Regenerative Engineering for Knee Osteoarthritis Treatment： Biomaterials and Cell-Based Technologies

Knee osteoarthritis （OA） is the most common form of arthritis worldwide. The incidence of this disease is rising and its treatment poses an economic burden. Two early targets of knee OA treatment include the predominant symptom of pain, and cartilage damage in the knee joint. Current treatments have been beneficial in treating the disease but none is as effective as total knee arthroplasty （TKA）. However, while TKA is an end-stage solution of the disease, it is an invasive and expensive procedure, Therefore, innovative regenerative engineering strategies should be established as these could defer or annul the need for a TKA. Several biomaterial and cell-based therapies are currently in development and have shown early promise in both preclinical and clinical studies. The use of advanced biomaterials and stem cells independently or in conjunction to treat knee OA could potentially reduce pain and regenerate fo- cal articular cartilage damage. In this review, we discuss the pathogenesis of pain and cartilage damage in knee OA and explore novel treatment options currently being studied, along with some of their limitations.

Scalable Electrophysiology of Millimeter-Scale Animals with Electrode Devices

Millimeter-scale animals such as Caenorhabditis elegans,Drosophila larvae,zebrafish,and bees serve as powerful model organisms in the fields of neurobiology and neuroethology.Various methods exist for recording large-scale electrophysiological signals from these animals.Existing approaches often lack,however,real-time,uninterrupted investigations due to their rigid constructs,geometric constraints,and mechanical mismatch in integration with soft organisms.The recent research establishes the foundations for 3-dimensional flexible bioelectronic interfaces that incorporate microfabricated components and nanoelectronic function with adjustable mechanical properties and multidimensional variability,offering unique capabilities for chronic,stable interrogation and stimulation of millimeter-scale animals and miniature tissue constructs.This review summarizes the most advanced technologies for electrophysiological studies,based on methods of 3-dimensional flexible bioelectronics.A concluding section addresses the challenges of these devices in achieving freestanding,robust,and multifunctional biointerfaces.

Engineering LNPs with polysarcosine lipids for mRNA delivery

Since the approval of the lipid nanoparticles(LNP)-mRNA vaccines against the SARS-CoV-2 virus,there has been an increased interest in the delivery of mRNA through LNPs.However,current LNP formulations contain PEG lipids,which can stimulate the generation of anti-PEG antibodies.The presence of these antibodies can potentially cause adverse reactions and reduce therapeutic efficacy after administration.Given the widespread deployment of the COVID-19 vaccines,the increased exposure to PEG may necessitate the evaluation of alternative LNP formulations without PEG components.In this study,we investigated a series of polysarcosine(pSar)lipids as alternatives to the PEG lipids to determine whether pSar lipids could still provide the functionality of the PEG lipids in the ALC-0315 and SM-102 LNP systems.We found that complete replacement of the PEG lipid with a pSar lipid can increase or maintain mRNA delivery efficiency and exhibit similar safety profiles in vivo.

LPA_(1) antagonist-derived LNPs deliver A20 mRNA and promote anti-fibrotic activities

Activated fibroblasts are major mediators of pulmonary fibrosis.Fibroblasts are generally found in the connective tissue but upon activation can generate excess extracellular matrix(ECM)in the lung interstitial section.Therefore,fibroblasts are one of the most targeted cells for treating idiopathic pulmonary fibrosis(IPF).Here,we develop an anti-fibrotic platform that can modulate both the lysophosphatidic acid receptor 1(LPA_(1))and the inflammatory pathway through tumor necrosis factorα-induced protein 3(TNFAIP3,also known as A20)in fibroblasts.First,we synthesized a series of LPA_(1) antagonists,AM095 and AM966,derived amino lipids(LA lipids)which were formulated into LA-lipid nanoparticles(LA-LNPs)encapsulating mRNA.Specifically,LA5-LNPs,with AM966 head group and biodegradable acetal lipid tails,showed efficient A20 mRNA delivery to lung fibroblasts in vitro(80.2%±1.5%)and ex vivo(17.2%±0.4%).When treated to primary mouse lung fibroblasts(MLF),this formulation inhibited fibroblast migration and collagen production,thereby slowing the progression of IPF.Overall,LA5-LNPs encapsulated with A20 mRNA is a novel platform offering a potential approach to regulate fibroblast activation for the treatment of IPF.

Emission of particulate and gaseous pollutants from household laser processing machine

Indoor air quality(IAQ) directly affects the health of occupants. Household manufacturing equipment(HME) used for hobbies or educational purposes is a new and unexplored source of air pollution. In this study, we evaluated the characteristics of particulate and gaseous pollutants produced by a household laser processing equipment(HLPE). Various target materials were tested using a commercial HLPE under various operating conditions of laser power and sheath air flow rate. The mode diameters of the emitted particles gradually decreased as laser power increased, while the particle number concentration(PNC) and particle emission rate(PER) increased. In addition, as the sheath air flow rate quadrupled from 10 to 40 L/min, the mode diameter of the emitted particles decreased by nearly 25%, but the effect on the PNC was insignificant. When the laser induced the target materials at 53 m W, the mode diameters of particles were < 150 nm, and PNCs were > 2.0 × 10^(4) particles/cm^(3). Particularly, analyses of sampled aerosols indicated that harmful substances such as sulfur and barium were present in particles emitted from leather. The carcinogenic gaseous pollutants such as acrylonitrile, acetaldehyde, 1,3-butadiene, benzene, and C 8 aromatics(ethylbenzene) were emitted from all target materials. In an actual indoor environment, the PNC of inhalable ultrafine particles(UFPs) was > 5 × 10^(4) particles/cm^(3) during 30 min of HLPE operation. Our results suggest that more meticulous control methods are needed, including the use of less harmful target materials along with filters or adsorbents that prevent emission of pollutants.