Smart PDOs™ and the Cartesian Technique™: A milestone in facial rejuvenation with bioactive scaffolds

Hypothesis

“The implantation of enriched polydioxanone sutures smart polydioxanone suture (Smart PDOs™) following a vector order of forces in a facial Cartesian tracing (the Cartesian Technique™), will improve the clinical performance of the sutures and optimize the results of the treatment of rhytides and skin deflation.”

Preclinical trials : Development of smart PDOs™

To verify the feasibility of polydioxanone sutures as scaffolds for the controlled release of cosmeceutical drugs, preclinical laboratory tests were performed by subjecting PDO sutures to capillarity, biodegradation, and controlled release tests.

PDO sutures used in facial tightening are known to be polymeric biomaterials that slowly biodegrade through hydrolysis (cite article biodegradation). That is why, before proposing their use as bioactive scaffolds for controlled release, it had verified whether the suture had the capillarity to be enriched with cosmeceutical active ingredients, that is, the ability to hold liquid substances in its structure without said wetting producing biodegradation immediate of the PDO suture.

To do this, we started with the instrumental analysis of the PDO suture impregnated with the active ingredient, evaluating the absorption of fluids by observation by optical microscopy and scanning electron microscopy (SEM). Controlled release analyzed by ultraviolet-visible (UV-vis) spectroscopy.

Optical microscope observation

At the end of the evaluation period (24, 48, and 72 h after immersion), the PDO suture segments were placed on slides and observed under a Nikon® reflection optical microscope at ×4 and ×10.

Scanning electron microscopy (SEM)

The PDO suture embedded with Arg for 1 min, after drying in the environment, was fixed with a 3:3 mixture at 4°C, for 24 h for SEM observation (3% formaldehyde + 3% glutaraldehyde in 0.1 M cacodylate buffer), pH6.3. Subsequently, the alcoholic dehydration, desiccation, and metallization of the samples were carried out for observation under a scanning electron microscope (Hitachi S-2500).

CSi release rate from PDO

The PDO thread with Organic Silicon (CSi) and the PDO suture without medication were analyzed in a UV-vis spectrophotometer to determine their controlled release capacity and to detect if there is degradation or loss of thread mass.

The prolonged release of the drug was assessed by recording the rate of release of CSi from the PDO suture and, a curve of concentration released over time (at 5, 15, 30, 60, and 2400 min or 24 h) was constructed.

Design of the “the Cartesian Technique™” protocol

During facial aging, two major phenomena contribute to the loss of firmness of the soft tissues of the face: lipomatosis and deflation. Lipomatosis refers to the increase in facial volumetric weight due to fat infiltration in adipose compartments of the middle and lower third of the face. Deflation refers to skin flaccidity or laxity in which the skin results and falls forming deep furrows and causing loss of mandibular contour.⁷

The Cartesian Technique™ clinical protocol is a set of facial lifting techniques designed from the application of spatial geometry to the face, which is part of our paradigm called facial morpho geometric analysis.⁸

The theory that underlies the Cartesian Technique™ implies that to achieve a more effective tightening of the aged face, before intervening with facial support sutures, dermal repositioning must be planned. This plan is based on a logical system of redistribution of forces, which allows for optimizing the results of a facelift with threads while improving the clinical performance of the suture with the use of Smart PDOs™.

Our theory proposes that there are unalterable or visually easy to locate craniometric points, known as anthropometric landmarks [Figure 1], which are useful for locating and tracing horizontal and vertical planes. The following points are considered anthropometric milestones: Trichion, glabella, nasion, endocanthon and exocanthon (internal and external canthus, which form the ocular intercanthal plane), pupillary, infraorbital, subnasal, stomion (between the upper and lower lip, through which the bicommissural plane is drawn) pupillary, infraorbital, subnasal, stomion (between the upper and lower lip, through which the bicommissural plane is drawn), gnathic (or mental point) and gonion (at the level of the gonial angle of the mandible).”

