{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T08:47:35Z","timestamp":1785833255189,"version":"3.56.0"},"reference-count":35,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ilikia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: Cervical integument aging is a complex, multifactorial process characterized by thinning dermis, loss of elasticity, and platysmal band prominence. Multimodal treatments targeting these distinct anatomical layers simultaneously remain limited. This study aimed to evaluate the clinical efficacy, safety, and rejuvenation potential of the STIIM UP Protocol, a single-session treatment combining calcium hydroxyapatite (CaHA), hyaluronic acid (HA), and botulinum toxin type A (BoNT-A) for neck rejuvenation. Methods: This prospective, open-label, exploratory clinical study enrolled 13 healthy women (n = 13) presenting with cervical laxity. The STIIM UP suspension was delivered bilaterally into the subdermal plane of the anterior neck region using a retro-injection fanning technique with a 22G cannula at Day 0 (D0). Evaluated outcomes included the IBSA Neck Grading Scale, Global Aesthetic Improvement Scale (GAIS), FACE-Q module scores, and high-frequency ultrasound (USG) tissue thickness measurements at baseline and Day 120 (D120). Safety was monitored throughout. Results: The median consensus IBSA scores decreased significantly from 4.0 at baseline to 2.0 at both D30 and D120 (p-value &lt; 0.01), indicating a rapid and sustained reduction in laxity. At D120, the GAIS responder rate reached 100% according to independent evaluators and 90.9% based on patient self-assessments. Quantitative USG confirmed statistically significant bilateral tissue thickening across the epidermis, dermis, and subcutaneous strata (p-value &lt; 0.05). Progressive, clinically meaningful improvements were captured via the FACE-Q scales. No local or systemic adverse events were observed. Conclusions: The STIIM UP Protocol is a safe and effective multilayer intervention that successfully achieves comprehensive neck rejuvenation, bridging immediate clinical enhancement with sustained, tissue-proven structural remodeling.<\/jats:p>","DOI":"10.3390\/jcm15156052","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T08:02:19Z","timestamp":1785830539000},"page":"6052","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The STIIM UP Protocol: Exploratory Evaluation of the Potential of Combined Calcium Hydroxyapatite, Hyaluronic Acid, and Botulinum Toxin A in Neck Rejuvenation"],"prefix":"10.3390","volume":"15","author":[{"given":"Val\u00e9ria Dal","family":"Col","sequence":"first","affiliation":[{"name":"Protocoll Clinique, Vit\u00f3ria 29055-145, ES, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassiano Santos","family":"Marchi","sequence":"additional","affiliation":[{"name":"Private Practice, Santo Andr\u00e9 09080-511, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Auxiliadora","family":"Dinalli Marchi","sequence":"additional","affiliation":[{"name":"Private Practice, Santo Andr\u00e9 09080-511, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara Barquette Silva","family":"da Rosa","sequence":"additional","affiliation":[{"name":"Private Practice, S\u00e3o Paulo 04101-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6771-5768","authenticated-orcid":false,"given":"Beatriz Domenici de","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Ilikia, S\u00e3o Paulo 01427-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nat\u00e1lia de Magalh\u00e3es","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Private Practice, Belo Horizonte 30380-403, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1bio Fernandes","family":"Ribas","sequence":"additional","affiliation":[{"name":"Protocoll Clinique, Vit\u00f3ria 29055-145, ES, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2134-473X","authenticated-orcid":false,"given":"Renata","family":"Viana","sequence":"additional","affiliation":[{"name":"Ilikia, S\u00e3o Paulo 01427-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1111\/srt.12020","article-title":"Age-related Changes in Skin Bio-mechanical Properties: The Neck Skin Compared with the Cheek and Forearm Skin in Korean Females","volume":"19","author":"Kim","year":"2013","journal-title":"Ski. Res. Technol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.25259\/CSDM_35_2022","article-title":"Characteristic Features of Neck Aging","volume":"2","author":"Vedamurthy","year":"2022","journal-title":"CosmoDerma"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1007\/s00266-022-02961-0","article-title":"Aging of the Neck Decoded: New Insights for Minimally Invasive Treatments","volume":"46","author":"Engerer","year":"2022","journal-title":"Aesthetic Plast. