Is the Foundation of Regenerative Orthobiologics and Aesthetics Built on Mechanistic Manipulation?

Abstract

Scott M. Martin*

Orthobiologic and aesthetic biostimulatory injectables hold a privileged regulatory and commercial position in the orthobiologic and aesthetic injectable markets. Most common amongst these injectable products are Platelet-Rich Plasma (PRP), Bone Marrow Aspirate Concentrate (BMAC), Calcium Hydroxylapatite (CaHA; Radiesse®), and Poly-L-Lactic Acid (PLLA; Sculptra®). Currently, PRP qualifies for Investigational New Drug (IND)-exempt Randomized Controlled Trial (RCT) access as a minimally manipulated, homologous-use autologous biologic. CaHA and PLLA have received FDA clearance for aesthetic applications largely due to mechanistic claims of neocollagenesis and fibroblast biostimulation. BMAC has widespread off-label clinical usage due to clinical literature claims of mechanistic growth-factor and mesenchymal stem cell presence. The purpose of this perspective review is to highlight a foundational mechanistic attribution error in the previous clinical literature of these four orthobiologic and aesthetic injectables. The previous in vitro findings that claimed proliferative, chondrogenic, and neocollagenic effects of these injectables incorporated Fetal Bovine Serum (FBS) or fetal calf serum into the cell culture models. FBS does not have a functional analog in human synovial fluid, bone marrow, or dermal interstitium and is not commercially available to clinicians as an injectable product. The reagent largely responsible for the mechanistic signal produced in these previously conducted clinical trials is absent from clinical practice and cannot be replicated in human patients. Burgeoning state regulatory frameworks around which new Stem Cell and Regenerative Therapy Laws are drafted should therefore anticipate and invite both comparative IRB-approved research and expanded clinical use as paired conditions of the same legislative authority.

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