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Small-angle X-ray and neutron scattering (SAXS and SANS) patterns from certain semicrystalline polymers and liquid crystals contain discrete reflections from ordered assemblies and central diffuse scattering (CDS) from uncorrelated structures. Systems with imperfectly ordered lamellar structures aligned by stretching or by a magnetic field produce four distinct SAXS patterns: two-point 'banana', four-point pattern, four-point 'eyebrow' and four-point 'butterfly'. The peak intensities of the reflections lie not on a layer line, or the arc of a circle, but on an elliptical trajectory. Modeling shows that randomly placed lamellar stacks modified by chain slip and stack rotation or interlamellar shear can create these forms. On deformation, the isotropic CDS becomes an equatorial streak with an oval, diamond or two-bladed propeller shape, which can be analyzed by separation into isotropic and oriented components. The streak has elliptical intensity contours, a natural consequence of the imperfect alignment of the elongated scattering objects. Both equatorial streaks and two- and four-point reflections can be fitted in elliptical coordinates with relatively few parameters. Equatorial streaks can be analyzed to obtain the size and orientation of voids, fibrils or surfaces. Analyses of the lamellar reflection yield lamellar spacing, stack orientation (interlamellar shear) angle α and chain slip angle ϕ, as well as the size distribution of the lamellar stacks. Currently available computational tools allow these microstructural parameters to be rapidly refined.

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We present an efficient approach for synthesizing cationic poly(ethylene imine) derivatives using the multicomponent split-Ugi reaction to rapidly create a library of complex functional ionizable lipopolymers. We synthesized a diverse library of 155 polymers, formulated them into polyplexes to establish structure-activity relationships crucial for endosomal escape and efficient transfection. After discovering a lead structure, lipopolymer-lipid hybrid nanoparticles are introduced to preferentially deliver to and elicit effective mRNA transfection in lung endothelium and immune cells, including T cells with low in vivo toxicity. The lipopolymer-lipid hybrid nanoparticles showed 300-fold improvement in systemic mRNA delivery to the lung compared to in vivo -JetPEI ® . Lipopolymer-lipid hybrid nanoparticles demonstrated efficient delivery of mRNA-based therapeutics for treatment of two different disease models. Lewis Lung cancer progression was significantly delayed after treatment with loaded IL-12 mRNA in U155@lipids after repeated i.v. administration. Systemic delivery of human CFTR (hCFTR) mRNA resulted in production of functional form of CFTR protein in the lungs. The functionality of hCFTR protein was confirmed by restoration of CFTR- mediated chloride secretion in conductive airway epithelia in CFTR knockout mice after nasal instillation of hCFTR mRNA loaded U155@lipids. We further showed that, U155@lipids nanoparticles can deliver complex CRISPR-Cas9 based RNA cargo to the lung, achieving 5.6 ± 2.4 % gene editing in lung tissue. Moreover, we demonstrated successful PD-1 gene knockout of T cells in vivo . Our results highlight a versatile delivery platform for systemic delivering of mRNA of various sizes for gene therapy for a variety of therapeutics.

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OBJECTIVE: Dyadic coping, the process of coping that transpires between couples challenged by one partner's illness, is an important predictor of disease adjustment and patient well-being. However, the extent of dyadic coping in rheumatoid arthritis (RA) remains unclear. This study examines the effect of dyadic coping on psychological distress and relationship quality from the perspectives of both participants with RA and their spouses. METHODS: Participants and their spouses were invited to participate in an online survey study if they were aged ≥ 18 years and had lived together for more than a year. The survey included the Chronic Pain Grade Scale, Dyadic Coping Inventory, Depression Anxiety Stress Scale, and Dyadic Adjustment Scale. Participants and spouses completed the survey independently. The actor-partner interdependence model was used to analyze the dyadic data. RESULTS: One hundred sixty-three couples participated. Our findings showed that participants who reported higher supportive dyadic coping reported lower depression, anxiety, and stress, and higher relationship quality, whereas participants who reported higher negative dyadic coping reported higher depression, anxiety, and stress, and lower relationship quality. Spouses who reported higher supportive dyadic coping reported higher relationship quality, but no effect on depression, anxiety, and stress was observed. In contrast, spouses who reported higher negative dyadic coping reported higher levels of depression, anxiety, and stress, and lower relationship quality. CONCLUSION: Participants' and spouses' perceptions of supportive and negative dyadic coping closely influenced their psychological distress and relationship quality. Further, having a partner with RA also seemed to affect the spouse, especially when there was a negative dyadic coping pattern.

