靶区治疗分区框架：非交联透明质酸改善皮肤质量的临床分区策略

Abstract 原文摘要

ABSTRACT

BackgroundAesthetic medicine has progressively shifted from volume toward skin quality as a key determinant of perceived age and facial attractiveness. Although non–cross‐linked hyaluronic acid–based injectables are widely used to improve skin hydration and appearance, clinical application remains largely technique‐driven, and structured decision‐making frameworks addressing skin texture and visual skin quality as distinct therapeutic objectives remain limited.

ObjectiveTo introduce target treatment zones (TTZs), a skin quality‐first, anatomy‐guided decision‐making framework within the visual aesthetic (VA) methodology, designed to support selective dermal intervention for texture refinement and patient‐perceived improvement in skin quality without altering facial volume or contour.

MethodsEvidence on skin quality as a foundational aesthetic parameter was reviewed alongside the rationale for dermal texture refinement using non–cross‐linked hyaluronic acid combined with glycerol. The TTZ framework integrates anatomical zoning, zone‐specific clinical relevance, and biologically appropriate dermal depth selection. Illustrative clinical cases from routine aesthetic practice are included to demonstrate clinical feasibility, practical application, and conceptual understanding rather than objective efficacy.

ResultsThe illustrative cases supported the practical application of the TTZ framework for identifying clinically relevant treatment zones and selecting localized dermal intervention while seeking to minimize overtreatment. Serial clinical observations suggested possible improvements in hydration, surface texture refinement, and visual skin quality without volumetric change or contour distortion, while changes in skin texture homogeneity, fine superficial lines, pore appearance, and perceived skin brightness were observed. No formal efficacy analysis was performed.

ConclusionTTZs are proposed as a conceptual clinical framework that may support the incorporation of skin quality enhancement as a structured planning step rather than as a solely technique‐dependent intervention. As an extension of the VA methodology, TTZs are intended to complement structural rejuvenation strategies and support natural, skin‐centered aesthetic outcomes.

Keywords: aesthetic medicine、hyaluronic acid、skin quality、target treatment zones、visual aesthetic methodology

1

Introduction

The focus of aesthetic medicine is shifting from an isolated correction of wrinkles and volume loss toward a comprehensive assessment of facial aging as a multilayered process [ 1 ]. While volumetric restoration and contour modification remain central to facial rejuvenation, these strategies alone do not fully address age‐related changes in skin texture, hydration, and visual quality. Skin quality is being increasingly recognized as an independent contributor to perceived age, facial attractiveness, and patient satisfaction [ 2 , 3 ].

To meet this evolving standard of care, aesthetic therapies have advanced to target these specific physiological markers. Non–cross‐linked hyaluronic acid (HA)–based injectable formulations, commonly referred to as hydroboosters, are treatments that contain HA and other ingredients that deeply hydrate skin, smooth fine lines, and improve elasticity and visual properties by replenishing moisture and stimulating collagen production in the dermis. The primary mechanism of action of these injectable formulations extends beyond a simple volume augmentation to the fundamental modification of the skin's viscoelastic properties. These formulations, which may incorporate a combination of HA and glycerol, can function as a moisture depot, improving cell turgor and tissue tension [ 4 ]. At the cellular level, non–cross‐linked HA–based injectable formulations can act as bioactive scaffolds that attenuate the catabolic profile of aging skin. Chen et al. [ 5 ] demonstrated that a complex of low‐molecular‐weight sodium hyaluronate and its acetylated derivative can enhance Type I collagen accumulation in fibroblasts. Preclinical evidence suggests that HA complexes can downregulate matrix metalloproteinase‐1, the enzyme primarily responsible for collagen fragmentation in photoaged skin. Simultaneously, these complexes synergistically increase the secretion of Type I collagen, mitigating the age‐related dermal thinning [ 6 ].

At present, hydroboosters have seen use within the prejuvenation demographic: younger individuals seeking preventative treatments to delay the onset of aging [ 7 ]. A 2022 consensus of aesthetic practitioners across the Asia‐Pacific region established four specific emergent perceptual categories to standardize the definition of skin quality: skin tone evenness, skin surface evenness, skin firmness, and skin glow. These categories include measurable attributes such as pigmentation, redness, pores, fine lines, elasticity, and hydration [ 8 ]. Within this framework, the expert panel highlighted distinct regional preferences, noting that Asian patients tend to desire a more even and luminous skin appearance when compared with the preference of Caucasian patients. Uneven skin tone, uneven skin surface, skin laxity, as well as sebaceous gland hyperactivity and enlarged pores were identified as the most common skin quality issues encountered in clinical practice in Asia [ 8 ].