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Figure 1:

Referential anatomical landmarks for drawing Cartesian planes.

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These points, when connected, become vertical and horizontal planes. The line that joins the milestones from trichion to gnathion (vertical) divides the face into two halves (right and left), similar to the vertical line or Y-axis in a Cartesian plane, which we call the sagittal plane of the face or facial midline.

In the horizontal sense, from the union of the infraorbital anthropometric points (or infraorbital foramen) and the porion (highest point of the external auditory canal), the layout of a straight line is derived, called the “X axis”, which is the transverse or midfacial plane [Figure 2]. This X plane cuts perpendicular to the facial midline or Y-axis, coinciding with the well-known Frankfort cephalometric plane (projection of an imaginary line that starts from the tragus of the ears passing at the level of the cheekbones to join in the center). The crossing or point where the vertical line and the horizontal line intersect perpendicularly is known in Cartesian terms as the zero point or origin of the lines.

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Figure 2:

Cartesian planes applied to the face.

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Likewise, the tracing of vertical lines from the endocanthion and exocanthion (inner and outer edge of the eyes) generates four columns or spaces called vertical planes. The central plane (Pc) of the face, or “central facial column”, between the inner edges of the inner corners of the eyes. On each side in parallel, the column between the internal canthal and pupillary midline is the internal canthal plane (Pci).

The space from the pupillary point to the external canthal is known as the median canthal plane (Pcm) and the outermost from the external edge to the tragus area of the ear, the external canthal plane (Pce), which is the most stable area of the face despite aging, so it is an area of fixation and traction par excellence [Figure 3].

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Figure 3:

Vertical Cartesian planes of the face.

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In the same way, in the frontal position horizontally, other important planes are generated [Figure 4] that also intersect the vertical planes:

• Frontal plane (Pf) or space between Trichion and glabella;

• Superior ocular plane (Pos) between glabellar and interpupillary;

• Inferior ocular plane (Poi) between the interpupillary and infraorbital lines;

• Nasal oculus plane (Pon) between infraorbital and subnasal;

• Nasolabial plane (Pnl) between subnasal and commissural;

• Labio-mental (Plm) between commissural and mental.

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Figure 4:

Construction of horizontal planes in frontal position.

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In this way, the intersection of these horizontal and vertical lines converts the face into a squared canvas which, in itself, is a spatial coordinate system, useful for orienting an effective dermo-support [Figure 5]. Within this coordinate system, more Cartesian planes form new zero points in each of the resulting sections, thus giving the possibility of creating a vector system of threads PDO scaffolding.

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Figure 5:

Horizontal Cartesian planes of the face. Fp: Frontal plane, SOp: Superior ocular plane, IOp: Interior Ocular Plane, NOp: Nasal oculus plane, NLp: Nasolabial plane, LMp: Labio-mental plane.

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According to the Cartesian Technique™, the PDO sutures should be positioned as vectors between each quadrant, in an upward oblique direction, which will allow the suture thread to provide a sustaining force with a coherent vector sense, direction, and magnitude, thus generating scaffolding forces with sufficient anchorage to produce greater facial tension, which optimizes the polydioxanone thread insertion technique. The arrangement of the PDO threads in diagonal vectors to the Cartesian system is illustrated below:

1. The white drop of material represents the zero point or origin of the Cartesian planes, which must be crossed by the PDO suture (orange thread) in an ascending oblique direction as vectors toward the external canthal plane and toward the internal canthal plane, forming a mesh that constitutes a vectorial scaffolding system for the polydioxanone threads [Figure 6a].

2. In turn, with the Cartesian Technique™, at least, three internal vectors could be designed for this sectorization in each grid, using active ingredients such as liquid PDO to reinforce the facelift [Figure 6b].

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Figure 6:

(a) and (b) Cadaveric configuration for the Cartesian Technique™.

