No abstract

The monocyte-derived macrophage (MDM), present at biomaterial implantations, can increase, decrease or redirect the inflammatory and subsequent wound healing process associated with the presence of a biomaterial. Understanding MDM responses to biomaterials is important for improved prediction and design of biomaterials for tissue engineering. This study analyzed the direct differentiation of monocytes on intact, native collagen. Human monocytes were differentiated on decellularized bovine pericardium (DBP), polydimethylsiloxane (PDMS) or polystyrene (TCPS) for 14 d. MDMs on all surfaces released high amounts of MMP-9 compared to MMP-2 and relatively little MMP-1. MDMs differentiated on DBP released more MMP-2, but less acid phosphatase activity. MDMs on all three surfaces released low amounts of cytokines, although substrate differences were found: MDMs on DBP released higher amounts of IL-6, IL-8, and MCP-1 but lower amounts of IL-10 and IL-1ra. This research provides evidence that MDMs on decellularized matrices may not be stimulated towards an activated, inflammatory phenotype, supporting the potential of decellularized matrices for tissue engineering. This study also demonstrated that the differentiation surface affects MDM phenotype and therefore study design of macrophage interactions with biomaterials should scrutinize the specific macrophage culture method utilized and its effects on macrophage phenotype.

Relationships between geological phosphorite deposition and biological apatite nucleation have often been overlooked. However, similarities in biological apatite and phosphorite mineralogy suggest that their chemical formation mechanisms may be similar. This review serves to draw parallels between two newly described phosphorite mineralization processes, and proposes a similar novel mechanism for biologically controlled apatite mineral nucleation. This mechanism integrates polyphosphate biochemistry with crystal nucleation theory. Recently, the roles of polyphosphates in the nucleation of marine phosphorites were discovered. Marine bacteria and diatoms have been shown to store and concentrate inorganic phosphate (Pi) as amorphous, polyphosphate granules. Subsequent release of these P reserves into the local marine environment as Pi results in biologically induced phosphorite nucleation. Pi storage and release through an intracellular polyphosphate intermediate may also occur in mineralizing oral bacteria. Polyphosphates may be associated with biologically controlled apatite nucleation within vertebrates and invertebrates. Historically, biological apatite nucleation has been attributed to either a biochemical increase in local Pi concentration or matrix-mediated apatite nucleation control. This review proposes a mechanism that integrates both theories. Intracellular and extracellular amorphous granules, rich in both calcium and phosphorus, have been observed in apatite-biomineralizing vertebrates, protists, and atremate brachiopods. These granules may represent stores of calcium-polyphosphate. Not unlike phosphorite nucleation by bacteria and diatoms, polyphosphate depolymerization to Pi would be controlled by phosphatase activity. Enzymatic polyphosphate depolymerization would increase apatite saturation to the level required for mineral nucleation, while matrix proteins would simultaneously control the progression of new biological apatite formation.

Decellularized tissue-derived heart valves are an example of biomaterials derived from natural scaffolds. These types of implants are increasing in popularity although their in vivo performance is still only poorly understood and has, at times, been catastrophic. It is apparent that better understanding is required before these biomaterials can be used safely. In this study, the human monocyte-derived macrophage (MDM) response to decellularized bovine pericardium (DBP) was used as a model to predict the biological performance of these materials on implantation. Human monocytes differentiated on tissue culture polystyrene (TCPS) for 14 days were trypsinized and reseeded onto DBP, TCPS, and polydimethylsiloxane (PDMS) for 48 h. The MDMs on DBP contained less intracellular and extracellular esterase activity compared with MDMs on TCPS and PDMS, as well as less acid phosphatase activity than on TCPS. As well, morphologically, MDMs on DBP were less spread, less multinucleated and did not display many lamellipodia. Taken together, these data represent the first evidence of the MDM response to intact, native extracellular matrix, demonstrating that these cells reacted with an altered, possibly reduced foreign body response on this natural scaffold compared with the two control surfaces. This in vitro MDM cell model may provide a novel method for predicting and elucidating the biological performance of tissue-derived biomaterials, thereby directing a more rational design of biomaterials for tissue regeneration purposes.