The visual aesthetic (VA) methodology was developed as a strategic framework for facial rejuvenation, concentrating on proportion, framework, sagginess, and projection as core analytical pillars [ 2 ]. Building upon this foundation, the present work introduces target treatment zones (TTZs) as a conceptual extension that specifically focuses on skin quality enhancement. TTZs aim to support structured, anatomy‐guided decision‐making for superficial dermal treatment, focusing on dermal texture and visual skin quality without altering facial volume or contour. At present, TTZs should be considered a conceptual clinical framework rather than a validated clinical guideline or standardized treatment protocol.

2

Skin Quality as a Foundational Aesthetic Parameter

2.1

Defining Skin Quality

Skin quality comprises several interrelated parameters, including surface texture homogeneity, fine superficial wrinkles, pore visibility, hydration status, elasticity, and radiance. Alterations in these parameters may occur early in the aging process and persist independently of volumetric or structural changes. Clinically, compromised skin quality often presents as reduced skin brightness, uneven texture, or a fatigued appearance, even in patients without significant contour deficiency [ 1 ].

From an aesthetic perspective, deterioration in skin quality can diminish an otherwise appropriate structural rejuvenation. Consequently, interventions targeting dermal hydration and texture refinement may play an essential role in both prejuvenation strategies for younger patients and rejuvenation approaches for older individuals.

2.2

Skin Quality Versus Volume and Contour

Volumetric correction primarily targets the deep anatomical layers, including skeletal support and fat compartments, to restore facial structure and contour [ 9 , 10 ]. In contrast, skin quality‐focused interventions target the papillary and upper reticular dermis. While complementary within the VA methodology, these approaches have distinct therapeutic objectives and are not interchangeable [ 2 , 9 ].

In patients with thin skin, reduced elasticity, or advanced dermal deterioration, reliance on volumetric correction alone may necessitate excessive filler use, increasing the risk of overcorrection and unnatural outcomes. Prioritizing skin quality enhancement in such cases may improve skin elasticity and firmness, reduce dependency on volume, and support more natural facial harmony.

3

Biological Rationale for Dermal Texture Refinement

3.1

Role of Non–Cross‐Linked HA

HA is a fundamental component of the extracellular matrix, contributing to dermal hydration, viscoelasticity, and tissue homeostasis. Unlike cross‐linked HA, non–cross‐linked HA is rapidly metabolized by endogenous hyaluronidases present in the skin, typically within a day [ 11 ]. Therefore, its lasting clinical benefits are derived from natural biological responses and improved hydration rather than a long‐term physical structure. When injected into the dermis, non–cross‐linked HA formulations integrate within the extracellular matrix to hold water without adding persistent volume [ 4 , 11 ].

This increased matrix hydration significantly improves the dermal microenvironment beyond just passively boosting moisture. Fibroblasts may respond favorably to these enhanced extracellular conditions, which potentially support collagen homeostasis and dermal integrity without reliance on volumetric expansion [ 5 , 12 ].

3.2

Dermal Depth Considerations

Within the TTZ framework, dermal delivery is specifically directed toward the papillary–upper reticular dermal interface, corresponding to an approximate depth of 1 mm. This plane provides access to a high density of metabolically active fibroblasts while potentially minimizing surface irregularities associated with overly superficial injections and avoiding volumetric effects seen with deeper placement [ 11 ].

3.3

Role of Glycerol in Dermal Hydration

Glycerol is a well‐established humectant with a recognized role in maintaining skin hydration and barrier function [ 13 ]. Within the dermal environment, glycerol attracts and retains water, supports epidermal barrier integrity, and reduces trans‐epidermal water loss [ 13 ]. When co‐administered with HA via microinjections, glycerol acts synergistically to stabilize interstitial fluid retention and provide a sustained dermal moisture depot [ 4 ]. In vivo biophysical evaluations have demonstrated that this injected combination significantly improves cell turgor, tissue tension, and the physiological environment of the extracellular matrix, leading to improvements in viscoelastic skin properties such as firmness and fatigue resistance [ 4 ]. When combined with non–cross‐linked HA, glycerol may also stabilize dermal hydration and contribute to enhancement of visual skin quality [ 14 , 15 ].