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Clinical trial

A homogeneous sample of 35 patients was studied, obtained under randomization, without a control group, with the following diagnoses in common: primary and secondary rhytides, grade I lipomatosis, and grade I deflation. After completing the clinical history and informed consent, the patients were photographed and treated with the Cartesian Technique™ implanting polydioxanone sutures on both sides of the face.

The arrangement of the PDO sutures is carried out following the logic of vectorial support, in which the lines of greatest traction force are obtained by intersecting the Cartesian planes traced on the face (the Cartesian Technique™).

There are no exit points, only the entry orifice, since this same port is where the cannula emerges, leaving the monofilament on the skin plane after its exit. The thread applied into the superficial muscular aponeurotic system (SMAS), but the extreme of the thread, has not tied at the end.

The insertion of the threads will always be where the Cartesian planes intersect, forming the zero point, with vector magnitudes always directed cranially.

The yellow lines are the Cartesian planes; the green lines represent the scaffolded sutures.

The circle at the beginning of the arrows indicates the entry hole of the cannula with the thread.

The arrowhead indicates the direction of thread insertion [Figure 7].

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Figure 7:

Face paint illustrating the Smart Polydioxanone Suture (Smart PDOs™) vector scaffolding system. The black arrows indicate the direction in which the threads are inserted to obtain the maximum upward vector force., in an oblique direction towards the “zero” point, that is, towards the place of confluence of forces (crossing of horizontal, vertical and oblique lines) in the Cartesian coordinate plane

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In each green line, a PDO number 27 G suture was inserted, motivated by the fact that it is a needle that allows an intradermal and subcutaneous application, even better redirecting the thread system and at the same time facilitating a better dosage of the cosmeceutical product used to enrich the thread (organic silicon).

To increase suture performance, the bioactive scaffolding technique was performed with Smart PDOs™. For this, organic silicon is incorporated into each thread at a dose of 0.1 mL, so with this technique, it is necessary to use 1 mL syringes with an interchangeable needle, which must be placed at the base of the needle or its pivot before withdrawing the thread to deliver the active ingredient through the cannula.

The evaluation of the tightening effect was carried out using clinical photographs immediately after the insertion of the sutures, 8 and 15 days later. In the photos, skin parameters of turgor, elimination of wrinkles (rhytids) and skin tightening were evaluated.

Clinical examination of the elastic resilience of the skin was then performed by the traditional method for the pinch test of skin turgor. A photographic record of the brightness or hydration of the skin was also carried out.

Based on previous methods, skin turgor assessment was finally classified on a visual turgor recovery scale whose values were: 0 = undetectable, 1 = low, 2 = moderate, and 3 = high.

On the other hand, to measure the position of flaccid or deflated tissues, the other scale used was the deflation scale (created by the authors⁸) which consists of:

“The level of deflation was measured with the vertical dimension scale [Figure 8]. The vertical dimension is the distance from the base of the nose to the chin. This distance must be compared with the distance from the tragus of the ear to the external canthus of the eye, which must be the same. This measurement is stable and therefore valid to verify if the lifting with threads or any other technique successfully achieves the replacement of the tissues.”⁸

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Figure 8:

Method for measurement of the esthetics vertical dimension.

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Depending on the difference in millimeters that exists between these two distances (tragus-singing vs. nose-chin) a classification of the levels of descent, deflation, or sagging of the tissues was established [Figure 9]: Mild = difference between 2 and 5 mm, moderate: ≠ 7–10 mm, and severe: ≠ 10 mm.

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Figure 9:

Levels of loss of aesthetic vertical dimension (AVD) by descent of the aging tissues.

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Based on this classification based on the loss of the esthetic vertical dimension, another scale was established to classify said deflation or severity of tissue sagging into three levels [Figure 10] that can be detected at the level of the facial contour by drawing a tangent line to the mandibular edge:

1. Grade 1 deflation: A discrete excess of the tissues below the mandibular line and corresponds to the level of slight descent (Decrease in Aesthetic Vertical Dimension (AVD) : ≠ 2–5 mm)

2. Degree 2 deflation: Deflation, moderate slump whose exceedance is proportional to the decrease in AVD moderate level (: ≠ 7–10 mm)

3. Grade 3 deflation: Severe sagging, mobile skin folding, with the collapse of the tissues of the mandibular area toward other tissues of the neck.

