Rational design of poly(peptide-ester) block copolymers for enzyme-specific surface resorption.

Tissue resorption and remodeling are pivotal steps in successful healing and regeneration, and it is important to design biomaterials that are responsive to regenerative processes in native tissue. The cell types responsible for remodeling, such as macrophages in the soft tissue wound environment and osteoclasts in the bone environment, utilize a class of enzymes called proteases to degrade the organic matrix. Many hydrophobic thermoplastics used in tissue regeneration are designed to degrade and resorb passively through hydrolytic mechanisms, leaving the potential of proteolytic-guided degradation underutilized. Here, we report the design and synthesis of a tyrosol-derived peptide-polyester block copolymer where protease-mediated resorption is tuned through changing the chemistry of the base polymer backbone and protease specificity is imparted through incorporation of specific peptide sequences. Quartz crystal microbalance was used to quantify polymer surface resorption upon exposure to various enzymes. Aqueous solubility of the diacids and the thermal properties of the resulting polymer had a significant effect on enzyme-mediated polymer resorption. While peptide incorporation at 2 mol% had little effect on the final thermal and physical properties of the block copolymers, its incorporation improved polymer resorption significantly in a peptide sequence- and protease-specific manner. To our knowledge, this is the first example of a peptide-incorporated linear thermoplastic with protease-specific sensitivity reported in the literature. The product is a modular system for engineering specificity in how polyesters can resorb under physiological conditions, thus providing a potential framework for improving vascularization and integration of biomaterials used in tissue engineering.

Polymer Texture Influences Cell Responses in Osteogenic Microparticles.

Introduction: Polymer materials used in medical devices and treatments invariably encounter cellular networks. For the device to succeed in tissue engineering applications, the polymer must promote cellular interactions through adhesion and proliferation. To predict how a polymer will behave in vitro, these material-cell interactions need to be well understood. Methods: To study polymer structure-property relationships, microparticles of four chemically distinct tyrosol-derived poly(ester-arylate) polymers and a commercially available poly(lactic acid-co-glycolic acid) (PLGA) copolymer were prepared and their interactions with cells investigated. Cell loading concentration was optimized and cell adhesion and proliferation evaluated. Particles were also tested for their ability to adsorb bone morphogenetic protein-2 (BMP-2) and differentiate a myoblast cell line towards an osteoblast lineage through BMP-2 loading and release. Results: While cell adhesion was observed on all particles after 24 h of incubation, the highest degree of cell adhesion occurred on polymers with smaller crystallites. At longer incubation times, cells proliferated on all particle formulations, regardless of the differences in polymer properties. High BMP-2 loading was achieved for all particle formulations and all formulations showed a burst release. Even with the burst release, cells cultured on all formulations showed an upregulation in alkaline phosphatase (ALP) activity, a measure of osteoblast differentiation. Conclusions: As with cell adhesion, the polymer with the smaller crystallite showed the most ALP activity. We suggest that smaller crystallites serve as a proxy for topographical roughness to elicit the observed responses from cells. Furthermore, we have drawn a correlation between the polymer crystallite with the hydration potential using surface analysis techniques. Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-022-00729-9.

Tyrosol Derived Poly(ester-arylate)s for Sustained Drug Delivery from Microparticles.

New biodegradable polymers are needed for use in drug delivery systems to overcome the high burst release, lack of sustained drug release, and acidic degradation products frequently observed in current formulations. Commercially available poly(lactide-co-glycolide) (PLGA) is often used for particle drug release formulations; however, it is often limited by its large burst release and acidic degradation products. Therefore, a biocompatible and biodegradable tyrosol-derived poly(ester-arylate) library has been used to prepare a microparticle drug delivery system which shows sustained delivery of hydrophobic drugs. Studies were performed using polymers with varying hydrophilicity and thermal properties and compared to PLGA. Various drug solubilizing cosolvents were used to load model drugs curcumin, dexamethasone, nicotinamide, and acyclovir. Hydrophobic drugs curcumin and dexamethasone were successfully loaded up to 50 weight percent (wt %), and a linear correlation between drug wt % loaded and the particle glass transition temperature (Tg) was observed. Both curcumin and dexamethasone were visible on the particle surface at 20 wt % loading and higher. By adjusting the polymer concentration during particle formation, release rates were able to be controlled. Release studies of dexamethasone loaded particles with a lower polymer concentration showed a biphasic release profile and complete release after 47 days. Particles prepared using a higher polymer concentration showed sustained release for up to 77 days. Comparably, PLGA showed a traditional triphasic release profile and complete release after 63 days. This novel tyrosol-derived poly(ester-arylate) library can be used to develop injectable, long-term release formulations capable of providing sustained drug delivery.