4

TTZs: A Skin Quality‐First Framework

TTZs represent a skin quality‐focused extension of the VA methodology. Rather than functioning as an injection map or procedural protocol, TTZs are intended to provide a structured decision‐making framework that guides clinicians in determining where intervention to improve skin quality may be most relevant and why a specific region warrants prioritization.

4.1

Anatomical Organization

The TTZ framework divides the face and neck into clinically relevant regions, including the frontal, temporal, zygomatic, sub‐zygomatic, cheek, jowl, and peri‐oral zones (Figure 1 ). Each zone is associated with distinct patterns of dermal aging, biomechanical behavior, and aesthetic relevance. The framework is adaptable and does not mandate intervention across all zones in every patient.

FIGURE 1 Schematic illustration of the target treatment zone framework, highlighting anatomically and functionally defined regions for aesthetic intervention. CZ, cheek & infraorbital zone; JZ, jowl zone; OZ, peri‐oral zone; SZ, sub‐zygomatic zone; TZ, temporal zone; ZZ, zygomatic zone.Within this framework, a zone is considered for skin quality‐focused intervention only when localized concerns are present, such as dryness, visibly dilated pores, fine or static superficial wrinkles, surface texture irregularities, including atrophic or acne scarring, or reduced visual skin quality. The presence of one or more of these features supports prioritization of the corresponding zone, independent of volumetric or structural considerations.

4.2

Clinical Objectives

The objective of TTZ‐guided intervention is to address localized impairments in skin quality by potentially improving surface homogeneity and dermal hydration, which may support enhancement of visual skin quality. For the purposes of the framework, high visual skin quality is defined by an increased light reflection and decreased shadowing resulting from improved surface homogeneity, minimized pore visibility, and attenuated fine lines. While currently assessed via standardized clinical photography and patient‐reported outcomes [ 2 ], future approaches should incorporate objective tools such as glossmeters, reflectometers, or polarized imaging systems to quantify these changes in surface reflectance. This framework is designed to complement, rather than replace, structural or volumetric rejuvenation strategies while preserving facial contour, proportion, and natural dynamics.

5

Clinical Application of the Framework

5.1

Study Design and Case Selection

The cases provided in this study are illustrative and descriptive in nature and are not intended to demonstrate clinical efficacy, establish comparative outcomes, or support protocol standardization. No statistical comparisons were performed. Cases were retrospectively selected from routine aesthetic practice to demonstrate the application of the framework in patients requiring targeted skin quality improvement. The primary selection criterion was the clinical presentation of localized skin quality impairments, including enlarged pores, reduced firmness, coarse surface texture, and fine superficial wrinkles. Additionally, the selected patients presented without clinically significant volumetric deficiency or facial laxity. This highlights the framework's focus on superficial dermal intervention rather than structural restoration.

5.2

Patient Selection

Patient selection should include assessment of treatment indications and relevant contraindications before TTZ identification and treatment planning. Proposed contraindications within the present framework are summarized in Table 1 , while the proposed clinical decision‐making process for patient screening, TTZ selection, treatment, and follow‐up is summarized in Figure 2 .

TABLE 1 Absolute and relative contraindications for hyaluronic acid–glycerol skin‐booster treatment within the TTZ framework.

FIGURE 2 Decision‐making flowchart for daily‐practice selection of TTZs in hyaluronic acid–glycerol skin‐booster (hydrobooster) treatment. Patient candidacy is first confirmed, and C/I are classified as absolute, relative, or none. Absolute C/I warrants discontinuation of treatment with consideration of an alternative modality; relative C/I permits treatment following counseling, informed consent, and documentation. Baseline photographs are obtained before treatment. TTZs are then identified according to zone‐specific indication. The lower eyelid is excluded from treatment in all cases owing to thin dermal architecture and increased risk of edema and product visibility. The product is delivered into the mid‐to‐deep dermis using a 30–32‐gauge needle in approximately 0.025‐mL micro‐depots per injection point, distributed across the selected zone(s). Standardized follow‐up photographs are taken at 1, 2, and 3 months post‐application; three sessions at 4‐ to 6‐week intervals are recommended per study protocol. Diamond, decision point; teal, process step; dark teal, start/end; amber, proceed with caution; dark red, discontinue treatment; C/I, contraindications; TTZ, target treatment zone.5.3