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Figure 10:

Deflation scale by facial aging.

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Said scales have been endorsed by the authors of this manuscript, which can be consulted in Velazco de Maldonado et al.⁸

The degree of recovery was clinically evaluated by three observers, specialists in dermatology, facial esthetics, and a plastic surgeon. The degree of satisfaction with the treatment was reported based on medical judgment, as shown in Table 1.

Table 1: Clinical evaluation of the cutaneous effect of the Cartesian Technique™ with Smart PDOs™.

	Before	Immediate	8 days	15 days
Turgor	Short 100%	High 100%	High 100%	High 90%
Rhytides	Accentuated 100%	Reversal of furrows and rhytides 100%	Reversal of furrows and rhytides 100%	Reversal of rhytides, smoothing of deep grooves 80%
Face tightening	Grade I deflation 100%	No deflation 100%	No deflation 100%	No deflation 90%

Smart PDOs™: Smart polydioxanone suture

Capillarity test versus suture degradation with the technique Smart PDOs™

Optical microphotographs at 24, 48, and 72 h [Figure 11] show structural changes in the fibers of the PDO threads. The capillarity phenomenon is observed as a swelling in the yarn (retention of an aqueous content between the peripheral layers and the central core of the thread) accompanied by an increase in the interlaminar spaces (whitish stripes), indicative of the hygroscopic phenomenon experienced by the presence of organic silicon in the fiber.

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Figure 11:

Polydioxanone (PDO) thread after 24, 48, and 72 h of immersion in organic silicon. (a) ×4. The central area of the thread is surrounded by light-dark areas due to the retention of the drug. (b) ×10. An increase in interfibrillar and interlaminar spaces corresponds to the phenomenon of fluid absorption or capillarity of the PDO.

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Sem

The smooth PDO threads are observed as cylinders with cuts on their periphery in the form of micro-spicules in opposite directions, which is possibly part of the factory design for their micro-anchoring [Figure 12a].

The silicon covers the thread and interpenetrates the fiber slit, demonstrating the indemnity of the PDO thread as it is enriched with CSi, which does not alter the structure of the thread, nor does it hydrolyze it, so it is presumed that the PDO thread with CSi is a scaffold physically stable [Figure 12b].

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Figure 12:

(a) Topography of the polydioxanone (PDO) thread without the drug (control) scanning electron microscopy (SEM) microphotograph at ×25. Spicular slits are observed on the lateral edges. (b) PDO thread with Arg. SEM microphotograph at ×150. A layer covers the wire and interpenetrates the fiber cleft corresponding to the silicon on the PDO surface.

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Controlled release of silicon from the PDO suture

Graph 1 evidences the UV-Vis spectrum of silicon release from PDO as a function of time. It can seem that at 24 h (pink) the highest absorbance peak is generated, this could correspond to an abrupt release of a large part of the drug into the medium, possibly due to partial and superficial degradation of the scaffold releasing the silicon into the medium. Graph 2 shows a slope in the form of a curve, one order higher than the zero-order, which indicates that it could be a first-order reaction; therefore, the release kinetics of silicon from PDO obey a controlled release system.

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Graph 1:

Ultraviolet-visible spectrum of the polydioxanone (PDO) at the time intervals in which the release of organic silicon was measured. C-Si: Organic Silicon

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Graph 2:

Release curve of Organic Silicon (C-Si) from the Polydioxanone (PDO) thread plotting the absorbance as a function of time.