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OBJECTIVES: To examine the historical trends and predict the future rates and total volumes of permanent residential aged care (PRAC) service utilization in Australia. DESIGN: A population-based repeated cross-sectional and projection study of non-indigenous older people (≥65 years) accessing PRAC in Australia was conducted. SETTING AND PARTICIPANTS: Publicly available aged care admissions from the Australian Institute of Health and Welfare and population estimates from the Australian Bureau of Statistics were used. METHODS: Historical incidence rates (per 1000 people), incidence rate ratios (IRRs) and 95% CIs of PRAC admission from 2008-2009 to 2020-2021 were estimated using negative binomial regression models. The future incidence and prediction intervals (PIs) of PRAC admission between 2021-2022 and 2051-2052 were projected using a generalized additive model-negative binomial regression. All estimates were adjusted or standardized by sex and age. RESULTS: Between 2008-2009 and 2020-2021, the adjusted admission to PRAC decreased (from 23.6/1000 people to 15.7/1000 people with an IRR = 0.97/year, 95% CI 0.97-0.98). The projected PRAC admission rate will decrease to 12.1/1000 (95%PI 10.8-13.3) by 2037-2038 and 9.0/1000 (95%PI 7.6-10.4) by 2051-2052. The projected volume of PRAC admission will be 73,988 (95%PI 65,960-81,425) at its highest point in 2037-2038 and 64,579 (95%PI 54,258-74,543) in 2051-2052. CONCLUSIONS AND IMPLICATIONS: The utilization of PRAC has decreased in the past decade, and a predicted decrease in PRAC use in future years is estimated. However, the volume of PRAC utilization will still increase for the next 15 years (until 2037-2038) due to our increasingly older population. These findings can inform service planning of PRAC access in Australia.

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Drug release from polymeric nanoparticles (NPs) is governed by their adsorption onto cell membranes and transmigration across cell walls. These steps are influenced by their interactions with proteins near the cells. These interactions were investigated by studying the sequential adsorption of plasma proteins, albumin (Alb) and fibrinogen (Fg), and micellar NPs using quartz crystal microbalance with dissipation (QCMD), X-ray photoelectron spectroscopy (XPS), and small-angle X-ray scattering (SAXS). The three NPs in the study all have poly(ethylene glycol) (PEG) shells but different cores: amorphous poly(propylene oxide) (PPO), crystalline polycaprolactone (PCL), and poly(desaminotyrosyl-tyrosine octyl ester-co-suberic acid) (DTO-SA). None of the NPs adsorbed onto a pre-adsorbed Fg layer. On the other hand, when the deposition sequence was reversed, Fg was adsorbed onto DTO-SA NP and PCL NP surfaces, but not onto the PPO NP surface. The interactions with Alb were different: DTO-SA did not adsorb onto Alb and vice versa; PPO NP adsorbed onto an Alb layer, but Alb did not adsorb onto the PPO NP layer; and PCL NP reversibly adsorbed onto Alb, but Alb displaced pre-adsorbed PCL NP. Thus, in most instances, the adsorption behavior was asymmetric in that it was dependent on the order of arrival of the adsorbates at the substrate. SAXS data did not show evidence for complex formation in solution. Thus, the solution behavior appears not to be a predictor of the interaction of proteins and the NPs near surfaces. Differing strengths of pairwise interactions of proteins, NPs and substrates account for this adsorption behavior. These differences in interactions could be the results of deformation of the adsorbates immobilized at the surface and the different degrees of surface remodeling that occur upon adsorption. Deformation could lead to disassembly of the NPs that has implications on their ability to release their payload of drugs upon adsorption onto tissue surfaces.

