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A Nanomedicine Strategy: Spatiotemporally Programmed Delivery of Engineered Exosomes via Smart Scaffolds for Craniofacial Bone Regeneration
Authors Yang Q, Ran G, Jin H, Zhai W, Lu J, Jiang W, Luo J, Fang S, Zhang Y, Liu H, Lin J
Received 5 February 2026
Accepted for publication 26 April 2026
Published 7 May 2026 Volume 2026:21 601425
DOI https://doi.org/10.2147/IJN.S601425
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Jie Huang
Qian Yang,1 Guangmei Ran,1 Hongrui Jin,1 Wentao Zhai,1 Jun Lu,1 Wenjie Jiang,1 Jingjing Luo,2 Shichang Fang,2 Yinchang Zhang,3 Huan Liu,4 Jiating Lin2
1Graduate School of Stomatology, Wannan Medical University, Wuhu, Anhui, 241000, People’s Republic of China; 2Department of Stomatology, Yijishan Hospital, Wannan Medical University, Wuhu, Anhui, 241000, People’s Republic of China; 3Department of Joint Orthopedics, Yijishan Hospital, Wannan Medical University, Wuhu, Anhui, 241000, People’s Republic of China; 4Blood Purification Center, Yijishan Hospital, Wannan Medical University, Wuhu, Anhui, 241000, People’s Republic of China
Correspondence: Jiating Lin, Department of Stomatology, Yijishan Hospital, Wannan Medical University, Wuhu, Anhui, 241000, People’s Republic of China, Tel/Fax +86-553-5739201, Email [email protected]
Abstract: The convergence of nanomedicine and regenerative biology offers new paradigms for tissue repair. The reconstruction of critical-sized bone defects, particularly within the anatomically intricate and physiologically distinct landscape of the craniomaxillofacial (CMF) region, represents a formidable frontier in regenerative medicine. Bone regeneration is not a singular biological event but a temporally orchestrated symphony, necessitating the precise, sequential coordination of immunomodulation, angiogenesis, and osteogenesis. While mesenchymal stem cell-derived extracellular vesicles (MSC-Exos) have emerged as a paradigm-shifting cell-free therapeutic - circumventing the engraftment instability, tumorigenicity, and immunogenicity limitations of live cell therapies-their clinical translation remains hindered by a fundamental kinetic mismatch: the delivery of a static, unmodulated bolus to a highly dynamic wound microenvironment. Current therapeutic strategies predominantly rely on simple injection or bulk incorporation of MSC-Exos into scaffolds. These static delivery paradigms fail to recapitulate the physiological rhythm of healing, often creating a kinetic mismatch between a single therapeutic cargo and the host’s changing needs. This review bridges a critical synthesis gap by proposing a novel “spatiotemporal programming” framework for bone regeneration. We systematically integrate cargo engineering strategies (eg, hypoxic/inflammatory priming, genetic modification) with smart biomaterial design (eg, stimuli-responsive hydrogels, core-shell scaffolds) to achieve sequential, phase-specific delivery. By aligning exosomal bioactivity with the intrinsic immuno-angiogenic-osteogenic cascade and emphasizing cargo tailoring for craniomaxillofacial specificity, this work provides a translational roadmap for next-generation, precision-guided skeletal reconstruction.
