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