in pattern or electrospun sheet for overall tissue regeneration.

Polydopamine-assisted one-step modification of nanofiber surfaces with adenosine to tune the osteogenic differentiation of mesenchymal stem cells and the maturation of osteoclasts.

Adenosine and its receptors have emerged as alternative targets to control cellular functions for bone healing. However, the soluble delivery of adenosine has not proven effective because of its fast degradation in vivo. We therefore designed a stable coating of adenosine for biomaterial surfaces through polydopamine chemistry to control osteogenesis and osteoclastogenesis via A2bR signaling. First, we prepared electrospun poly (ι-lactic acid) (PLLA) nanofiber sheets, which were modified through a one-step adenosine polydopamine coating process. Scanning electron microscopy (SEM) revealed deposition of particles on the adenosine polydopamine-coated PLLA (AP-PL) sheets compared to the polydopamine-only sheets. Moreover, X-ray photoelectron spectroscopy analysis confirmed an increase in nitrogen signals due to adenosine. Furthermore, adenosine loading efficiency and retention were significantly enhanced in AP-PL sheets compared to polydopamine-only sheets. Human adipose-derived stem cells (hADSCs) cultured on AP-PL expressed A2bR (1.30 ± 0.19 fold) at significantly higher levels than those cultured on polydopamine-only sheets. This in turn significantly elevated the expression of Runx2 (16.94 ± 1.68 and 51.69 ± 0.07 fold), OPN (1.63 ± 0.16 and 30.56 ± 0.25 fold), OCN (1.16 ± 0.13 and 5.23 ± 0.16 fold), and OSX (10.01 ± 0.81 and 62.48 ± 0.25 fold) in cells grown in growth media on days 14 and 21, respectively. Similarly, mineral deposition was enhanced to a greater extent in the AP-PL group than the polydopamine group, while blocking of A2bR significantly downregulated osteogenesis. Finally, osteoclast differentiation of RAW 264.7 cells was significantly inhibited by growth on AP-PL sheets. However, osteoclast differentiation was significantly stimulated after A2bR was blocked. Taken together, we propose that polydopamine-assisted one-step coating of adenosine is a viable method for surface modification of biomaterials to control osteogenic differentiation of stem cells and bone healing.

Anti-Atherogenic Effect of Stem Cell Nanovesicles Targeting Disturbed Flow Sites.

Atherosclerosis development leads to irreversible cascades, highlighting the unmet need for improved methods of early diagnosis and prevention. Disturbed flow formation is one of the earliest atherogenic events, resulting in increased endothelial permeability and subsequent monocyte recruitment. Here, a mesenchymal stem cell (MSC)-derived nanovesicle (NV) that can target disturbed flow sites with the peptide GSPREYTSYMPH (PREY) (PMSC-NVs) is presented which is selected through phage display screening of a hundred million peptides. The PMSC-NVs are effectively produced from human MSCs (hMSCs) using plasmid DNA designed to functionalize the cell membrane with PREY. The potent anti-inflammatory and pro-endothelial recovery effects are confirmed, similar to those of hMSCs, employing mouse and porcine partial carotid artery ligation models as well as a microfluidic disturbed flow model with human carotid artery-derived endothelial cells. This nanoscale platform is expected to contribute to the development of new theragnostic strategies for preventing the progression of atherosclerosis.

Microchannel network hydrogel induced ischemic blood perfusion connection.

Angiogenesis induction into damaged sites has long been an unresolved issue. Local treatment with pro-angiogenic molecules has been the most common approach. However, this approach has critical side effects including inflammatory coupling, tumorous vascular activation, and off-target circulation. Here, the concept that a structure can guide desirable biological function is applied to physically engineer three-dimensional channel networks in implant sites, without any therapeutic treatment. Microchannel networks are generated in a gelatin hydrogel to overcome the diffusion limit of nutrients and oxygen three-dimensionally. Hydrogel implantation in mouse and porcine models of hindlimb ischemia rescues severely damaged tissues by the ingrowth of neighboring host vessels with microchannel perfusion. This effect is guided by microchannel size-specific regenerative macrophage polarization with the consequent functional recovery of endothelial cells. Multiple-site implantation reveals hypoxia and neighboring vessels as major causative factors of the beneficial function. This technique may contribute to the development of therapeutics for hypoxia/inflammatory-related diseases.

The Impact of Extramural Venous Invasion in Colorectal Cancer: A Detailed Analysis Based on Tumor Location and Evaluation Methods.

This study aimed to elucidate the prognostic implications of extramural venous invasion (EMVI) in colorectal cancer (CRC) through a meta-analysis. Eighteen eligible studies were included in this meta-analysis. Data on the prevalence of EMVI and the correlation between EMVI and survival were collected from these studies. In addition, a subgroup analysis was conducted based on tumor location and evaluation methods. The estimated prevalence of EMVI was 28.3% (95% confidence interval [CI] = 23.1% to 34.0%) in patients with CRC. The estimated prevalence of EMVI in patients with colon cancer and rectal cancer was 23.0% (95% CI = 17.6% to 29.6%) and 35.7% (95% CI = 22.3% to 51.6%), respectively. Based on the evaluation method, the estimated prevalence of EMVI were 28.3% (95% CI = 23.2% to 34.1%) and 27.3% (95% CI = 8.4% to 60.6%) in pathologic and radiologic examinations, respectively. The correlation of EMVI with worse overall and disease-free survival rates was significant (hazard ratio = 1.773, 95% CI = 1.483-2.120, and hazard ratio = 2.059, 95% CI = 1.683-2.520, respectively). However, in the subgroup analysis with radiologic examination, there was no significant difference in survival rates between patients with and without EMVI. Our study showed that EMVI was frequently detected in 28.3% of patients with CRC and was correlated to worse survival. The detection of EMVI can be useful for predicting the prognosis of patients with CRC.

Stem cell spheroids incorporating fibers coated with adenosine and polydopamine as a modular building blocks for bone tissue engineering.

Although stem cell spheroids offer great potential as functional building blocks for bottom-up bone tissue engineering, delivery of bioactive signals remain challenging. Here, we engineered adenosine-ligand-modified fiber fragments to create a 3D cell-instructive microenvironment for bone. Briefly, the Poly(ι-lactic acid) (PLLA) nanofiber sheet was partially degraded into fragmented fibers (FFs) through aminolysis and adenosine was stably incorporated via one-step polydopamine coating. The SEM and XPS analysis demonstrated that polydopamine assisted adenosine coating efficiency was significantly increased, which led to high coating efficiency of adenosine and its significant retention. The engineered fibers were then assembled into stable spheroids with human-adipose-derived stem cells (hADSCs). The adenosine in the spheroids effectively stimulated A2bR (1.768 ± 0.08) signaling, which further significantly induced the expression of osteogenic markers such as Runx2 (3.216 ± 0.25), OPN (4.136 ± 0.14), OCN (10.16 ± 0.34), and OSX (2.27 ± 0.11) with improved mineral deposition (1.375 ± 0.05 µg per spheroid). In contrast, the adipogenic differentiation of hADSCs was significantly suppressed within the engineered spheroids. Transplantation of engineered spheroids strongly induced osteogenic differentiation of hADSCs in ectopic subcutaneous tissue. Finally, the bone regeneration was significantly enhanced by implanting AP-FF group (59.97 ± 18.33%) as compared to P-FF (27.96 ± 11.14) and defect only (7.97 ± 3.76%). We propose that stem cell spheroids impregnated with engineered fibers enabling adenosine delivery could be promising building blocks for a bottom-up approach to create large tissues for regeneration of damaged bone.