Keywords: nanomedicine, mesenchymal stem cell, exosomes, spatiotemporal delivery, bone regeneration
Introduction
The Clinical Imperative: Beyond Autografts
The clinical imperative for advanced bone regeneration strategies is driven by a staggering global epidemiological burden.1 In 2019, the global incidence of new fractures reached 178 million, driven by population growth and aging.2 While not all fractures result in massive bone voids, traumatic bone loss occurs in approximately 14.7% of open long bone fractures.2 Furthermore, critical-sized bone defects, clinically defined as osseous voids where spontaneous healing is severely impaired and regeneration capabilities are limited to less than 10% of the original structure,3 frequently result from high-energy trauma, severe infections, oncological resection (eg, ameloblastoma, osteosarcoma), or metabolic bone disorders. These conditions pose immense clinical and socioeconomic burdens.4–6 This challenge is particularly acute in the craniomaxillofacial (CMF) region. Unlike the long bones of the appendicular skeleton which develop via endochondral ossification, the maxilla and mandible predominantly arise from the cranial neural crest and ossify via intramembranous mechanisms.7,8 This distinct embryological origin confers unique biological properties such as superior turnover rates but specific susceptibility to bisphosphonate-related osteonecrosis-imposing specific regenerative requirements.9 Furthermore, CMF reconstruction is complicated by the presence of a hostile oral microenvironment characterized by a high bacterial load, complex three-dimensional geometries, and the necessity to restore not just structural integrity but also facial aesthetics and masticatory function.10–12 While autologous bone grafting remains the gold standard due to its inherent osteoconductivity, osteoinductivity, and osteogenicity, it is severely constrained by donor site morbidity (eg, pain, infection, gait disturbance) and limited graft volume.13,14
From Cellular Therapies to the Paracrine Paradigm: The Rise of MSC-Exos
To overcome the limitations of autografts, the field pivoted toward mesenchymal stem cell (MSC) transplantation. MSCs, isolated from bone marrow (BMSCs), adipose tissue (ADSCs), or oral tissues (eg, dental pulp stem cells, periodontal ligament stem cells), possess multipotency and immunomodulatory capabilities.15–17 However, the clinical translation of live cell therapies has encountered significant bottlenecks.18,19 Studies indicate that the survival rate of transplanted MSCs is dismally low, often dropping below 1% within 48 hours post-implantation due to the harsh ischemic and inflammatory microenvironment.20,21 Moreover, safety concerns regarding potential tumorigenicity, uncontrolled differentiation, and thrombosis following intravascular administration have complicated regulatory approval.22,23 Logistics regarding cold-chain storage and expensive GMP-grade cell expansion further hinder widespread adoption.24,25
Given these challenges, the paracrine hypothesis has gained significant traction.26 Accumulating evidence suggests that the therapeutic efficacy of MSCs is largely mediated not by their engraftment and differentiation, but by their secretome.27,28 Within this secretome, extracellular vesicles (MSC-Exos)-lipid-bilayer nanovesicles typically ranging from 30 to 150 nm in diameter (exosomes) have been identified as the principal bioactive components.29 MSC-exos encapsulate a complex molecular payload comprising proteins (eg, growth factors, enzymes), lipids, and nucleic acids (mRNA, miRNA, lncRNA).30 Upon internalization by recipient cells, these vesicles transfer their cargo, effectively reprogramming the recipient’s phenotype via epigenetic alterations.31,32 Compared to parental cells, MSC-Exos offer superior stability, lower immunogenicity, and the ability to traverse biological barriers such as the blood-brain barrier.33
Collectively, this positions MSC-Exos as a pivotal component of a novel nanomedicine strategy that leverages engineered natural nanocarriers for regenerative purposes. However, translating this potential into effective clinical solutions requires overcoming a fundamental kinetic mismatch.
Despite the exponential growth in MSC-Exos research, a critical synthesis gap remains: the misalignment between static delivery modalities and the dynamic nature of wound healing. Bone regeneration is a 4D process (3D space + Time) proceeding through three distinct, overlapping epochs: Phase I (inflammation): dominated by immune cell infiltration and the clearance of necrotic debris (Days 0–7).34 Phase II (repair): Characterized by angiogenesis and the formation of soft callus (Days 7–14).35 Phase III (remodeling): Involving mineralization and the re-establishment of mechanical competence (Weeks 2+).36
Treating this temporal heterogeneity with a single, unmodified dose of MSC-Exos is increasingly viewed as kinetically naive. For instance, delivering potent osteogenic factors during the acute inflammatory phase might be ineffective if the immune system is not yet transitioned to a pro-reparative state, or counterproductive if it exacerbates chronic inflammation37 (Figure 1).
 |
Figure 1 The 4D spatiotemporal cascade of bone regeneration. A schematic diagram illustrating the overlapping phases of healing: (I) inflammation (Day 0–7), characterized by M1/M2 macrophage transition; (II) angiogenesis (Day 7–14), highlighting the coupling of H-type vessels; and (III) remodeling (Week 2+), showing mineralization. The diagram contrasts static delivery (mismatched) vs. programmed delivery (matched). |
While existing reviews have separately detailed EV biogenesis or biomaterial advances, a systematic framework that integrates temporal biology, cargo engineering, and material responsiveness is conspicuously absent. This review articulates such an integrative paradigm. We first deconstruct the bone healing timeline into three actionable therapeutic windows (inflammation, angiogenesis, osteogenesis). For each phase, we synthesize the corresponding EV cargo engineering strategies and compatible smart material systems that together enable programmed release. Crucially, we emphasize the unique regenerative requirements of the craniomaxillofacial region throughout this matrix. Our goal is to move beyond a cataloguing of technologies and toward providing a design logic for building fourth-dimensional (4D) regenerative therapies.