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Histopathology study

The technique of enriching PDO threads with active ingredients such as organic silicon was previously studied through preclinical laboratory tests, subjecting PDO sutures to capillarity, biodegradation, and controlled release tests. In addition, the enriched sutures were tested on the skin of Wistar rats in the facilities of the Animal Experimentation Biotery of the Universidad de los Andes, before project approval by the bioethics committee of the same university with endorsement number CEBIOULA N123 of July 22, 2019.

For this reason, given the biocompatibility that has already been scientifically supported for the use of PDO sutures in humans and active ingredients such as organic silicon, the bioethics committee did not consider it necessary to carry out a histopathological study in humans. Although it was not the intention of the team of authors of this manuscript to include all the results of said histopathological study, for reasons of length of the text, we included some representative images of the tissue changes observed in the dermis and epidermis of rats with this technique.

Thirteen rats from the BIOU line: Wistar were divided into a control- control group (3) and an experimental group PDO-Silicon (5), a control group PDO alone (5), to which treatment was administered intradermally on the back. Euthanasia was performed at 4 weeks; skin samples were fixed in 12% formalin for further histological analysis [Figure 13].

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Figure 13:

Skin samples.

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The observed results revealed characteristics similar to the young skin indicated in the control-control group [Figure 14]. The experimental group treated with the enriched suture technique showed the absence of inflammatory infiltrate and few blood vessels (100%) [Figure 15 and 16], few hair follicles (60%) [Similar to those observed in Figure 14], dense connective tissue (100%) with thick, intertwined collagenous fibers (100%) [Figure 17], no intercellular edema (100%), high fibroblast cellularity (100%) [Figure 18], thin epidermis with rectified basement membrane (60%) [Figure 19], and high dermal thickness (80%) [Figure 20]. It concluded that silicon synergistically potentiated the tissue effect of the PDO suture, generating greater biostimulation of fibroblasts with better quality collagen fibers, greater restructuring and redensification of the skin, and avoiding the late inflammatory response.

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Figure 14:

Microphotograph of a histological section of the skin control-control group of the BIOU line: The stratum corneum is identified (the black arrows at the top of the histological preparation indicate the purple band corresponding to the stratum corneum) with its scaly cells (translucent strand located on the purple band or stratum corneum, layer indicated with black arrows), fibroblasts (white arrows indicating purple nuclei of fibroblasts in the dermis), pilosebaceous units in the dermis (yellow arrow on the right margin) and a follicle in the background behind the epidermis (yellow arrow in the purple stratum, above).

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Figure 15:

Histological section micrograph of hematoxylin and eosin-stained skin (×40). A typical image of scant and perivascular inflammatory infiltrate (circle) was observed. Indicative that it is a mild, physiological inflammatory response, more typical of tissue biostimulation.

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Figure 16:

Photomicrograph hematoxylin and eosin-stained histological section of skin (×40) representative of dense avascular connective tissue and absence of inflammatory infiltrate in the experimental group.

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Figure 17:

Photomicrograph hematoxylin and eosin-stained histological section of skin (×40) representative of the dense connective tissue observed detailing the thickness and organization of the collagen fibers. The circle indicates the point from where the cannula should be accessed. From the same opening hole in the skin you can enter in several directions as indicated by the 3 oblique black arrows.

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Figure 18:

Photomicrograph hematoxylin and eosin-stained histological section of skin (×40). Elevated fibroblast cellularity was observed in the experimental group.

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Figure 19:

Photomicrograph hematoxylin and eosin-stained histological section of skin (×10). The dotted black line borders the shape of the basement membrane that has been rectified by the thick epidermal thickness in the experimental group

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Figure 20:

Photomicrograph hematoxylin and eosin-stained histological section of skin (×40). The oblique black arrow crossing the histological preparation shows the size or thickness of the dermis in the experimental group (it occupies 4/4 of the field).

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Results of the clinical trial

None of the patients reported any secondary and/or adverse effects and no adverse events were observed in the follow-up reviews.