Framework Intervention Principles

TTZs are intended to function as a conceptual planning layer within facial aesthetic assessment. Zone selection is guided by individual patient concerns, anatomical characteristics, and baseline skin quality rather than predefined treatment protocols. Clinical application focuses on biologically appropriate dermal targeting with pinpoint injection of the non–cross‐linked HA–based formulation into the TTZs (Figure 3 ) with the aim of supporting hydration and texture refinement without inducing volumetric change.

FIGURE 3 Schematic representation of HB injection into the target treatment zones. The product is administered into the mid‐to‐deep dermis using a 30–32 G sharp needle, delivering micro‐depots of approximately 0.025 mL per injection point in a distributed pattern. This technique is intended to enhance dermal hydration and improve surface skin quality without inducing a volumetric effect. The lower eyelid region is excluded due to its thin dermal architecture and higher susceptibility to edema and visibility of the injected product. HB, hydrobooster.5.4

Illustrative Case Applications

5.4.1

Case 1

A 29‐year‐old Thai female presented with enlarged pores, reduced skin firmness, coarse surface texture, and mild atrophic acne scarring, without facial laxity or structural volumetric deficiency (Figure 4 ). Selective superficial dermal intervention was performed according to the TTZ framework. Serial clinical observation suggested improved hydration, refinement of pore appearance, and progressive smoothing of surface texture while appearing to preserve facial contour and expression.

FIGURE 4 TTZs used in the treatment for a 29‐year‐old female as well as follow‐up improvements over 3 months. (A) TTZ map, (B) before treatment, (C) after 1 month, (D) after 2 months, and (E) after 3 months. CZ, cheek & infraorbital zone; JZ, jowl zone; SZ, sub‐zygomatic zone; TTZ, target treatment zone; TZ, temporal zone; ZZ, zygomatic zone.5.4.2

Case 2

A 25‐year‐old male presented with enlarged pores, fine periorbital lines, and reduced skin hydration associated with reduced visual skin quality, without structural volumetric deficiency (Figure 5 ). TTZ‐guided intervention was performed over three sequential sessions at monthly intervals. Serial clinical observation suggested attenuation of fine superficial lines, refinement of pore appearance, and gradual improvement in surface smoothness and perceived skin brightness over 3 months.

FIGURE 5 TTZs used in the treatment for a 25‐year‐old male as well as follow‐up improvements over 3 months. (A) TTZ map, (B) before treatment, (C) after 1 month, (D) after 2 months, and (E) after 3 months. CZ, cheek & infraorbital zone; JZ, jowl zone; SZ, sub‐zygomatic zone; TTZ, target treatment zone; TZ, temporal zone; ZZ, zygomatic zone.5.4.3

Case 3

A 52‐year‐old Thai female presented with coarse skin texture, fine superficial wrinkles, and reduced visual skin quality without clinically significant volumetric deficiency (Figure 6 ). TTZ‐guided intervention was performed over three sequential monthly sessions. Serial clinical observation suggested progressive improvement in surface texture, fine wrinkles, and perceived skin brightness over a three‐month period, while facial contour and expression appeared to remain unchanged.

FIGURE 6 TTZs used in the treatment for a 52‐year‐old female as well as follow‐up improvements over 3 months. (A) TTZ map, (B) before treatment, (C) after 1 month, (D) after 2 months, and (E) after 3 months. CZ, cheek & infraorbital zone; JZ, jowl zone; OZ, peri‐oral zone; SZ, sub‐zygomatic zone; TTZ, target treatment zone; TZ, temporal zone; ZZ, zygomatic zone.6

Discussion

Facial rejuvenation may not be fully achieved through volumetric correction alone. Skin quality deterioration independently contributes to perceived aging and patient dissatisfaction [ 1 , 2 ]. Despite widespread use of dermal hydration therapies, a lack of structured planning frameworks has limited consistency and strategic integration.