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BACKGROUND: Narcolepsy type 1 is caused by severe loss or lack of brain orexin neuropeptides. METHODS: We conducted a phase 2, randomized, placebo-controlled trial of TAK-994, an oral orexin receptor 2-selective agonist, in patients with narcolepsy type 1. Patients with confirmed narcolepsy type 1 according to clinical criteria were randomly assigned to receive twice-daily oral TAK-994 (30 mg, 90 mg, or 180 mg) or placebo. The primary end point was the mean change from baseline to week 8 in average sleep latency (the time it takes to fall asleep) on the Maintenance of Wakefulness Test (range, 0 to 40 minutes; normal ability to stay awake, ≥20 minutes). Secondary end points included the change in the Epworth Sleepiness Scale (ESS) score (range, 0 to 24, with higher scores indicating greater daytime sleepiness; normal, <10) and the weekly cataplexy rate. RESULTS: Of the 73 patients, 17 received TAK-994 at a dose of 30 mg twice daily, 20 received 90 mg twice daily, 19 received 180 mg twice daily, and 17 received placebo. The phase 2 trial and an extension trial were terminated early owing to hepatic adverse events. Primary end-point data were available for 41 patients (56%); the main reason for missing data was early trial termination. Least-squares mean changes to week 8 in average sleep latency on the MWT were 23.9 minutes in the 30-mg group, 27.4 minutes in the 90-mg group, 32.6 minutes in the 180-mg group, and -2.5 minutes in the placebo group (difference vs. placebo, 26.4 minutes in the 30-mg group, 29.9 minutes in the 90-mg group, and 35.0 minutes the 180-mg group; P<0.001 for all comparisons). Least-squares mean changes to week 8 in the ESS score were -12.2 in the 30-mg group, -13.5 in the 90-mg group, -15.1 in the 180-mg group, and -2.1 in the placebo group (difference vs. placebo, -10.1 in the 30-mg group, -11.4 in the 90-mg group, and -13.0 in the 180-mg group). Weekly incidences of cataplexy at week 8 were 0.27 in the 30-mg group, 1.14 in the 90-mg group, 0.88 in the 180-mg group, and 5.83 in the placebo group (rate ratio vs. placebo, 0.05 in the 30-mg group, 0.20 in the 90-mg group, and 0.15 in the 180-mg group). A total of 44 of 56 patients (79%) receiving TAK-994 had adverse events, most commonly urinary urgency or frequency. Clinically important elevations in liver-enzyme levels occurred in 5 patients, and drug-induced liver injury meeting Hy's law criteria occurred in 3 patients. CONCLUSIONS: In a phase 2 trial involving patients with narcolepsy type 1, an orexin receptor 2 agonist resulted in greater improvements on measures of sleepiness and cataplexy than placebo over a period of 8 weeks but was associated with hepatotoxic effects. (Funded by Takeda Development Center Americas; TAK-994-1501 and TAK-994-1504 ClinicalTrials.gov numbers, NCT04096560 and NCT04820842.).

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Objective: Screen time guidelines recommend no screens under two years due to the potential negative impacts on development. While current reports suggest many children exceed this, research relies on parent reports of their children's screen exposure. We objectively assess screen exposure during the first two years and how it differs by maternal education and gender. Methods: This Australian prospective cohort study used speech recognition technology to understand young children's screen exposure over an average day. Data collection occurred every six months when children were 6, 12, 18 and, 24 months old (n = 207). The technology provided automated counts of children's exposure to electronic noise. Audio segments were then coded as screen exposure. Prevalence of screen exposure was quantified, and differences between demographics examined. Results: At six months, children were exposed to an average of 1hr, 16 min (SD = 1hr, 36 min) of screens per day, increasing to an average of 2 h, 28 min (SD = 2 h, 4 min) by 24-months. Some children at six months were exposed to more than 3 h of screen time per day. Inequalities in exposure were evident as early as six months. Children from higher educated families were exposed to 1hr,43 min fewer screens per day, 95%CI (-2hr, 13 min, -1hr, 11 min) compared to lower educated households, with this difference remaining consistent as children age. Girls were exposed to an additional 12 min of screens 95%CI (-20 min, 44 min) per day compared to boys at six months, but this difference reduced to only 5 min by 24-months. Conclusion: Using an objective measure of screen exposure, many families exceed screen time guidelines, the extent increasing with child's age. Furthermore, substantial differences between maternal education groups emerge as young as six months old. This highlights the need for education and supports for parents around screen use in the early years, balanced within the realities of modern life.

