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