Bioinspired Biohybrid Variable Stiffness Actuators For Bone Tissue Engineering

We have already covered a detailed article on actuators and the classification based on motion, energy source, and special actuators dealing with Piezoelectric effect and shape memory alloy. But there’s more to soft actuators dealing with shape versatility and variable stiffness components to achieve morphing robotics and in bionics. Variable stiffness properties had been a part of mammalian physiology way before the introduction of soft actuators in bone treatment. 

Taking a step back to understand the motive behind variable-stiffness actuators (VSAs), these mechatronic devices are designed to be deployed in various fields of science including medicine and tissue engineering. The devices are expanding their reach into humanoid robotic platforms that require VSAs with multiple degrees of freedom in robotic joints. Due to shaping versatility and effective interaction with biological parameters, the new research paper discusses a biohybrid (including biological and non-biological components) variable stiffness soft actuator that can self-create bone.

In the paper, “Biohybrid Variable-Stiffness Soft Actuators that Self-Create Bone,” the authors report the methodology to design a biohybrid variable stiffness actuator that integrates biological components enabling the development of variable stiffness systems and functionalities. 

Schematic illustration of the electrochemical behavior of PPy-Alg actuators with and without PMNFs [Image Credit: Research Paper]

Bioinspired biohybrid VSAs are designed using the electroactive polymer polypyrrole (PPy) as the mechanically active component which is combined with alginate hydrogels. These functionalize as cell-derived plasma membrane nanofragments as the bio-inducing source for mineralization (deposition of minerals on the bone matrix for the development of bone) and stiffening process of the gel layer. Through this methodology, the innovators develop unique soft-to-hard variable stiffness actuators that can be potentially used in the process of bone development. Previously reported demonstrations also showed the ability of plasma membrane nanofragments to promote the formation of bone through rapid mineralization in around 2 to 3 days while the conventional style of live cells or recombinant TNALP takes a minimum of 2 to 3 weeks.

“These variable-stiffness devices can wrap around and, after the PMNF-induce mineralization in and on the gel layer, adhere and integrate onto bone tissue,” the researcher explains in the abstract of the paper. “The developed biohybrid variable-stiffness actuators can be used in soft (micro-) robotics and as potential tools for bone repair or bone tissue engineering.”

One of the basic questions that come to our mind when designing such complex and critical devices is, does the biohybrid device maintain other parameters of bone development like membrane-bound enzymes and proteins? This is why plasma membrane nanofragments have become an important factor in novel functional biohybrid materials as they maintain a natural state allowing their optimal activity. The other combination along with polymer polypyrrole in the formation of bilayer actuator, alginate (Alg), is soft in nature and has been widely used in tissue engineering to allow functionalization with biomolecules.

Biocompatibility of the Biohybrid Actuators

After a series of experimentation of the plain bilayer actuator without the introduction of PMNF, followed by the formation of PPy-Alg-PMNF actuators to investigate the performance. Additionally, to improve the functionality of the bilayer actuator, the researchers embedded the Alg gel layer with a directional topographic pattern using photolithography. “This   designed   structure   controls   the   bending   shape   of   the bilayer actuator and enables the fabrication of actuators with embedded intelligence, that  is, morphological computing.”

Figures (a) and (b) show the movement photographs while (c) and (d) give out more information on the PPy-Alg-PMNF actuator after incubation in DMEM and 0.1m NaCl solution for 3, 5, and 7 days. [Image Credit: Research Paper]

To evaluate the potential deployment of the VSAs in tissue engineering, the PPy-Alg-PMNF actuators are wrapped around the bone to check the integration and interaction with the bone tissue. The actuator incubated in sodium chloride could separate from the bone, showing no fixation while the same PPy-Alg-PMNF actuator in DMEM initiated the adhesion to the bone. Manual wrapping of PPy-Alg-PMNF actuator with bone shows better adhesion. 

Even though all individual elements of the biohybrid actuators are highly biocompatible both in vitro and in vivo studies, future research could dwell on the analysis of chemical, physical and biological interactions with the living cells. Also, it is very important to optimize the strength of the newly formed bone to possess enough strength and load-bearing properties.  

Finally, looking back at the propositions made in the research paper:

1. A new concept of bio-induced variable-stiffness actuators with shape versatility to grow on the existing bone.

2. An embedded device with morphological computing enables the fixation of the device in a defined shape.

3. PMNF-based biohybrid actuators are the future for designing new tools in tissue engineering.

The research paper is published on Wiley Online Library under open access to community viewing. If you are interested in reading more details on the experimentation of the biohybrid variable-stiffness actuator, head to the official article page.

References

Cao, D., Martinez, J. G., Hara, E. S., Jager, E. W. H., Biohybrid Variable-Stiffness Soft Actuators that Self-Create Bone. Adv. Mater. 2022, 2107345. https://doi.org/10.1002/adma.202107345

S. Wolf et al., "Variable Stiffness Actuators: Review on Design and Components," in IEEE/ASME Transactions on Mechatronics, vol. 21, no. 5, pp. 2418-2430, Oct. 2016, doi: 10.1109/TMECH.2015.2501019.