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Objective. With the ultimate goal of reconstructing 3D elasticity maps from ultrasound particle velocity measurements in a plane, we present in this paper a methodology of inverting for 2D elasticity maps from measurements on a single line.Approach. The inversion approach is based on gradient optimization where the elasticity map is iteratively modified until a good match is obtained between simulated and measured responses. Full-wave simulation is used as the underlying forward model to accurately capture the physics of shear wave propagation and scattering in heterogeneous soft tissue. A key aspect of the proposed inversion approach is a cost functional based on correlation between measured and simulated responses.Main results. We illustrate that the correlation-based functional has better convexity and convergence properties compared to the traditional least-squares functional, and is less sensitive to initial guess, robust against noisy measurements and other errors that are common in ultrasound elastography. Inversion with synthetic data illustrates the effectiveness of the method to characterize homogeneous inclusions as well as elasticity map of the entire region of interest.Significance. The proposed ideas lead to a new framework for shear wave elastography that shows promise in obtaining accurate maps of shear modulus using shear wave elastography data obtained from standard clinical scanners.

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Objective. Arterial viscosity is emerging as an important biomarker, in addition to the widely used arterial elasticity. This paper presents an approach to estimate arterial viscoelasticity using shear wave elastography (SWE).Approach. While dispersion characteristics are often used to estimate elasticity from SWE data, they are not sufficiently sensitive to viscosity. Driven by this, we develop a full waveform inversion (FWI) methodology, based on directly matching predicted and measured wall velocity in space and time, to simultaneously estimate both elasticity and viscosity. Specifically, we propose to minimize an objective function capturing the correlation between measured and predicted responses of the anterior wall of the artery.Results. The objective function is shown to be well-behaving (generally convex), leading us to effectively use gradient optimization to invert for both elasticity and viscosity. The resulting methodology is verified with synthetic data polluted with noise, leading to the conclusion that the proposed FWI is effective in estimating arterial viscoelasticity.Significance. Accurate estimation of arterial viscoelasticity, not just elasticity, provides a more precise characterization of arterial mechanical properties, potentially leading to a better indicator of arterial health.

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AIM: To describe the cumulative incidence of child protection (CP) system contact, maltreatment type, source of reports to age 7 years, and socio-demographic characteristics for culturally and linguistically diverse (CALD) Australian children. METHODS: We used CP, education, health, and birth registrations data for children followed from birth up to age 7 from the South Australian Better Evidence, Better Outcomes, Linked Data (SA BEBOLD) platform. PARTICIPANTS: SA born children enrolled in their first year of school from 2009 to 2015 (n = 76 563). CALD defined as non-Aboriginal or Torres Strait Islander, spoken language other than English, Indigenous or Sign, or had at least one parent born in a non-English speaking country. OUTCOMES MEASURES: For CALD and non-CALD children, we estimated the cumulative incidence (risk) of CP contacts up to age 7, relative risk and risk differences for all levels of CP contact from notification to out-of-home care (OOHC), primary maltreatment type, reporter type, and socio-economic characteristics. Sensitivity analyses explored different population selection criteria and CALD definitions. RESULTS: By age 7, 11.2% of CALD children had 'screened-in' notifications compared to 18.8% of non-CALD (risk difference [RD] 7.6 percentage points (95% confidence interval: 6.9-8.3)), and 0.6% of CALD children experienced OOHC compared to 2.2% of non-CALD (RD 1.6 percentage points (95% confidence interval: 1.3-1.8)). Emotional abuse was the most common substantiated maltreatment type for CALD and neglect for non-CALD. Among both groups, the most common reporter sources were police and education sector. Socio-economic characteristics were broadly similar. Sensitivity analyses results were consistent with primary analyses. CONCLUSION: By age 7, CALD children had lower risk of contact with all levels of CP. Estimates based on primary and sensitivity analyses suggested CALD children were 5-9 percentage points less likely to have a report screened-in, and from 1.0 to 1.7 percentage points less likely to have experienced OOHC.

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The risk ratio (RR) is the ratio of the outcome among the exposed to risk of the outcome among the unexposed. This is a simple concept, which makes one wonder why it has not gained the same popularity as the odds ratio. Using logistic regression to estimate the odds ratio is quite common in epidemiology and interpreting the odds ratio as a risk ratio, under the assumption that the outcome is rare, is also common. On one hand, estimating the odds ratio is simple but interpreting it is hard. On the other, estimating the risk ratio is challenging but its interpretation is straightforward. Issues with estimating risk ratio still remain after four decades. These issues include convergence of the algorithm, the choice of regression specification (e.g. log-binomial, Poisson) and many more. Various new computational methods are available which help overcome the issue of convergence and provide doubly robust estimates of RR.