TTZs are intended to address this gap by reframing skin quality enhancement as a methodological decision‐making step rather than a technique‐driven intervention. By emphasizing anatomical relevance, indication‐driven prioritization, and biologically appropriate dermal targeting, TTZs may facilitate integration effectively within the VA methodology and help support natural, balanced aesthetic outcomes. The novelty of the TTZ framework lies in structured zone prioritization and indication‐based treatment planning.

The descriptive changes observed in the illustrative cases are broadly consistent with established literature regarding the dual‐action mechanism of chemically non–cross‐linked HA complexes. Existing evaluations have highlighted the biphasic nature of these interventions, which consists of an immediate phase and a delayed phase [ 16 , 17 ]. Initially, patients may experience an immediate hydration benefit perceived as a subtle plumping effect due to the hygroscopic properties of the injected matrix. Over time, this transitions into a delayed remodeling phase characterized by mechanical fibroblast activation and subsequent collagen stimulation, ultimately restoring elasticity and providing improved dermal firmness and elasticity. Further in vitro evidence supports this stimulatory effect. A 15% increase in fibroblast viability and a 9.7‐fold upregulation of Type I collagen gene expression were observed following exposure to an HA‐based formulation, confirming that non–cross‐linked HA can actively remodel the dermal extracellular matrix beyond passive hydration [ 18 ].

By applying the TTZ framework to target the papillary‐to‐upper reticular dermal interface, clinicians may seek to align treatment placement with the proposed biological effects of non–cross‐linked HA formulations, with the aim of supporting dermal hydration and longer‐term tissue quality rather than inducing volumetric change. These findings are consistent with a multicenter randomized controlled trial by Kerscher et al. [ 19 ], which evaluated a cohesive poly‐densified matrix HA‐glycerol formulation. At week 12, aesthetic improvements were observed in 90.7% of the patients, with significantly enhanced skin hydration and effects persisting for up to 9 months.

The application of this framework is particularly relevant for Asian facial morphotypes. As highlighted by regional consensus data, Asian patients frequently prioritize skin texture improvements, such as minimizing pore visibility and improving tone homogeneity, over structural alteration [ 7 ]. Furthermore, Asian morphotypes are often highly susceptible to undesirable volumetric widening when highly cross‐linked fillers are overutilized to address superficial textural concerns [ 20 ]. The thicker and more robust skin structures in the faces of East Asians require deeper filler injections for volumization [ 21 ], which reinforces the importance of stratification. TTZs are intended to target the superficial dermis for improvement of skin quality, a plane distinct from the sub‐superficial musculoaponeurotic system spaces used for volumetric correction [ 21 ]. For Asian patients with isolated textural concerns and no volume deficit, TTZ may offer a volume‐neutral option that avoids the risks associated with superficial placement of cross‐linked fillers. This separation of skin quality‐focusing interventions from volumetric correction could also allow clinicians to address dermal deterioration without risking undesirable volume changes, aligning with the regional preference for more volume‐neutral rejuvenation.

From a technical perspective, the TTZ framework is intended to provide a more structured approach to treatment planning, particularly in historically challenging anatomical regions. Areas such as the periorbital zone and tear trough are complex; indiscriminate superficial injections in these regions frequently result in persistent fluid retention, the Tyndall effect, or surface irregularities due to impaired lymphatic drainage [ 22 , 23 ]. The anatomical zoning utilized in the TTZ framework helps guide the clinician to adjust product distribution, injection depth, and technique based on the specific biomechanical limitations of the zone. This structured approach may support clinical decision‐making and could help reduce the risk of adverse events in delicate areas by prioritizing anatomical knowledge over repetitive technique.

6.1

Limitations and Future Directions

The examples presented here have several limitations. First, they are primarily based on the authors' clinical experience and illustrative cases rather than controlled prospective studies; therefore, the findings are descriptive and are not intended to establish comparative efficacy. The absence of a control group and the lack of blinded evaluation also preclude such comparisons. Furthermore, the selection of cases may introduce single‐center expert practice bias, and the exclusive focus on a specific HA and glycerol formulation results in limited generalizability of product‐specific findings. Further clinical validation is required.

Second, outcome assessment relies largely on qualitative clinical evaluation, including improvements in skin texture, perceived skin brightness, and surface homogeneity. The absence of standardized quantitative measures such as validated skin quality scales, biophysical assessments, or imaging‐based analysis limits objective reproducibility.