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e238","DOI":"10.1002\/der2.238","article-title":"Neck Aging and Rejuvenation: A Balanced Approach to Assessment and Treatment","volume":"5","author":"Roberts","year":"2024","journal-title":"Dermatol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e16658","DOI":"10.1111\/jocd.16658","article-title":"Microfocused Ultrasound in Regenerative Aesthetics: A Narrative Review on Mechanisms of Action and Clinical Outcomes","volume":"24","author":"Vachiramon","year":"2025","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.fsc.2017.12.003","article-title":"Radiofrequency Technology in Face and Neck Rejuvenation","volume":"26","author":"Gentile","year":"2018","journal-title":"Facial Plast. Surg. Clin. N. Am."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e13452","DOI":"10.1111\/srt.13452","article-title":"Efficacy of Radiofrequency Combined with Single-dot Ultrasound Efficacy for Skin Rejuvenation: A Non-randomized Split-face Trial with Blinded Response Evaluation","volume":"29","author":"Byun","year":"2023","journal-title":"Ski. Res. Technol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Paj\u0105k, J., Szepietowski, J.C., and Nowicka, D. (2022). Prevention of Ageing\u2014The Role of Micro-Needling in Neck and Cleavage Rejuvenation: A Narrative Review. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19159055"},{"key":"ref_9","first-page":"e80510","article-title":"Physiological Mechanisms and Therapeutic Applications of Microneedling: A Narrative Review","volume":"17","author":"Tehrani","year":"2025","journal-title":"Cureus"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"82","DOI":"10.25259\/CSDM_93_2023","article-title":"Skin Boosters\u2014The Upcoming Boom in Cosmetic Dermatology for Healthy Skin","volume":"3","author":"Vedamurthy","year":"2023","journal-title":"Cosmoderma"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/jocd.70875","article-title":"Skin Boosters: 2026 Updated","volume":"25","author":"Yi","year":"2026","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e2862","DOI":"10.1097\/GOX.0000000000002862","article-title":"Multimodal Radiofrequency Application for Lower Face and Neck Laxity","volume":"8","author":"Dayan","year":"2020","journal-title":"Plast. Reconstr. Surg. Glob. Open"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Jurcevic, J., and Ceovic, R. (2026). A Multimodal Approach to Facial Rejuvenation\u2014Integrating HA Fillers, Collagen Stimulators, Botulinum Toxin and Energy-Based Devices for Optimal Patient Outcomes. J. Aesthetic Med., 2.","DOI":"10.3390\/jaestheticmed2010003"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Chilukuri, S. (2025). Efficacy and Histological Evaluation of Combined Muscle Stimulation Technology, Targeted Ultrasound, and Radiofrequency for Complete Facial Rejuvenation. Med. Res. Arch., 13.","DOI":"10.18103\/mra.v13i7.6731"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1080\/09546634.2017.1395801","article-title":"Neck Rejuvenation Using a Multimodal Approach in Asians","volume":"29","author":"Doh","year":"2018","journal-title":"J. Dermatol. Treat."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ambrosio, L., Cecchini, A., Pellacani, G., and Conforti, C. (2025). Exploratory Evaluation of a Hyper-Diluted Calcium Hydroxyapatite\u2013Hyaluronic Acid Combination for Facial Rejuvenation: A Pilot Study. Cosmetics, 12.","DOI":"10.3390\/cosmetics12050212"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Dal, V., Cassiano, M., Ribas, F.F., de Paula, J.D.E., Dinalli, M.M.A., Cavalcanti, S.M.C.F., Martins, A.T.M., Ito, P.D.C., do Nascimento, A.M., and Ferreira, N.M. (2026). Enhanced Neocollagenesis and Clinical Efficacy of a Novel Regenerative Diluent for Calcium Hydroxyapatite for Facial Rejuvenation: A 90-Day Clinical Trial. Cosmetics, 13.","DOI":"10.3390\/cosmetics13020060"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e70265","DOI":"10.1111\/jocd.70265","article-title":"Dual Benefits of Calcium Hydroxyapatite Filler: A Prospective Study on Midface Volume Restoration and Skin Quality Enhancement","volume":"24","author":"Hong","year":"2025","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1093\/asj\/sjae196","article-title":"Calcium Hydroxylapatite in Regenerative Aesthetics: Mechanistic Insights and Mode of Action","volume":"45","year":"2025","journal-title":"Aesthet. Surg. J."