Phase I: Modulating the Osteoimmune Environment (Days 0-7)
The premise that bone regeneration is solely an osteogenic event is a reductionist view; it is, fundamentally, an immune-driven cascade where the initial inflammatory milieu dictates the downstream fate of osteoprogenitors.38,39 Following trauma or implantation, the rapid infiltration of neutrophils and monocytes establishes an osteoimmune microenvironment. While acute inflammation is a prerequisite for debridement and chemotaxis, the persistence of a pro-inflammatory M1 macrophage phenotype inevitably leads to chronic inflammation, fibrotic encapsulation, and impaired osseous integration.40,41 Thus, the primary objective of any spatiotemporal delivery system in the first 3–7 days must be precise immunomodulation-forcing a phenotype switch from M1 to pro-reparative M2 macrophages.42
Epigenetic Reprogramming via EV Cargo
MSC-Exos function as potent nanocarriers capable of recalibrating the immune balance.43 Unlike traditional anti-inflammatory drugs that passively suppress cytokine production, MSC-Exos actively modulate macrophage phenotypes through the horizontal transfer of bioactive nucleic acids.44–46
MiRNA-Mediated Switching
Specific exosomal miRNAs act as epigenetic switches. For instance, miR-223 derived from MSC-Exos has been shown to target the Pknox1 gene, thereby suppressing pro-inflammatory polarization and accelerating the transition to a reparative state.47,48 Similarly, miR-146a inhibits the NF-κB signaling pathway by targeting IRAK1 and TRAF6, effectively braking the inflammatory cascade.49,50 This is particularly relevant in the oral CMF environment, where a high bacterial load can perpetuate M1 polarization, making early and effective immunomodulation paramount.
The TLR4 Paradox
Interestingly, investigations utilizing monocytic cell lines demonstrate that MSC-Exos can activate TLR4 signaling to trigger nuclear translocation of NF-κB in a manner that, paradoxically, induces an M2 phenotype characterized by high IL-10 and low IL-12 expression.51,52 This implies that the therapeutic efficacy of MSC-exos relies on a specific instruction set that educates rather than merely suppresses the immune system.
Potentiating Efficacy Through Inflammatory Priming
While naive MSC-exos possess inherent immunomodulatory properties,53 their basal potency often proves insufficient to counteract the robust cytokine storm typical of critical-sized defects. To address this, inflammatory priming (or licensing) has emerged as a requisite engineering strategy.54
TNF-α Preconditioning
Research indicates that culturing MSCs in the presence of inflammatory mediators, such as TNF-α, mimics the injury environment.55 This stress test compels the cells to package a more potent anti-inflammatory payload.56 TNF-α-preconditioned MSC-Exos have been shown to possess a superior capacity to induce M2 macrophage polarization and downregulate COX-2 and pro-inflammatory interleukins compared to their naive counterparts.57,58
IL-1β Preconditioning
Similarly, pretreatment with IL-1β enriches MSC-exos with miR-146a, a known negative regulator of innate immune responses, which effectively inhibits inflammation in sepsis models.59,60 Consequently, for Phase I of a programmed delivery strategy, utilizing primed exosomes represents a critical design choice to ensure sufficient immunomodulatory efficacy.
However, it is crucial to recognize that macrophage polarization is a highly dynamic, context-dependent, and metabolically regulated process, rather than a simple unidirectional M1-M2 switch.61 While MSC-Exos can induce epigenetic changes, the long-term stability and predictability of this reprogramming remain uncertain.62 Furthermore, although inflammatory priming utilizes innate immune training to direct macrophages toward a reparative phenotype, it introduces significant challenges.63 These include the potential for pathogenic overactivation, the unintentional induction of immune tolerance, and unpredictable shifts due to high cellular plasticity in varying microenvironments.64 Therefore, the precise timing and spatial regulation of MSC-Exo delivery—tightly controlling the dosage to match the specific inflammatory phase—are paramount in determining the ultimate clinical outcomes.
