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February 22, 2026 BY
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FROM CHRONIC KNEE INJURY MODELS TO AESTHETIC REGENERATION: WHAT LYOPHILIZED UMBILICAL-CORD EXOSOMES ACTUALLY REPRESENT

BIOACTIVITY IN A CHRONIC ACL INJURY MODEL

The study “Effect of lyophilized exosomes derived from umbilical cord stem cells on chronic anterior cruciate ligament cell injury” (Lo et al., 2024) assessed whether human umbilical cord mesenchymal stem cell–derived exosomes can be lyophilized (freeze dried), stored at room temperature, rehydrated, and still preserve their biological activity.

This question is highly relevant in regenerative science, because exosomes are increasingly recognized as one of the most important biological tools for rejuvenation and repair modulation: they do not simply add factors, they actively reprogram cellular behavior through cargo transfer.

If exosomes can survive lyophilization with functional activity intact → then exosome- based regenerative strategies become operationally scalable and clinically realistic.

EXOSOMES AS SIGNAL DELIVERY UNITS

Exosomes are 30–150 nm extracellular vesicles that deliver regulatory cargo (miRNA, proteins, enzymes, lipids) capable of modulating:

● Transcriptional Programs
● Paracrine Communication
● Proliferative Potential
● Ecm Synthesis Dynamics
● Angiogenic Induction

Umbilical cord MSC–derived exosomes are particularly suitable for regenerative applications because the source tissue is developmentally young and highly secretory. Their functional effect is cargo-driven, not nutrient-driven.

ACL MODEL: WHY THIS STUDY DESIGN IS STRONG

The authors did not test on a simple acute injury model. They selected 8-week post-resection ACL cells from skeletally mature rabbits.

This is a chronic injury phenotype, with:

● Suppressed Baseline Proliferation
● Reduced Ecm Remodeling
● Disrupted Growth Factor Responsiveness

Chronic tissue is a high-stringency test. If a regenerative signal works here, the scientific weight is significantly higher

STUDY RESULTS FIND

1) Structural preservation after lyophilization + rehydration

● Mean Particle Size Remained ~85 Nm
● Positive Expression Of Alix, Tsg101, Cd9, Cd63, Cd81
● Negative For Α-Tubulin Contamination
● Consistent With Misev 2014 / 2018 Exosome Criteria

2) Efficient uptake into injured cells

● Internalized Within 6 Hours
● Dose Applied: ~1010 Vesicles Per 104 Cells

3) Functional biological impact within 24 hours

● Increased Cell Viability
● Increased Proliferation (Ki67, Edu Assays)
● Increased Migration Capacity (Transwell + Scratch Assays)

The key scientific implication is that this research provides formal evidence that lyophilized umbilical cord MSC–derived exosomes can maintain both physical vesicle identity and regenerative cargo function after storage and reconstitution. This eliminates the assumption that exosomes must remain in ultra-low temperature storage to be functional.

SCIENTIFIC RELEVANCE TO REJUVENATION AND SKIN BIOLOGY

Chronically injured ACL tissue shares core molecular hallmarks with other low- regeneration tissues: reduced cell cycling capacity, impaired ECM synthesis, altered growth factor responsiveness, and diminished angiogenic signalling.

These features are not unique to ligaments; they are common to multiple tissues with attenuated repair capacity, including aged connective tissue compartments. Therefore, the observation that lyophilized UC-MSC exosomes restored viability, proliferation, migration, and upregulated ECM and pro- regenerative gene pathways (collagen, TGF-β, VEGF, TNC, TNMD) in a chronic low-responsiveness environment supports their conceptual relevance to tissue rejuvenation biology broadly.

The biological axis demonstrated — reactivation of suppressed regenerative signaling in a model with limited intrinsic repair — is a mechanistically relevant paradigm for translation to other tissue systems where regenerative potential is compromised.

Because aged dermal fibroblasts show the same suppressed proliferative and ECM-transcriptional phenotype seen in chronic ACL cells, the ability of lyophilized UC-MSC exosomes to reactivate these pathways supports their plausible translational relevance to skin rejuvenation.

