Regenerative aesthetics aims to restore the structure and function of aging skin. Two products, Radiesse (CaHA) and NCTF 135 HA (micronutrient mesotherapy) have been established as minimally invasive treatments that restore the structure and function of various skin components. It has been anecdotally observed by the authors, however, that some patients respond suboptimally to regenerative treatments without a clear indication as to why. It was hypothesized that micronutrient deficiencies in some patients may contribute to their lack of responsiveness and that a concurrent delivery of amino acids and co-enzymes may create a nutritional reservoir necessary for optimal protein synthesis. Noting that CaHA is known to drive the regeneration of extracellular matrix proteins, the aim of this case series was to investigate if “priming” the skin with NCTF 135 HA could lead to enhanced clinical effects of CaHA. The combination treatment resulted in improvements in panfacial aesthetics, skin laxity, wrinkle severity, skin luminosity, hyperpigmentation, and in skin and subcutis thicknesses in 100% of patients following a single treatment. This study is the first to introduce skin priming via diluting a regenerative biostimulator treatment with an amino acid-based diluent.  Citation: Theodorakopoulou  E, McCarthy A, Perico V, et al. Optimizing skin regenerative response to calcium hydroxylapatite microspheres via poly-micronutrient priming. J Drugs Dermatol. 2023;22(9):925-934. doi:10.36849/JDD.7405.