A Review of the Foreign-body Response to Subcutaneously-implanted Devices: The Role of Macrophages and Cytokines in Biofouling and Fibrosis

Abstract

The biological response to implanted biomaterials in mammals is a complex series of events that involves many biochemical pathways. Shortly after implantation, fibrinogen and other proteins bind to the device surface, a process known as biofouling. Macrophages then bind to receptors on the proteins, join into multinucleated giant cells, and release transforming growth factor beta and other inflammatory cytokines. In response to these signals, quiescent fibroblasts are transformed into myofibroblasts, which synthesize procollagen via activation of Smad mediators. The procollagen becomes crosslinked after secretion into the extracellular space. Mature crosslinked collagen and other extracellular matrix proteins gradually contribute to formation of a hypocellular dense fibrous capsule that becomes impermeable or hypopermeable to many compounds. Porous substrates and angiogenic growth factors can stimulate formation of microvessels, which to some extent can maintain analyte delivery to implanted sensors. However, stimulation by vascular endothelial growth factor alone may lead to formation of leaky, thin-walled, immature vessels. Other growth factors are most probably needed to act upon these immature structures to create more robust vessels.During implantation of foreign bodies, the foreign-body response is difficult to overcome, and thousands of biomaterials have been tested. Biomimicry (i.e., creating membranes whose chemical structure mimics natural cellular compounds) may diminish the response, but as of this writing, it has not been possible to create a stealth material that circumvents the ability of the mammalian surveillance systems to distinguish foreign from self.

From Wearable Sensors to Smart Implants-–Toward Pervasive and Personalized Healthcare

“…The challenge of chronic sensing implants remains to be in the areas of long-term sensor stability, power management of active implants, and biocompatibility of embodiment. To this end, active sensor management schemes can be used to mitigate sensor degradation due to biofouling [59]. For active implants requiring an energy source, wireless power transmission ultrasultra [60] or ultrasonic [61] links doubling as a data-communication path can be deployed as a wireless battery charger for critical/non-interruptible implants such as a pacemaker.…”

Nonadjunctive Use of Continuous Glucose Monitoring for Diabetes Treatment Decisions

“…Sensor drift relates to the foreign body response bringing inflammatory cells to the sensor insertion cite, resulting in drift of the sensor signal possibly from these cells consuming oxygen and glucose as well as producing compounds such as hydrogen peroxide. 12 Sensor delay is related to the physiologic lag between interstitial glucose and blood glucose concentrations, 13,14 and is impacted by whether glucose levels are rising or falling. 15 Delay can also be imparted due to smoothing of the signal during processing.…”

Гигантские Клетки Инородных Тел И Тканевые Реакции На Поверхности Имплантатов

“…Прогрессирование фиброзных изменений с возможной последующей фрагментацией биоматериалов является пробле-мой при использовании маммарных протезов [1,2]. Отграничение малососудистой фиброзной тканью также нежелательно при имплантации биосенсоров глюкозы [56]. В сосудистой хирур-гии одним из негативных результатов использо-вания сосудистых протезов и стентов является появление тканевых условий для образования неоинтимы с возможным последующим рестено-зом.…”

“…Характер реакций соединительной ткани за-висит от структуры поверхности имплантатов, ее пористости [56]. Губчатые материалы (гидрокси-этилметакрилат, поливиниловые губки) вызывают формирование фиброзной капсулы и гигантокле-точной реакции.…”

“…W.K. Ward et al [55,56] установили, что подкожная имплантация пори-стых материалов с разным размером пор (поли-виниловые губки, E-PTFE) ведет к активному ан-гиогенезу в сравнении с солидными гладкими мембранами. Из большого количества исследова-ний влияния геометрии структуры биоматериалов на тканевую реакцию можно сделать два основ-ных вывода: 1) большинство клеток лучше связы-ваются с пористыми поверхностями, чем с глад-кими; 2) количество новообразованных капилля-ров больше на поверхности преимущественно пористых и тканных материалов в сравнении с гладкими.…”