Optical Biosensors for Virus Detection: Prospects for SARS-CoV-2/COVID-19.

The recent pandemic of the novel coronavirus disease 2019 (COVID-19) has caused huge worldwide disruption due to the lack of available testing locations and equipment. The use of optical techniques for viral detection has flourished in the past 15 years, providing more reliable, inexpensive, and accurate detection methods. In the current minireview, optical phenomena including fluorescence, surface plasmons, surface-enhanced Raman scattering (SERS), and colorimetry are discussed in the context of detecting virus pathogens. The sensitivity of a viral detection method can be dramatically improved by using materials that exhibit surface plasmons or SERS, but often this requires advanced instrumentation for detection. Although fluorescence and colorimetry lack high sensitivity, they show promise as point-of-care diagnostics because of their relatively less complicated instrumentation, ease of use, lower costs, and the fact that they do not require nucleic acid amplification. The advantages and disadvantages of each optical detection method are presented, and prospects for applying optical biosensors in COVID-19 detection are discussed.

Opportunities for biomaterials to address the challenges of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has revealed major shortcomings in our ability to mitigate transmission of infectious viral disease and provide treatment to patients, resulting in a public health crisis. Within months of the first reported case in China, the virus has spread worldwide at an unprecedented rate. COVID-19 illustrates that the biomaterials community was engaged in significant research efforts against bacteria and fungi with relatively little effort devoted to viruses. Accordingly, biomaterials scientists and engineers will have to participate in multidisciplinary antiviral research over the coming years. Although tissue engineering and regenerative medicine have historically dominated the field of biomaterials, current research holds promise for providing transformative solutions to viral outbreaks. To facilitate collaboration, it is imperative to establish a mutual language and adequate understanding between clinicians, industry partners, and research scientists. In this article, clinical perspectives are shared to clearly define emerging healthcare needs that can be met by biomaterials solutions. Strategies and opportunities for novel biomaterials intervention spanning diagnostics, treatment strategies, vaccines, and virus-deactivating surface coatings are discussed. Ultimately this review serves as a call for the biomaterials community to become a leading contributor to the prevention and management of the current and future viral outbreaks.

Effect of mandibular titanium reconstructive plates on radiation dose.

BACKGROUND: The effects of the mandibular titanium alloy plates on the radiation-tissue interactions are not clearly defined. Photon beam radiation may be modified after striking a metal plate used to reconstruct the mandible after oncologic surgery. The purpose of this study was to determine, in a human mandible model, the effects of a titanium alloy plate on the radiation dose received at the bone/titanium (plate and screws) interface and bone/soft tissue interface. METHODS: We used an adult male human head and neck ex vivo model. A medical grade titanium alloy 6-hole plate, 2.4 mm, was fixed in the midline of the mandible. The mandible was then irradiated using 6 MV photon beams. Thermoluminescent dosimeters were used to measure the radiation doses anterior and posterior to the mandible. The experiment was then repeated without the plate and screws. RESULTS: The difference between the average doses received by the mandible reconstructed with plate/screws and a mandible without plate/screws was +2.1% at the buccal aspect of the mandible and +3.0% at the lingual aspect; respective P values were.741 and .323. Thus, these differences were not statistically significant. CONCLUSION: In this study, we did not observe any significant influence of titanium alloy plate/screws on the radiation doses received by tissues anterior or posterior to the mandible.