Third, although TTZs provide a structured decision‐making framework, treatment outcomes remain dependent on the practitioner. Variability in technique, injection depth, and product distribution may contribute to heterogeneity in real‐world results.

Finally, long‐term durability and optimal maintenance strategies have not been systematically evaluated. The temporal dynamics of treatment response and cumulative effects require further investigation.

At present, TTZ remains a conceptual clinical framework and has not yet been validated as a clinical guideline or standardized treatment algorithm. Future prospective studies should evaluate the validity, reproducibility, and clinical utility of the TTZ framework using standardized assessment methods. Objective skin‐quality measurements could include instrument‐based evaluation of hydration, elasticity, trans‐epidermal water loss, surface topography, pore visibility, and skin reflectance, supplemented by standardized clinical photography and blinded evaluator assessment. Validated clinical rating scales and patient‐reported outcome measures should also be incorporated to assess perceived changes in skin texture, radiance, satisfaction, and treatment acceptability [ 1 , 3 ]. Prospective cohort studies could initially examine within‐patient changes over time, whereas randomized or comparative studies could compare TTZ‐guided treatment with conventional technique‐driven approaches, untreated control areas, or alternative treatment‐planning strategies. Such studies would help determine whether TTZ‐guided planning improves consistency, treatment selection, patient‐reported benefit, and safety across different practitioners, populations, and anatomical zones.

Investigation of TTZ integration in multimodal approaches, such as fillers, threads, and energy‐based devices within the VA methodology, may further enhance treatment precision and outcomes. In addition, emerging digital technologies, including artificial intelligence‐assisted treatment planning, may improve personalization, consistency, and scalability of TTZ‐guided interventions.

7

Conclusion

TTZs are proposed as a potentially reproducible, conceptual, skin quality‐first decision‐making framework within the VA methodology intended to systematize existing clinical principles. By shifting the focus from technique‐dependent application to structured planning, TTZs may offer a scalable and adaptable approach to enhancing skin texture and visual quality, providing a foundation for future clinical and methodological investigation.

Author Contributions

All authors contributed to case collection, data interpretation, manuscript drafting, and critical revision, and approved the final version. All authors take responsibility for the integrity of the work as a whole and have approved this version to be published.

Funding

The authors have nothing to report. No external funding was received for the clinical cases or development of the framework. Medical writing and editorial support were funded by Menarini APAC.

Ethics Statement

This study includes illustrative clinical cases derived from routine aesthetic practice. It does not involve experimental interventions or prospective data collection. All medical procedures described in this report were conducted in accordance with the Declaration of Helsinki.

Consent

Written informed consent was obtained from all patients whose clinical photographs were used.

Conflicts of Interest

V.S. is self‐employed in the Hertitude Clinic, Bangkok, Thailand. H.A. is self‐employed in The H Clinic, Bangkok, Thailand. K.S. is self‐employed in the Face Gallery Clinic, Bangkok, Thailand. V.S. serves as a consultant for A. Menarini (Thailand) and A. Menarini Asia‐Pacific. VA Methodology is an intellectual property belonging to V.S. No logistical or financial support for the execution of this work was received.

临床定位与机制

• 问题起点： 美学医疗的重心正从单纯的容积与轮廓矫正，转向皮肤质量（肤色均匀度、表面均匀度、紧致度、光泽度）这一独立维度；皮肤质量下降可在缺乏明显容积缺损的患者身上独立存在，并独立影响年龄感与满意度。
• 与容积矫正的关系： 容积矫正针对深层（骨骼支撑、脂肪隔室），而皮肤质量干预针对 乳头状真皮与上段网状真皮 ；两者目标不同、不可互换。皮肤菲薄、弹性下降或真皮退变明显者若仅依赖容积矫正，可能需使用过多填充剂，从而增加过度矫正与不自然外观的风险。
• 非交联 HA 的定位： 其会被皮肤内源性透明质酸酶迅速代谢（原文称通常在 1 天内），因此 不提供长期物理结构支撑 ；较持久的获益源于天然生物学反应与水合改善——进入真皮后整合入细胞外基质储水而不增加持续容积，并可能改善成纤维细胞所处环境。
• 甘油的协同作用： 作为经典吸湿剂，甘油在真皮环境内吸引并保留水分、支持表皮屏障、降低经皮水分流失；与非交联 HA 经微针注射共用时协同稳定间质液潴留，形成较持续的水分库。原文引用的体内生物物理评估提示该组合可改善细胞膨压、组织张力与细胞外基质生理环境，从而改善紧致度与抗疲劳性等黏弹特性。
• 双相特性： 既往文献将此类干预描述为「即刻相 + 延迟相」：先为吸湿带来的轻微饱满感，随后转为成纤维细胞机械性激活与胶原刺激的延迟重塑期，恢复弹性与紧致度。

