Comparative Effects of Injectable Biostimulatory Agents (Calcium Hydroxyapatite, New Cellular Treatment Factor, VAMP, and Human Exosomes) and Their Combination on Skin Regeneration.

BACKGROUND

Injectable biostimulatory and bioactive agents are increasingly used to enhance dermal regeneration and improve skin quality. Polydeoxyribonucleotide (PDRN), polyrevitalizing multicomponent solutions, calcium hydroxylapatite microspheres, and human-derived exosomes have been proposed to stimulate fibroblast activity, collagen remodeling, and angiogenesis. However, direct comparative evidence in intact skin remains limited.

OBJECTIVES

The aim of this study was to compare the histological and angiogenic effects of PDRN, polyrevitalizing solutions, calcium hydroxylapatite, human-derived exosomes, and their combination on dermal regeneration in intact skin using a hamster model.

METHODS

One hundred and sixty-eight adult Syrian hamsters were randomized into 7 groups (n = 24/group): untreated control, saline control, polyrevitalizing solution, PDRN, exosomes, calcium hydroxylapatite, and combination therapy. All treatments were administered subcutaneously (0.1 mL per site). Skin samples were collected at days 3, 7, and 14 (n = 8/group/time point). Histological evaluation included hematoxylin-eosin, Masson's trichrome, and Van Gieson staining to assess dermal architecture and collagen organization. Angiogenesis was quantified using CD34 immunohistochemistry and microvessel density analysis.

RESULTS

All active treatments increased dermal cellularity, collagen deposition, and microvessel density compared with control and saline groups. Combination therapy produced the greatest enhancements in collagen fiber density, organization, and angiogenesis, with significantly higher CD34-positive microvessel density at days 7 and 14 (P < .05 vs all single-agent groups). Among single agents, the polyrevitalizing solution (new cellular treatment factor) demonstrated the most pronounced overall regenerative response, followed by VAMP (PDRN), Radiesse, and adipose stem cell exosomes.

CONCLUSIONS

Injectable bioactive and biostimulatory agents enhance dermal remodeling and neovascularization in intact skin, with combination therapy targeting complementary regenerative pathways yielding the most pronounced histological effects. These findings support multimodal injectable strategies for skin rejuvenation and regenerative dermatology.