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Amiri, M., Me\u00e7ani, R., Llanaj, E., Niehot, C.D., Phillips, T.L., Goldie, K., Kolb, J., Muka, T., and Daughtry, H. (2024). Calcium Hydroxylapatite (CaHA) and Aesthetic Outcomes: A Systematic Review of Controlled Clinical Trials. J. Clin. Med., 13.","DOI":"10.3390\/jcm13061686"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"640","DOI":"10.3390\/surgeries5030051","article-title":"Calcium Hydroxyapatite in Its Different Forms in Skin Tissue Repair: A Literature Review","volume":"5","author":"Cruel","year":"2024","journal-title":"Surgeries"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e70547","DOI":"10.1111\/jocd.70547","article-title":"Clinical and Biometric Assessment of a Hyaluronic Acid-Based Skin Booster for Face, Neck and D\u00e9collet\u00e9 Rejuvenation: A Prospective Study","volume":"24","author":"Pino","year":"2025","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"ojaf163","DOI":"10.1093\/asjof\/ojaf163","article-title":"Efficacy and Safety of Hyaluronic Acid Fillers for Horizontal Neck Lines: A Systematic Review and Meta-Analysis","volume":"8","author":"Wong","year":"2026","journal-title":"Aesthet. Surg. J. Open Forum"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Safia, A., Abd Elhadi, U., Merchavy, S., Batheesh, R., and Bathish, N. (2025). Efficacy and Safety of Hyaluronic Acid Fillers for Midface Augmentation: A Systematic Review and Meta-Analysis. Medicina, 61.","DOI":"10.3390\/medicina61101823"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"891","DOI":"10.2147\/CCID.S404248","article-title":"The Effectiveness of Injectable Hyaluronic Acid in the Improvement of the Facial Skin Quality: A Systematic Review","volume":"16","author":"Ghatge","year":"2023","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1111\/jocd.16116","article-title":"Botulinium Toxin Applications in the Lower Face and Neck: A Comprehensive Review","volume":"23","author":"Kassir","year":"2024","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"32","DOI":"10.25259\/CSDM_259_2023","article-title":"Extra Facial Esthetic Indications of Botulinum Toxin: A Review","volume":"4","author":"Arora","year":"2024","journal-title":"Cosmoderma"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Galadari, H., Galadari, I., Smit, R., Prygova, I., and Redaelli, A. (2021). Use of AbobotulinumtoxinA for Cosmetic Treatments in the Neck, and Middle and Lower Areas of the Face: A Systematic Review. Toxins, 13.","DOI":"10.3390\/toxins13020169"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1089\/fpsam.2023.0170","article-title":"Effectiveness of Botulinum Toxin-A on Face, Head, and Neck Scars: A Systematic Review and Meta-Analysis","volume":"26","author":"Rammal","year":"2024","journal-title":"Facial Plast. Surg. Aesthet. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.1111\/jocd.16296","article-title":"The Gold Protocol: A Combined Treatment Approach for Neck Rejuvenation with Calcium Hydroxyapatite, Botulinum Toxin, and Hyaluronic Acid in the Same Session","volume":"23","year":"2024","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"349","DOI":"10.2147\/CCID.S302860","article-title":"Development and Validation of IBSA Photographic Scale for the Assessment of Neck Laxity","volume":"14","author":"Tateo","year":"2021","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.fertnstert.2024.01.040","article-title":"A Brief Overview of Pilot Studies and Their Sample Size Justification","volume":"121","author":"Kunselman","year":"2024","journal-title":"Fertil. Steril."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1177\/0962280215588241","article-title":"Estimating the Sample Size for a Pilot Randomised Trial to Minimise the Overall Trial Sample Size for the External Pilot and Main Trial for a Continuous Outcome Variable","volume":"25","author":"Whitehead","year":"2016","journal-title":"Stat. Methods Med. Res."},{"key":"ref_34","first-page":"588","article-title":"A Randomized, Double-Blind, Multicenter Comparison of the Efficacy and Tolerability of Restylane Versus Zyplast for the Correction of Nasolabial Folds","volume":"29","author":"Narins","year":"2003","journal-title":"Dermatol. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1007\/s00266-022-02974-9","article-title":"The Use of the FACE-Q Aesthetic: A Narrative Review","volume":"46","author":"Ottenhof","year":"2022","journal-title":"Aesthetic Plast. Surg."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/15\/6052\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T08:37:19Z","timestamp":1785832639000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/15\/6052"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":35,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["jcm15156052"],"URL":"https:\/\/doi.org\/10.3390\/jcm15156052","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,4]]}}}