操作要点

• 分区： 框架将面部与颈部划分为额部、颞部、颧部、颧下、颊部、下颌角（jowl）、口周等临床相关区域，各区对应不同的真皮老化模式、生物力学行为与美学意义；框架具弹性，不要求对每位患者全部分区干预。
• 纳入标准： 仅当该区存在局部关注点时，才将其纳入皮肤质量干预的考量——干燥、毛孔粗大、细纹或静态浅表皱纹、表面质地不均（包括萎缩性痤疮瘢痕）、视觉皮肤质量下降；存在上述一项或多项即支持优先处理该区，与容积或结构考量无关。
• 深度： 经皮递送定向于 乳头状真皮—上段网状真皮交界，对应深度约 1 mm ；该层面可接近高密度、代谢活跃的成纤维细胞，同时有助于减少注射过浅造成的表面不规整，以及注射过深带来的容积效应。
• 实施方式： 以点状精准注射将非交联 HA 配方（含甘油者）注入所选靶区，目标是支持水合与质地改善 而不产生容积改变 ；分区选择依据个体患者的主诉、解剖特征与基线皮肤质量，而非预设方案。
• 目标定义： 视觉皮肤质量较高被定义为 表面均匀度改善带来的反射光增加与阴影减少 ，具体表现为毛孔可见度降低、细纹减弱。文中建议未来引入光泽计、反射计或偏振成像等客观工具量化表面反射变化。
• 患者与流程： 原文建议在识别靶区与制定计划前先评估适应证与禁忌证（禁忌情况汇总于原文表1），并按图 2 所列流程完成筛查、靶区选择、治疗与随访。
• 难点区域： 眶周与泪沟解剖复杂，在该区域无差别地进行浅层注射常导致持续性积液、丁达尔效应或因淋巴引流受限造成的表面不平整；分区框架据此引导医师依据各区生物力学限制调整产品分布、注射深度与技术。
• 亚洲人群相关性： 区域共识数据显示亚洲患者更关注毛孔可见度与肤色均匀度等质地问题而非结构改变；亚洲人面部皮肤更厚、更致密，容积矫正通常需 更深 的填充注射，而质地问题若以高交联填充剂浅层处理则易出现非预期的容积增宽——TTZ 提供了一个「容积中性」的浅层选项。

风险与局限

• 作者自述的局限包括：主要基于临床经验与示例病例而非对照前瞻研究； 无对照组、无盲法评估，无法支持比较性疗效结论 ；单中心专家实践偏倚；仅针对特定 HA 与甘油配方，产品特异性结论的外推性有限。
• 结局评估主要依赖定性临床判断（质地、主观亮度、表面均匀度）， 缺乏经验证的皮肤质量量表、生物物理测定与影像分析等标准化定量手段 ，客观可重复性有限。
• 虽提供了结构化的决策框架，但治疗结局仍高度依赖操作者——技术、注射深度与产品分布的差异会造成真实世界结果的异质性。
• 长期耐久性与维持策略尚未系统评估 ；由于非交联 HA 代谢迅速，其效果的维持节奏与累积效应需进一步观察，需按维持性治疗理解。
• 文中引用的成纤维细胞活力提升 15%、I 型胶原基因上调 9.7 倍等数据 来自体外实验 ，与既往 HA-甘油配方第 12 周 90.7% 改善、最长维持 9 个月的数据 均属文献引用 ，构成本框架的机制与文献背景，而非本文验证的在体结果。
• 未来验证路径：前瞻性队列观察个体内随时间变化；随机或对照研究比较 TTZ 引导与传统技术驱动策略、未治疗对照区或其他方案；并纳入客观测量与患者报告结局。