Material Logic: The Burst Release Requirement
The biological imperative to resolve inflammation early imposes specific kinetic requirements on the biomaterial carrier.65 Unlike the sustained release required for osteogenesis, the immunomodulatory cargo must be bioavailable immediately post-implantation to intervene before the onset of chronic inflammation.66
Stimuli-Responsive Hydrogels
Current hydrogel strategies, such as those employing gelatin methacryloyl (GelMA) or hyaluronic acid, can be engineered to degrade in response to high concentrations of matrix metalloproteinases (MMPs) or acidic pH present in the inflammatory microenvironment.67,68
On-Demand Release
Rather than passive diffusion, this stimuli-responsive degradation achieves true on-demand exosome release through targeted cleavage mechanisms.69 For instance, localized pH drops (pH ~6.0) or MMP overexpression during acute inflammation triggers the cleavage of specific peptide crosslinkers within the hydrogel network.70 This rapid decrease in crosslinking density facilitates a programmed burst release—often delivering a substantial, quantifiable fraction (eg, >60%) of the immunomodulatory EV cargo within the critical first 48–72 hours post-implantation.71 This targeted kinetic profile significantly reduces macrophage infiltration and promotes early healing compared to nonresponsive controls.72
While promoting the M1-to-M2 transition is critical, a dialectical examination reveals that more is not always better.73 Sustained M2 activity involves the secretion of TGF-β1 and PDGF, factors that-if unchecked-promote fibroblast proliferation and collagen deposition rather than osteogenesis.74,75 This can result in fibrotic encapsulation of the implant.76,77 Therefore, the ultimate goal of Phase I engineering is the temporal confinement of the M2 switch, providing a transient immunomodulatory pulse.78
Phase II: Coupling Angiogenesis with Osteogenesis (Days 7-14)
Once the initial inflammation begins to subside, the metabolic demand of the regenerating tissue increases exponentially.79,80 Oxygen and nutrient supply become the rate-limiting steps for tissue growth.81 However, successful osseous reconstruction requires more than generic vascularization; it depends on the precise formation of Type H vessels, a specific capillary subtype that actively couples angiogenesis with osteogenesis by creating a niche for osteoprogenitor recruitment.82,83 The coupling of angiogenesis and osteogenesis via Type H vessels is a fundamental process in intramembranous ossification, the primary mode of jawbone formation, underscoring its therapeutic relevance for CMF defects (Figure 2).
 |
Figure 2 Cargo engineering strategies. Illustration of three primary engineering approaches: (A) Priming: MSCs under hypoxia or TNF-α stimulation releasing enhanced MSC-Exos; (B) Genetic Modification: transfection of MSCs to overexpress BMP-2/miRNAs; (C) Parental Cell Selection: neural crest-derived oral MSCs (DPSCs/PDLSCs) for CMF specificity. |
Hypoxia-Driven Cargo Enrichment
Following the establishment of a pro-regenerative immune milieu in Phase I, the regenerative cascade enters a phase critically dependent on new nutrient supply. The physiological hypoxic niche of bone fractures suggests that oxygen tension is a critical regulator of EV payload.84
Hypoxic Preconditioning
Research demonstrates that culturing MSCs under low oxygen tension (eg, 1%) stabilizes hypoxia-inducible factor-1α (HIF-1α) in parental cells.85 This leads to a specific enrichment of angiogenic cargos within the secreted vesicles.86
The miR-126/SPRED1 Axis
Most notably, hypoxic MSC-Exos exhibit significantly upregulated levels of miR-126 compared to their normoxic counterparts.87 Mechanistically, exosomal miR-126 functions by targeting and suppressing SPRED1 (Sprouty-related EVH1 domain-containing protein 1), a negative regulator of the Ras/ERK pathway.88 The consequent activation of Ras/ERK signaling in recipient endothelial cells robustly promotes migration, tube formation, and the formation of functional vascular networks.89,90
HIF-1α Transfer
Furthermore, studies utilizing mutant HIF-1α -modified MSCs confirm that MSC-Exos can directly transfer HIF-1α protein to recipient cells, further potentiating the angiogenic response.91