A panel of three expert observers performed the clinical and photographic assessment. The expert operator who performed the treatments did not participate, to avoid interpretation bias. Facial tightening is an indirect measure obtained by contrasting the distances between the facial thirds before and after the lift, considering that a good lifting effect is achieved when the tissues are repositioned to the point that the proportion is similar between the three-thirds of the face [Figures 21-27].

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Figure 21:

Case 1. Facial firming was obtained with the Cartesian Technique™ and smart polydioxanone suture (Smart PDOs™).

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Figure 22:

Case 2 - (a) Diagram of design of the Cartesian Technique™ and smart polydioxanone suture (Smart PDOs™) over the patient. The yellow arrows indicate the direction of the Polydioxanone (PDO) thread (vector). As indicated by the 2 yellow arrows, 2 PDO sutures were inserted between the infraorbital and subnasal plane. Between the infraorbital and subnasal plane, 3 vectors or threads were inserted (yellow arrows) and 3 vectors (in the direction of the yellow arrows) or 3 threads were inserted between the planes of the lower third of the face: from subnasal to commissural or stomion and from commissural to mental. (b) Before and (c) after. (d) Results of the Cartesian Technique™ and Smart PDOs™.

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Figure 23:

Case 3 – (a) Diagram of design of the Cartesian Technique™ and smart polydioxanone suture (Smart PDOs™) over the patient. (b) Before and (c) after. The white arrows in (a), (b), and (c) indicate how by elevating the most superior and external tissues of the face with this system, the nasolabial fold, nasojugal fold, mentolabial folds, and primary and secondary wrinkles are reversed. The Jowls is also softened, demarcating the mandibular contour. (d) Results of the Cartesian Technique™ and Smart PDOs™. The horizontal and vertical dotted line represents the transverse plane of the face or X axis and the Y axis of the face. The dotted dividing line shows the untreated sagging tissues on the left side of the face, whereas, the tissues on the right side of the face (treated with the Cartesian technique and Smart PDOs) are observed to be much higher.

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Figure 24:

Case 4: Diagram of design of the Cartesian Technique™ and smart polydioxanone suture (Smart PDOs™) over the patient and its results. The white arrows indicate how by elevating the most superior and external tissues of the face with this system, the nasolabial fold, nasojugal fold, mentolabial folds, and primary and secondary wrinkles are reversed. The Jowls are also softened, demarcating the mandibular contour.

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Figure 25:

Case 5: Diagram of design of the Cartesian Technique™ and smart polydioxanone suture (Smart PDOs™) and its results. The white arrows indicate how by elevating the most superior and external tissues of the face with this system, grooves such as the nasolabial groove are reversed.

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Figure 26:

Case 6: Diagram of design of the Cartesian Technique™ and smart polydioxanone suture (Smart PDOs™) and its results. The white arrows indicate how by elevating the most superior and external tissues of the face with this system, furrows such as the nasolabial groove are reversed.

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Figure 27:

Case 7: Diagram of design of the Cartesian Technique™ and smart polydioxanone suture (Smart PDOs™) and its results. The white arrows indicate how by elevating the most superior and external tissues of the face with this system, furrows such as the nasolabial groove are reversed.

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The Cartesian scaffold managed to reverse deep grooves, even in problematic areas such as the malar festoon and nasojugal groove.

It softened the Nasogenian Groove and mentolabial folds and the primary and secondary rhytides.

It opens the ocular expression and densifies the skin of the entire face, but the tension achieved in the frontal and superciliary area counteracted the upper blepharochalasis. Dermo sustentation also manages to demarcate the Mandibular contour, hiding the Jowls.

Follow-up period

Long-term follow-up was performed at 2 and 4 months after the placement of the threads [Figure 28]. No follow-up was carried out at 6 months, since, at 180 days, the PDO has already been completely reabsorbed according to the indications of the manufacturers and preclinical studies.

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Figure 28:

Results of the follow-up period. The white arrows indicate how tissue elevation is maintained with this system up to 4 months later.

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