Although people are endeavoring to develop synthetic piezoelectric materials, nature seems to have grasped the effect for millions of years.

In 1880, Curie brothers first discovered and demonstrated the piezoelectric effect, which is an intrinsic property of crystals with a non-centrosymmetric structure that allows robust and precise conversion between electrical and mechanical energies. Indeed, the piezoelectric effect has been observed in diverse biological systems. From the first discovery of piezoelectricity in wool and hair in 1941 to the Nobel Prize in Physiology or Medicine in 2021, which revealed that cells perceive pressure and trigger tactile sensation through the electromechanical coupling effect of proteins Piezo 1 and Piezo 2, piezoelectric biomaterials have always been mysterious and attractive to researchers. The generation of bioelectricity from the piezoelectric effect has physiological significance in living systems, such as the piezoelectric charges generated by the human tibia during walking, which affects bone remodeling and growth. Additionally, piezoelectric potential in the lung generated during respiration could assist in binding oxygen to hemoglobin.

Recently, piezoelectric biomaterials have garnered great interest in biomedical applications due to their biocompatibility, biodegradability, accessibility, and environmental sustainability. However, the piezoelectric response of biomaterials (bone:0.2 pm V^-1) is very weak compared to piezoceramics (PZT: 500 pm V^-1) and even polymers (PVDF: 30 pm V^-1) because of their random polarization and lack of ferroelectricity. Besides, the large-scale assembly and domain alignment of piezoelectric biomaterials remain challenging. Among the biomaterials, glycine, the simplest non-chiral amino acid, has three distinct crystallization polymorphs, non-piezoelectric α-glycine, piezoelectric β-glycine, and piezoelectric γ-glycine. β-glycine crystals exhibit high shear piezoelectricity (178 pm V^-1) and marvelous piezoelectric voltage coefficient (8 Vm N^-1) larger than any currently used ceramic or polymer. Unfortunately, β-glycine is the most difficult to form in kinetics and the most unstable in thermodynamics under ambient conditions. The excessively high coercive electric field also makes it quite challenging to polarize glycine crystals and align the domains at the macroscale, even though they are ferroelectric. 

In our work, we present an active self-assembly strategy to tailor piezoelectric biomaterial thin films via synergistic nanoconfinement and in-situ poling. The nanoconfinement-induced homogeneous nucleation overcomes the interfacial dependency and allows the electric field applied in-situ to align ferroelectric domains across the entire film during synthesis. The β-glycine films exhibit an enhanced piezoelectric strain coefficient of 11.2 pm V^-1 and an exceptional piezoelectric voltage coefficient of 252×10^-3 Vm N^-1, which is an order of magnitude larger than that of the state-of-the-art PZT. Of particular significance is that the nanoconfinement effect greatly improves the thermostability before melting (192 °C). 

The β-glycine nanocrystalline films are fabricated based on a bio-organic film printer using the electrohydrodynamic spray method (Fig. 1a). With the rapid water evaporation and the increasingly large surface-area-to-volume ratio of the nano-micro droplets, the glycine nucleus is formed in the β phase through the nanoconfinement effect (Figs. 1b, 1c, and 1d). The in-situ electric field in the crystal growth process induces the domain alignment of β-glycine nanocrystals, suggesting the net polarization direction [020] is parallel to the electric field (Fig. 1e). The as-synthesized film resembles the inorganic polycrystalline morphology and it can be constructed in variable sizes and customizable structures on various rigid or flexible substrates (Figs. 1f, 1g). 

The SEM images show the uniform and compact nanograin distribution of β-glycine films (Figs. 2a and 2b). XRD spectra confirm the pure β crystalline phase of the nanocrystalline films, where the strongest peak (020) manifests that the OOP orientation is dominated by being along the optimal piezoelectric direction (red curve in Fig. 2c). On the contrary, without either in-situ electric field or nanoconfinement, the β-glycine crystals show a dominant OOP orientation [001] that is perpendicular to the strongest piezoelectric direction (green curve and blue curve in Fig. 2c). They hardly exhibit piezoelectricity at a macroscopic level since the piezoelectric effects of the opposite domains will cancel out each other, which evidences the indispensable effect of the synergy of nanoconfinement and in-situ poling on domain alignment.

The piezoelectric properties of the as-prepared β-glycine nanocrystalline films are evaluated by piezoresponse force microscopy (PFM) measurements. Fig. 3a illustrates the PFM mapping of OOP amplitudes, exhibiting superb and uniform piezoelectric response of the compact nanocrystals. The PFM OOP phase mapping is uniform and exhibits hardly any opposite phase, indicating that the ferroelectric domains of the as-prepared films are well aligned, and the polarization direction of the nanograins is consistent (Fig. 3b). The linearly fitted effective piezoelectric coefficient is around 11.2 pm V^-1 (red curve in Fig. 3c). which is superior compared to most reported bio-organic films (Fig. 3d). The uniform and high-value d₃₃ could be attributed to the excellent alignment of ferroelectric domains due to in-situ poling during the β-glycine homogeneous nucleation, which exposes most of the (020) polar surface toward the OOP direction. 

Besides piezoelectricity, thermostability is also a key figure of merit of piezoelectric materials for applications over a broad temperature range. Unfortunately, bulk β-glycine crystals are the least stable and readily transform to α-glycine in moist air after being left at room temperature for several hours or heated to 67 °C. Hence, we investigate the thermostability and phase transition properties of the as-prepared β-glycine nanocrystalline films. Through the DSC and in situ XRD results, we confirm no phase other than the β phase is observed throughout the heating process, indicating the absence of a Curie transition prior to the melting temperature of 192 °C. The infinite thermostability of the films results from the nanoconfinement effect. This is supported by the Ostwald step rule, an otherwise metastable form of a crystalline substance, β-glycine, actually becomes the stable form when the crystal size is constrained to nanometer-scale dimensions. We then compare the piezoelectric voltage coefficient g₃₃ of several actively studied piezoelectric material systems together with the β-glycine nanocrystalline films as a function of curie temperature (T_C) (Fig. 4). The melting temperature of 192 °C of the β-glycine nanocrystalline films is higher than the T_C of most piezoelectric materials and comparable to that of PZT-5H type piezoceramics. Notably, the g₃₃ of the β-glycine nanocrystalline films is on the same order of magnitude as PVDF, but with much higher T_C. 

In summary, our work addresses the long-standing challenge of synthesizing large-scale high-performance piezoelectric biomaterials. The excellent output performance, natural biocompatibility, and biodegradability of the β-glycine nanocrystalline films are of practical implications for high-performance biological electromechanical microdevices and transient bioelectronics. The proposed strategy is scalable to create films with variable dimensions, programmable structures, and diverse material forms such as flexible composites. Furthermore, this finding offers a generally applicable strategy for designing large-scale films of various biomaterials and other piezoelectric materials such as molecular or organic-inorganic piezoelectric materials.