Despite these advantages, the hypoxia-driven cargo enrichment approach faces notable challenges and limitations in actual therapeutic contexts. The precise degree and duration of hypoxia are difficult to standardize across different cell batches, leading to potential heterogeneity in the exosomal payload.92 Furthermore, extreme or prolonged hypoxic stress might inadvertently cause MSCs to package deleterious or pro-apoptotic factors alongside angiogenic cues, presenting a complex risk-benefit profile that requires rigorous optimization to ensure safety and efficacy.93
Implications for Material Design: Sequential Release Kinetics
To align with the physiological healing timeline, the delivery of these angiogenic accelerators must be kinetically distinct from the initial immunomodulatory burst.94
Core-Shell Scaffolds
This kinetic control can be achieved through core-shell scaffold designs or double-layered hydrogels.95 For instance, the rapid degradation of an outer layer (releasing Phase I immunomodulatory MSC-Exos) exposes an inner core engineered for the delayed, sustained release of Phase II hypoxic MSC-Exos.96,97
Hydrolytic Delays
Strategies using triblock polymer microspheres attached to nanofibrous scaffolds have been shown to delay exosome release until polymer hydrolysis occurs.98 This effectively creates a therapeutic window (typically starting around 3–5 days) that aligns with the peak requirement for vascular invasion.99
Phase III: Orchestrating Osteogenesis and Remodeling (weeks 2-8+)
The culmination of the regenerative cascade is the deposition of a mineralized matrix and its subsequent remodeling. Unlike the transient signaling required for immunomodulation, this phase necessitates sustained osteoinductive cues to drive the differentiation of recruited mesenchymal progenitors and to maintain the delicate homeostatic equilibrium between osteoblastic formation and osteoclastic resorption.100,101
Amplifying the Osteoinductive Signal via Genetic Engineering
While naive MSC-Exos possess baseline osteoinductive capacity, their efficacy in critical-sized defects is often rate-limited by the insufficient concentration of specific morphogens.102
BMP-2 Potentiation
MSCs engineered to constitutively overexpress BMP-2 secrete exosomes that do not necessarily carry the BMP-2 protein itself, but rather a reprogrammed miRNA payload (eg, miRNAs targeting SMURF1 and SMAD7) that potentiates the BMP signaling cascade in recipient cells.103,104 This acts as a sophisticated epigenetic amplification mechanism.
Silencing Inhibitors
Similarly, exosomes derived from MSCs overexpressing miR-20a have been shown to robustly promote osteointegration by targeting BAMBI, thereby disinhibiting the ALK/Smad pathway.105 Furthermore, modification with neural EGFL-like 1 (Nell1) protein results in the downregulation of miR-25-5p, enhancing osteogenesis via the suppression of Smad2 phosphorylation.106
Optimizing Cargo for the Jaw: The Homology Advantage
Upon the groundwork of immunomodulation and nascent vascularization laid in the preceding phases, the ultimate challenge of mineralized tissue deposition and remodeling comes to the fore. Evidence suggests that origin matters. Jawbones have a distinct healing capacity compared to long bones, attributed to their neural crest origin.107
Lineage Specificity
MSC-Exos derived from oral tissues (eg, DPSCs, PDLSCs) may possess superior osteoinductive potency for CMF defects due to lineage homology. DPSC-exos have been shown to robustly promote angiogenesis and osteogenesis in alveolar bone defects by activating the p38 MAPK pathway.108
Periodontal Defense
Furthermore, PDLSC-Exos carrying miR-155-5p effectively regulate the Th17/Treg balance in periodontitis-induced bone loss, addressing the unique immuno-infectious challenges of the oral cavity.109,110
Implications for Material Design: Long-Term Retention
The kinetic challenge of Phase III lies in maintaining therapeutic concentrations of MSC-Exos over weeks to months.
PLGA Microspheres
Porous microspheres fabricated from poly (lactic-co-glycolic acid) have demonstrated the capacity to sustain the release of hypoxic MSC-exos for up to 21 days.111
Bioactive Glass Hybrids
Encapsulating MSC-Exos within the micropores of hierarchical mesoporous bioactive glass scaffolds protects them from enzymatic degradation while allowing for the slow, diffusion-controlled release necessary for prolonged osteogenic stimulation.112 This long-term release profile must also contend with the dynamic mechanical forces of the masticatory system, requiring scaffolds that provide both biological cues and mechanical stability unique to the CMF skeleton.
