<p>Hydroxyapatite Particles Induced Modulation of Collagen Expression and Secretion in Primary Human Dermal Fibroblasts</p>

Abstract

Background Hydroxyapatite (HA) [Ca 5 (PO4) 3 (OH)] is a naturally occurring calcium phosphate which makes up 60–70% of the dry weight of human bones. Nano-scale HA particles are increasingly being used as carriers for controlled and targeted delivery of bioactive agents like drugs, proteins, and nucleic acids due to their high porosity, negative charge, and biodegradability. Purpose Although much effort has been devoted to understanding the delivery kinetics and effects of the payloads in such carriers, a thorough understanding of the influence of the carriers themselves is lacking. Methods HA particles (300 µg/mL) were administered to primary human dermal fibroblasts (HDFs). The uptake and intracellular localization of the particles were determined by flow cytometry, confocal imaging, and transmission electron microscopy (TEM). Immunological assays and PCR were performed to determine the levels of pro-inflammatory cytokines and collagens in cell lysates and media supernatant. Results The current study explores the effects of poly-dispersed HA particles on primary HDFs as a model system. The majority of the particles were determined to range between 150 and 200 nm in diameter. Upon exposure to HA suspensions, primary HDFs internalized the particles by endocytosis within 6 hours of exposure, showing maximum uptake at 72 hours following which the particles were exocytosed by 168 hours. This correlated to reduced secretion of various pro-inflammatory and pro-collagenic cytokines. Biochemical analysis further revealed a reduction in Type I collagen expression and secretion. Conclusion HA particles have an immune-modulatory effect on dermal fibroblasts and reduce collagen production, which may impact the integrity of the extracellular matrix (ECM). This study demonstrates the need to consider the secondary effects of particulate carriers like HA, beyond basic cytotoxicity, in the specific tissue environment where the intended function is to be realized.

An update on hydroxyapatite/collagen composites: What is there left to say about these bioinspired materials?

“…Although hard tissue engineering is always inherent to HAp/collagen composites, it is important to explore the generated know‐how so far and reflect on its usefulness in other areas of biomedicine. Recent studies applied these biomaterials for skin tissue engineering, showing its potential to be used either as cell transplantation scaffold for skin wound regeneration or as wound dressing material in plastic surgery, burns treatment or skin diseases 116,117 . According to the study of Ribeiro et al 116 calcium ions provided by nano‐HAp enhanced cellular growth and proliferation rates and prevented adhesion of pathogenic bacteria strains typically found in human skin flora 116 .…”

“…In fact, calcium has an important role in maintaining homeostasis in mammalian skin, promoting wound healing 118,119 and thus calcium phosphate‐based materials can be reinvented for skin regeneration. However, other study points out that prolonged cell exposure to HAp particles can reduce the transcriptional expression, translation, and secretion of collagen, which could compromise the integrity of the extracellular matrix (ECM) 117 . In this way, it is necessary to complement different factors, mainly related to the properties of the HAp used.…”

“…Recent studies applied these biomaterials for skin tissue engineering, showing its potential to be used either as cell transplantation scaffold for skin wound regeneration or as wound dressing material in plastic surgery, burns treatment or skin diseases. 116,117 According to the study of Ribeiro et al 116 calcium ions provided by nano-HAp enhanced cellular growth and proliferation rates and prevented adhesion of pathogenic bacteria strains typically found in human skin flora. 116 In fact, calcium has an important role in maintaining homeostasis in mammalian skin, promoting wound healing 118,119 and thus calcium phosphate-based materials can be reinvented for skin regeneration.…”

“…However, other study points out that prolonged cell exposure to HAp particles can reduce the transcriptional expression, translation, and secretion of collagen, which could compromise the integrity of the extracellular matrix (ECM). 117 In this way, it is necessary to complement different factors, mainly related to the properties of the HAp used.…”

One-Step Synthesis of Magnetic Nanocomposite with Embedded Biologically Active Substance

“…Enhancing HAP with magnetic NPs is promising for a number of procedures, including the treatment of microtrauma and other injuries, pro-osteogenic and pro-angiogenic activities [ 11 ], the printing of biologically compatible matrices for biomedical applications [ 12 ], carrying anticancer drugs [ 13 ], performing hyperthermia treatments [ 14 ], and resonance imaging. HAP/magnetic NP composites are promising biomaterials for targeted drug delivery systems [ 15 ], for example, for orthopedic drugs, and the protein adsorption/controlled pH-dependent release of antitumor drugs [ 16 , 17 , 18 ]. New areas of potential application are gene therapy [ 19 , 20 ], antibacterial nanocomposites, and composites for implants [ 21 ].…”