CONCLUSION

Lo et al. (2024) demonstrated that lyophilized umbilical cord–derived exosomes preserve structural identity and retain functional activity after rehydration, enhancing viability, proliferation, migration, and ECM-related gene expression in a chronic injury model. These findings support lyophilization as a viable preservation strategy and advance the feasibility of room-temperature, ready-to-use exosome preparations for regenerative medicine applications.

KEY REFERENCES

● Lo HL, Lin SY, Ho CJ, Yeh M-K, Lu C-C. Effect of lyophilized exosomes derived from umbilical cord stem cells on chronic anterior cruciate ligament cell injury. J Orthop Surg Res. 2024;19:554. doi:10.1186/s13018-024-04782-3.
● Théry C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018). J Extracell Vesicles. 2018;7(1):1535750. doi:10.1080/20013078.2018.1535750.
● Zhang B, Wu X, Zhang X, et al. Human umbilical cord mesenchymal stem cell exosomes enhance angiogenesis through the Wnt4/β-catenin pathway. Stem Cells Transl Med. 2015;4(5):513-522. doi:10.5966/sctm.2014-0267.
● Raghav PK, Khan Z, Barik S. Exosomes: from regenerative promise to therapeutic reality — mechanistic insights and translational landscape. Biomedicines. 2024;12(2):322. doi:10.3390/biomedicines12020322.
● Tan F, Liu G, Hua H, et al. Stem cell–derived exosomes: emerging tools in tissue repair and regeneration. Signal Transduct Target Ther. 2024;9:25. doi:10.1038/s41392-024-01567-7
January 18, 2025 BY
IN Uncategorized
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NAD+: FROM CELEBRITY IV TREND TO ACLINICAL CATALYST IN AESTHETIC REJUVENATION

INTRODUCTION

Once relegated to metabolic and longevity research, NAD+ (nicotinamide adenine dinucleotide) is now generating considerable interest in aesthetic medicine. While celebrity-endorsed IV drips introduced NAD+ to the public consciousness, today’s spotlight is on intradermal NAD+ injections, which aim to rejuvenate targeted areas such as the face, neck, décolleté, and hands (Conlon et al., 2022; Imai, 2014)

NAD+ : A CELLULAR POWERHOUSE

NAD+ underpins three essential skin-aging defense systems:

Mitochondrial Energy Production

Vital for ATP generation, NAD+ ensures fibroblasts have the energy to sustain collagen production (Imai, 2016).

DNA Repair via PARPs

NAD+ activates PARP enzymes, essential for fixing DNA damage— a decline in efficiency that contributes to cellular aging (Bonkowski et al., 2016).

Sirtuin-Mediated Collagen Preservation

Sirtuins (SIRT1, SIRT6), activated by NAD+ , regulate gene expression that supports collagen integrity and blocks degradative enzymes (Imai, 2016). Restoring NAD+ can re- engage these regenerative processes (Conlon et al., 2022).

EMERGING SCIENTIFIC INSIGHTS ON INJECTED NAD+

Recent investigations are shifting focus toward direct NAD+ delivery into the skin:

In Vitro Fibroblast Studies

NAD+ , especially alongside CD38 inhibition, shields fibroblasts from UV- induced damage and improves aging markers (Kang et al., 2024).

Animal UV Exposure Models

NAD+ demonstrated substantial protection against oxidative stress and inflammation in skin subjected to UV exposure (Li et al., 2023).

These findings suggest direct NAD+ injections may enhance collagen synthesis, reduce oxidative damage, and optimize cellular energy — offering a deeper, longer-lasting impact than topical or systemic treatments.

Before/After direct NAD+ injections

2025 RESEARCH HIGHLIGHTS

A surge in NAD+-targeted research underscores its growing clinical potential:

Combinatorial Injectable Formulations

A 2025 randomized study tested a rejuvenation cocktail of dual-weight hyaluronic acid, NAD+ , liposomal resveratrol, peptides, and mannitol, delivered either by microneedling or five-point intradermal injections. The injection group achieved a 55% rise in hydration and 42% in elasticity, clearly outperforming microneedling (Khademi & Lord, 2025).