Safety Considerations
Constitutive overexpression of BMP-2 or inhibition of negative regulators could theoretically lead to ectopic bone formation or soft tissue swelling.113 Future clinical translation may necessitate inducible systems (eg, Tet-On/Off promoters) where the production of therapeutic cargo in parental cells can be externally regulated114 (Figure 3).
 |
Figure 3 Smart material delivery systems. (A) pH-responsive hydrogels for burst release of immunomodulatory MSC-Exos. (B) Core-shell fibers for sequential release of angiogenic MSC-Exos. (C) PLGA microspheres for sustained retention of osteogenic MSC-Exos. |
Biocompatibility and Biosafety of Intelligent Exosome-Based Scaffolds
As the field transitions toward clinical translation, evaluating the biocompatibility and biosafety of programmed delivery systems is paramount. While MSC-Exos circumvent the tumorigenicity and uncontrolled engraftment risks of live-cell therapies by leveraging their intrinsic low immunogenicity, their integration into smart biomaterials introduces complex safety considerations.115,116 Hydrogels have been widely recognized as a favorable platform for exosome delivery due to their excellent baseline biocompatibility, tunable physicochemical properties, and extracellular matrix (ECM)-mimetic nature.117 Furthermore, recent advancements in 2026 have demonstrated that stimulus-responsive biomaterials, such as 3D-printed coaxial hydrogel scaffolds, can construct delivery systems that are safe, controllable, and highly efficient, maintaining excellent localized biocompatibility while modulating the osteoimmune environment.118 However, emerging 2026 studies emphasize that the regulatory considerations regarding the long-term toxicity and biosafety of these composite systems must be rigorously evaluated.117,119 A primary concern is that the degradation byproducts of stimuli-responsive polymers—such as specific acidic monomers or crosslinker remnants following pH- or enzyme-targeted cleavage—must not provoke a secondary immune response or exhibit localized cytotoxicity.118,119 The biosafety profile must also account for the complete long-term clearance of these engineered scaffolds from the anatomically complex craniomaxillofacial region.120 Another critical biosafety challenge is the potential for ectopic bone formation or pathological soft tissue ossification, particularly when utilizing scaffolds loaded with highly potent, genetically modified exosomes (eg, BMP-2 overexpressing exosomes).121 Ultimately, ensuring systemic safety requires rigorous pharmacokinetic tracking and strict manufacturing standardization to verify that the encapsulated exosomes remain localized to the target defect, minimizing off-target dissemination while concurrently addressing both inflammation and regeneration safely.115,117
Summary: The Spatiotemporal Engineering Matrix
To synthesize the diverse strategies discussed, we propose a spatiotemporal engineering matrix (Table 1).
 |
Table 1 Spatiotemporal Engineering Matrix for Programmed Bone Regeneration |
Conclusion and Outlook
Bone regeneration is fundamentally a 4D process. The prevailing static delivery paradigms are kinetically inadequate and biologically insufficient for critical-sized defects. By converging cargo engineering (eg, hypoxic priming, genetic modification) with stimuli-responsive biomaterials, we can now “program” the sequential release of bioactive cues to match the intrinsic rhythm of healing.
However, it is crucial to acknowledge that there are still significant challenges and unanswered questions that require further investigation before widespread clinical use. Currently, while native exosomes have entered early-phase clinical trials for various systemic conditions, direct human clinical data specifically evaluating “intelligent exosome-based scaffolds” for bone regeneration remains virtually non-existent.122 The translation of this spatiotemporal matrix faces severe clinical hurdles. First, the “standardization crisis” in EV biomanufacturing demands scalable, reproducible processes coupled with rigorous potency assays.123–125 Additionally, navigating the regulatory landscape is challenging, as these intelligent scaffolds are classified as highly complex combination products.122 Key frontiers include: (1) the integration of external triggers (eg, near-infrared light, ultrasound) for on-demand, pulsatile EV release;118,126 (2) the development of CMF-specific molecular signatures to guide personalized exosomal cargo selection; and (3) the engineering of feedback loops where EVs themselves report on the local microenvironment to dynamically adjust subsequent release. By synchronizing our therapeutic interventions with the patient’s unique immuno-angiogenic-osteogenic axis, we can truly unlock the precision potential of cell-free regenerative medicine.
Ethics Approval
This study was approved by the Ethics Committee of Wannan Medical University with relevant guidelines.
Funding
This work was supported by Anhui Provincial Health and Wellness Research Project (AHWJ2023A10146), and the Scientific Research Foundation Project for Introducing Talents of Yijishan Hospital, Wannan Medical University (YR202117).
Disclosure
The authors confirm that there are no competing interests regarding the publication of this paper.
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