The Evolving Field of Regenerative Aesthetics: A Review and Case Series

Abstract

Dermal fillers such as calcium hydroxyapatite-carboxymethylcellulose (CaHA-CMC), polycaprolactone (PCL), and poly-l-lactic acid (PLLA) are increasingly used as 'biostimulators' to stimulate native collagen production for longer-lasting aesthetic improvement. Volume replacement should, ideally, renew local tissue architectures and functions, but the replaced volume may not align structurally or functionally with the original tissue. The ability to achieve this regenerative, biostimulatory aesthetic rejuvenation requires a thorough understanding of the principles and mechanisms of tissue regeneration and its proper application. We reviewed the concepts of regenerative medicine, regenerative aesthetics, and biostimulation in the context of PLLA and CaHA and discussed the effects on immunological pathways and neocollagenesis when these materials are used as biostimulators in clinical aesthetics. Additionally, to understand how the concept of regenerative aesthetics is applied in the real world, we present cases demonstrating best practices and outcomes when using CaHA-CMC in a group of 11 Asian patients. Asian physicians' practices with CaHA-CMC have evolved beyond its volumizing and contouring benefits to its ability to induce regeneration in aging tissues. This has been achieved through the use of CaHA-CMC as monotherapy or in combination with other modalities. Moreover, CaHA-CMC allows physicians to offer a single, minimally invasive product to patients seeking treatment for skin laxity, wrinkles, crepiness, and volume loss while achieving multiple visible aesthetic improvements. Unlike conventional dermal fillers, the ability to leverage the regenerative qualities of CaHA-CMC effectively resolves age-related aesthetic issues in a durable manner using their body's own systems, allowing patients to emphasize their own unique features.

Keywords: asian; biostimulation; calcium hydroxyapatite; collagen; inflammation; regeneration.

Figure 1. Patient case photographs courtesy of Dr. Stephen Lowe.

A 61-year-old female with neck skin quality concerns due to submental laxity, crepey central anterior neck skin, and horizontal lines is shown before (A) and 12 months after (B) neck treatments. One CaHA-CMC (Radiesse® (Merz North America, Raleigh, NC, USA)) syringe was diluted 1:1 per lower face and delivered by subdermal scraping for biostimulation, or diluted 1:2 to increase CaHA particle diffusion, showing long-lasting, global rejuvenation. Written informed consent to include this image in an open-access article was obtained from the patient. CaHA-CMC: calcium hydroxyapatite-carboxymethylcellulose

Figure 2. Patient case photographs courtesy of Dr. Frank Lin.

Patient shown before (A) and 12 months after (B) treatment. A 42-year-old East Asian female who was very thin, had midface hollowing and significant A-frame deformity and infraorbital hollowing, sought treatment for a tired appearance around the midface and periorbital area. Over two sessions, she received incobotulinumtoxin A (Merz North America, Raleigh, NC, USA) for the masseter and diluted CaHA-CMC for temple contouring and submalar depressions, as well as a CaHA-CMC diluted 1:2 as a mid-cheek pan-facial wash. Undiluted or minimally diluted CaHA-CMC was also placed in the chin and deep pyriform fossa, while hyaluronic acid (Merz North America, Raleigh, NC, USA) was applied to the A-frame and tear trough area. Written informed consent to include this image in an open-access article was obtained from the patient. CaHA-CMC: calcium hydroxyapatite-carboxymethylcellulose

Figure 3. Patient case photographs courtesy of Dr. Indra Lesthari.

Patient shown before (A) and at one-year follow-up (B). The patient was a 42-year-old female who requested fillers for aging skin and to improve the midface, lower face, and submental sagging. For cheek augmentation or contouring, undiluted CaHA-CMC with lidocaine was injected deep under the muscle and over the bone in the mid-zygoma (three boluses of 0.05 mL each, in three lines). For the nasolabial folds, two boluses of 0.05 mL each were placed in the subcutaneous layer. One bolus (0.1 mL) was placed deep beneath the mid-cheek muscle, with 0.01-0.05 mL placed slightly subcutaneously for contouring and to pull the skin medially. The remaining undiluted CaHA with lidocaine (up to 0.05 mL) was spread in a thin subcutaneous layer up to the preauricular layer. One syringe of CaHA-CMC was diluted 1:1 and spread to other facial areas, including the upper eyebrow and temple, to tighten the skin and subcutaneous fat, but not to volumize the area, while one syringe of CaHA-CMC (diluted 1:2) was used for submental and neck biostimulation. Written informed consent to include this image in an open-access article was obtained from the patient. CaHA-CMC: calcium hydroxyapatite-carboxymethylcellulose

Figure 4. Patient case photographs courtesy of Dr. Beverly Ong Amoranto.

A 30-year-old male patient was treated for rolling and boxcar acne scars, shown before (A) and at four months (B) post-treatment with one syringe of hyperdiluted CaHA-CMC (1:2 dilution). Written informed consent to include this image in an open-access article was obtained from the patient. CaHA-CMC: calcium hydroxyapatite-carboxymethylcellulose

Figure 5. Three patients' photographs courtesy of Dr. Ho Sung Choi.

All patients were shown before and three months after treatment. A, B: A 62-year-old female received a 1:1 dilution of CaHA-CMC in the perioral area, followed by undiluted CaHA-CMC (0.3-0.5 mL) for perioral accordion lines. Fine lines on the perioral surface were treated with hyaluronic acid. C, D: A 64-year-old female with neck skin laxity and necklines received two syringes of CaHA-CMC (1:2 dilution) injected slowly and evenly via four to five neck entry points per neck side. E, F: A 72-year-old female patient is shown before and three months after neck rejuvenation. CaHA-CMC (1:2 dilution) was delivered through four to five entry points per neck side through a 23G cannula traveling in the superficial (subdermal) plane and placed in boluses up to 0.02 cc for even distribution. CaHA-CMC: calcium hydroxyapatite-carboxymethylcellulose

Figure 6. Patient case photographs courtesy of Dr. Tuck Wah Siew.

A 58-year-old female with ptosis (jowls), skin laxity and textural abnormalities, facial volume loss, and dyschromia before (A) treatment and three months after receiving a total of 775 MFU-V lines delivered with a 1.5 mm transducer (B), showing visible lifting. Diluted CaHA-CMC (one syringe) was also injected at three months. At a further three months post-CaHA-CMC (C), additional CaHA-CMC and MFU-V-associated lifting and improvements were visible. Written informed consent to include this image in an open-access article was obtained from the patient. CaHA-CMC: calcium hydroxyapatite-carboxymethylcellulose; MFU-V: microfocused ultrasound with visualisation

Figure 7. Patient case photographs courtesy of Dr. Yui Lam.

A 42-year-old lady received a total of 215 lines of Ultherapy, with a 1.5 mm transducer, followed by 1.5 mL of CaHA-CMC (1:2) evenly spread across the skin, and is shown at baseline (A), one (B), and six months (C) post-treatment for skin quality improvements. Written informed consent to include this image in an open-access article was obtained from the patient. CaHA-CMC: calcium hydroxyapatite-carboxymethylcellulose