As detailed in “Skin Rejuvenation with Hyaluronic Acid and Sirtuin-1 Activators (NAD+ and Resveratrol)” , benefits extended beyond clinical measures: patients reported smoother texture, enhanced radiance, and firmer skin. These results were driven by a synergistic triad:

● HA providing hydration and structure
● NAD+ restoring mitochondrial energy
● DNA repair, and resveratrol activating sirtuin-1 to stabilize collagen and reduce oxidative stress.

The injections followed a BAP-inspired five-point protocol, (Bio-Aesthetic Points), a technique using five specific injection points on each side of the face, chosen for their safety (low risk of vessels and nerves) and ability to allow the product to diffuse evenly across the skin. It is a well-established method in aesthetic medicine that ensures safe administration and optimal diffusion. This explains why injections delivered deeper penetration and greater bioavailability, producing superior outcomes. The treatment was also well tolerated, with only mild, short-lived redness or swelling — underscoring the clinical feasibility of NAD+-based injectables (Khademi & Lord, 2025).

Metabolic Health Impact

NAD+ restoration was shown to reduce inflammatory markers and improve cardiovascular metrics, including systolic blood pressure and arterial elasticity (Austin MD Clinic, 2025).

Broader Mechanistic Insights

A comprehensive review outlined how NAD+ supports mitochondrial health and counters age-associated metabolic decline, reinforcing translational potential in aesthetics (Yusri et al., 2025).

CLINICAL IMPLICATIONS FOR AESTHETIC PRACTICE

Intradermal NAD+ delivery positions itself as a molecular-level upgrade to traditional aesthetic tools. By enabling rejuvenation at the cellular core— boosting energy, repair, and collagen preservation—NAD+ injections have the potential to enhance outcomes in subtle but structurally meaningful ways, particularly in early-aging zones where conventional treatments may fall short.

The synergy with hyaluronic acid and resveratrol suggests NAD+ will be most powerful not as a standalone, but as part of advanced combination injectables designed to rejuvenate skin in both visible and structural ways.

CONCLUSION

NAD+ is not a passing trend—it is a scientifically grounded agent poised to transform regenerative dermatology. With its ability to energize mitochondria, bolster DNA repair, and activate sirtuins, NAD+ represents a multi-faceted tool for beautifying skin at its foundational level.

As new clinical trials continue to validate both its standalone and synergistic benefits, NAD+ is emerging as a cornerstone of next-generation injectable therapies, bridging the gap between beauty and cellular longevity. Joymed Care is actively monitoring these developments. As clinical trials advance, we aim to responsibly integrate NAD+–based therapies into our offerings, grounding innovation in evidence and safety.

KEY REFERENCES

● Conlon NJ et al. (2022). The Role of NAD+ in Regenerative Medicine. Plast. Reconstr. Surg.
● Imai S. (2014). Restoring NAD+ to Counteract Aging. PMC
● Imai S. (2016). NAD+ and Sirtuins in Aging. Nature Aging
● Bonkowski MS et al. (2016). Sirtuins and Aging. PMC
● Kang S et al. (2024). Exogenous NAD+ Protects Fibroblasts Against UV Stress. Cells
● Li X et al. (2023). NAD+ Reduces UV-Induced Skin Damage. Cells
● Khademi A & Lord K. (2025). Skin Rejuvenation with NAD+, Resveratrol & HA: Microneedling vs Injection Delivery. J Aesthetic Regen Med.
● Austin MD Clinic. (2025). NAD+ IV — Cardiovascular and Inflammatory Effects.
● Yusri et al. (2025). NAD+ Metabolism in Mitochondrial Homeostasis. npj Metab Health Dis.
● Khademi A, Lord K, & al. (2025). Skin Rejuvenation with Hyaluronic Acid and Sirtuin-1 Activators (Nicotinamide Adenine Dinucleotide and Resveratrol): A Comparative Clinical Study of Microneedling and Injection Delivery. J Aesthetic Regen Med.

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