The host response to implanted biomaterials is a highly regulated process that influences device functionality and clinical outcome. Non-degradable biomaterials, such as knitted polypropylene mesh, frequently elicit a chronic foreign body reaction with resultant fibrosis. Previous studies have shown that an extracellular matrix (ECM) hydrogel coating of polypropylene mesh reduces the intensity of the foreign body reaction, though the mode of action is unknown. Macrophage participation plays a key role in the development of the foreign body reaction to biomaterials, and therefore the present study investigated macrophage polarization following mesh implantation. Spatiotemporal analysis of macrophage polarization was conducted in response to uncoated polypropylene mesh and mesh coated with hydrated and dry forms of ECM hydrogels derived from either dermis or urinary bladder. Pro-inflammatory M1 macrophages (CD86+/CD68+), alternatively activated M2 macrophages (CD206+/CD68+), and foreign body giant cells were quantified between 3-35 days. Uncoated polypropylene mesh elicited a dominant M1 response at the mesh fiber surface, which was decreased by each ECM coating type beginning at 7 days. The diminished M1 response was accompanied by a reduction in the number of foreign body giant cells at 14 and 35 days, though there was a minimal effect upon the number of M2 macrophages at any time. These results show that ECM coatings attenuate the M1 macrophage response and increase the M2/M1 ratio to polypropylene mesh in vivo.

Although calcium phosphate cement (CPC) is promising for bone repair, its clinical use requires on site powder-liquid mixing. To shorten surgical time and improve graft properties, it is desirable to develop premixed CPC in which the paste remains stable during storage and hardens only after placement into the defect. The objective of this study was to develop premixed CPC with rapid setting when immersed in a physiological solution. Premixed CPCs were formulated using the following approach: Premixed CPC = CPC powder + nonaqueous liquid + gelling agent + hardening accelerator. Three premixed CPCs were developed: CPC-monocalcium phosphate monohydrate (MCPM), CPC-chitosan, and CPC-tartaric. Setting time for these new premixed CPCs ranged from 5.3 to 7.9 min, significantly faster than 61.7 min for a premixed control CPC reported previously (p < 0.05). SEM revealed the formation of nano-sized needle-like hydroxyapatite crystals after 1 d immersion and crystal growth after 7 d. Diametral tensile strength for premixed CPCs at 7 d ranged from 2.8 to 6.4 MPa, comparable to reported strengths for cancellous bone and sintered porous hydroxyapatite implants. Osteoblast cells attained a normal polygonal morphology on CPC-MCPM and CPC-chitosan with cytoplasmic extensions adhering to the nano-hydroxyapatite crystals. In summary, fast-setting premixed CPCs were developed to avoid the powder-liquid mixing in surgery. The pastes hardened rapidly once immersed in physiological solution and formed hydroxyapatite. The cements had strengths matching those of cancellous bone and sintered porous hydroxyapatite and non-cytotoxicity similar to conventional non-premixed CPC.

Surgical mesh devices composed of synthetic materials are commonly used for ventral hernia repair. These materials provide robust mechanical strength and are quickly incorporated into host tissue; factors which contribute to reduced hernia recurrence rates. However, such mesh devices cause a foreign body response with the associated complications of fibrosis and patient discomfort. In contrast, surgical mesh devices composed of naturally occurring extracellular matrix (ECM) are associated with constructive tissue remodeling, but lack the mechanical strength of synthetic materials. A method for applying a porcine dermal ECM hydrogel coating to a polypropylene mesh is described herein with the associated effects upon the host tissue response and biaxial mechanical behavior. Uncoated and ECM coated heavy-weight BARD™ Mesh were compared to the light-weight ULTRAPRO™ and BARD™ Soft Mesh devices in a rat partial thickness abdominal defect overlay model. The ECM coated mesh attenuated the pro-inflammatory response compared to all other devices, with a reduced cell accumulation and fewer foreign body giant cells. The ECM coating degraded by 35 days, and was replaced with loose connective tissue compared to the dense collagenous tissue associated with the uncoated polypropylene mesh device. Biaxial mechanical characterization showed that all of the mesh devices were of similar isotropic stiffness. Upon explantation, the light-weight mesh devices were more compliant than the coated or uncoated heavy-weight devices. The present study shows that an ECM coating alters the default host response to a polypropylene mesh, but not the mechanical properties in an acute in vivo abdominal repair model.