When regenerative medicine imitates nature

Bio­mim­icry is becom­ing increas­ingly pop­u­lar in bio­med­ic­al research. It per­meates both fun­da­ment­al bio­lo­gic­al research and the devel­op­ment of med­ic­al tech­no­logy. Here are a few examples.

A new turn­ing point for res­tor­at­ive medi­cine, which is on the way to becom­ing regen­er­at­ive, i.e. truly cap­able of restor­ing bio­lo­gic­al tis­sues and their func­tions. The aim is to repro­duce liv­ing organ­isms and their pro­cesses, in oth­er words to devel­op a bio­mi­met­ic approach to medi­cine. This is com­bined with anoth­er approach, bioen­gin­eer­ing, at the inter­sec­tion between mater­i­als sci­ence and the bio­lo­gic­al sci­ences. Cath­er­ine Picart, head of the Bio­mi­met­ics and Regen­er­at­ive Medi­cine team in the Biosanté Unit at CEA Gren­oble, is using these tools to cre­ate bio­ma­ter­i­als to repair bone tis­sue, in col­lab­or­a­tion with max­il­lo­fa­cial sur­geons at Annecy hos­pit­al.  The aim is to provide the dam­aged bone with an envir­on­ment in which it can rebuild itself. To do this, the team designs bio­ma­ter­i­als con­tain­ing bone growth factors. They are 3D-prin­ted and a bio­mi­met­ic film, known as an “osteoin­ducer”, is applied to encour­age bone regeneration.

These bio­ma­ter­i­als are poly­mers that resemble the extra­cel­lu­lar mat­rix, the bio­lo­gic­al gel found between anim­al cells. This cross-linked poly­mer is com­posed of hya­lur­on­ic acid, a poly­mer found in the skin and cap­able of form­ing very thin films on which growth factor, the pro­tein that con­trols bone growth, can be depos­ited. The film is depos­ited on the sur­face of a por­ous bio­ma­ter­i­al pro­duced by 3D print­ing. The cells adhere to it and fill the spaces, pro­du­cing bone. This was demon­strated in rodent mod­els in 2016¹.

This approach has also proved its worth in large anim­als (pigs, sheep) with bone defects in the jaw and leg²³. In humans, this type of mal­form­a­tion cur­rently requires sev­er­al bone graft­ing oper­a­tions. With the concept of bone regen­er­a­tion, it could be as simple as graft­ing syn­thet­ic bone and leav­ing it to rebuild itself.

This tech­nique has the advant­age of pro­du­cing a cus­tom­ised, made-to-meas­ure res­tor­a­tion. The 3D mould con­trols the shape and poros­ity of the restored bone, while the sur­face film defines its quant­ity and the speed at which it grows back.

In addi­tion to this bio­mi­met­ic approach, anoth­er focus of the team is to under­stand how these arti­fi­cial matrices, com­bined with growth factors, act on cells. In par­tic­u­lar, the aim is to repro­duce in vitro the con­trol they exert over cell com­mu­nic­a­tion and tis­sue form­a­tion⁴. 

The dif­fi­culty with this work is that the rigid­ity of the sur­faces affects the response of the cells. The Gren­oble research­ers have there­fore developed an approach using flex­ible bio­mi­met­ic films that are less than two micro­metres thick. The films are depos­ited on 96-well plates, com­monly used in bio­med­ic­al research. Each well can there­fore con­sti­tute an exper­i­ment­al con­di­tion, and 96 exper­i­ments can be car­ried out sim­ul­tan­eously, each with dif­fer­ent mat­rix or growth factor compositions.

This approach provides insights into the molecu­lar mech­an­isms of bone tis­sue form­a­tion, which may be use­ful for the clin­ic­al approach to bone repair.

Bio­mim­icry also makes it pos­sible to cre­ate new med­ic­al tools, par­tic­u­larly for sur­gery. There is a whole range of med­ic­al tech­no­lo­gies that seek to repro­duce the prop­er­ties of cer­tain anim­al or plant spe­cies. One such example is sur­gic­al needles⁵ inspired by para­sit­ic wasps, developed by the uni­ver­sit­ies of Delft and Wagen­in­gen. Ultra-thin, these needles are made up of sev­en inde­pend­ent rods that ensure the elasti­city and strength of the system.

Also in the field of sur­gery, research­ers at the Amer­ic­an Uni­ver­sity of Illinois have cre­ated a suc­tion cup inspired by the octopus⁶ and designed to trans­fer del­ic­ate tis­sue dur­ing trans­plants. This sys­tem uses the elec­tro­therm­al prop­er­ties of a poly­mer to repro­duce the del­ic­ate suc­tion of the tentacles.

Sur­gic­al adhes­ives are anoth­er very prom­ising field of bio­mi­met­ic tools. French com­pany Tis­si­um⁷ appears to be one of the most advanced in this field. The Par­is-based com­pany has repro­duced the prop­er­ties of a mar­ine worm, Phrag­ma­to­poma cali­for­nica, which builds sand castles to house its colon­ies. A water-res­ist­ant cement ensures the solid­ity of the edi­fices. A prop­erty that is of great interest to the sur­gic­al community.

From fun­da­ment­al research to med­ic­al tech­no­logy, the concept of bio­mim­icry is driv­ing med­ic­al innov­a­tion. A study⁸ by the Indo-Brit­ish stra­tegic ana­lys­is firm Pre­ced­ence Research estim­ates that the bio­mi­met­ic med­ic­al innov­a­tion mar­ket will be worth more than 33 bil­lion dol­lars in 2022 and could reach 65 bil­lion dol­lars in 2032. These estim­ates are undoubtedly based on a broad defin­i­tion of bio­mi­met­ic innov­a­tion, but they point to a trend in which a great deal of research will be enter­ing the mar­ket in the next few years.

Agnès Vernet