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OBJECTIVES: This study developed predictive models for one-week acute and six-month persistent pain following root canal treatment (RCT). An additional aim was to study the gain in predictive efficacy of models containing clinical factors only, over models containing sociodemographic characteristics. METHODS: A secondary data analysis of 708 patients who received RCTs was conducted. Three sets of predictors were used: (1) combined set, containing all predictors in the data set; (2) clinical set and (3) sociodemographic set. Missing data were handled by multiple imputation using the missing indicator method. The multilevel least absolute selection and shrinkage operator (LASSO) regression was used to select predictors into the final multilevel logistic models. Three measures, the area under the receiver operating characteristic curve (AUROC) and precision-recall curve (AUPRC) and calibration curves, were used to assess the predictive performance of the models. RESULTS: The selected-in factors in the final models, using LASSO regression, are related to pre- and intra-treatment clinical symptoms and pain experience. Predictive performance of the models remained the same with the inclusion (exclusion) of the socio-demographic factors. For predicting one-week outcome, the model built with combined set of predictors yielded the highest AUROC and AUPRC of 0.85 and 0.72, followed by the models built with clinical factors (AUROC = 0.82, AUPRC = 0.66). The lowest predictive ability was found in models with only sociodemographic characteristics (AUROC = 0.68, AUPRC = 0.40). Similar patterns were observed in predicting six-month outcome, where the AUROC for models with combined, clinical and sociodemographic sets of predictors were 0.85, 0.89 and 0.66, respectively, and the AUPRC were 0.48, 0.53 and 0.22, respectively. CONCLUSIONS: Clinical factors such as the severity and experience of pre-operative and intra-operative pain were discovered important to the subsequent development of pain following RCTs. Adding sociodemographic characteristics to the models with clinical factors did not change the models' predictive performance or the proportion of explained variance.

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Polymer-protein hybrids can be deployed to improve protein solubility and stability in denaturing environments. While previous work used robotics and active machine learning to inform new designs, further biophysical information is required to ascertain structure-function behavior. Here, we show the value of tandem small-angle x-ray scattering (SAXS) and quartz crystal microbalance with dissipation (QCMD) experiments to reveal detailed polymer-protein interactions with horseradish peroxidase (HRP) as a test case. Of particular interest was the process of polymer-protein complex formation under thermal stress whereby SAXS monitors formation in solution while QCMD follows these dynamics at an interface. The radius of gyration (Rg ) of the protein as measured by SAXS does not change significantly in the presence of polymer under denaturing conditions, but thickness and dissipation changes were observed in QCMD data. SAXS data with and without thermal stress were utilized to create bead models of the potential complexes and denatured enzyme, and each model fit provided insight into the degree of interactions. Additionally, QCMD data demonstrated that HRP deforms by spreading upon surface adsorption at low concentration as shown by longer adsorption times and smaller frequency shifts. In contrast, thermally stressed and highly inactive HRP had faster adsorption kinetics. The combination of SAXS and QCMD serves as a framework for biophysical characterization of interactions between proteins and polymers which could be useful in designing polymer-protein hybrids.

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Injuries to the nervous system present formidable challenges to scientists, clinicians, and patients. While regeneration within the central nervous system is minimal, peripheral nerves can regenerate, albeit with limitations. The regenerative mechanisms of the peripheral nervous system thus provide fertile ground for clinical and scientific advancement, and opportunities to learn fundamental lessons regarding nerve behavior in the context of regeneration, particularly the relationship of axons to their support cells and the extracellular matrix environment. However, few current interventions adequately address peripheral nerve injuries. This article aims to elucidate areas in which progress might be made toward developing better interventions, particularly using synthetic nerve grafts. The article first provides a thorough review of peripheral nerve anatomy, physiology, and the regenerative mechanisms that occur in response to injury. This is followed by a discussion of currently available interventions for peripheral nerve injuries. Promising biomaterial fabrication techniques which aim to recapitulate nerve architecture, along with approaches to enhancing these biomaterial scaffolds with growth factors and cellular components, are then described. The final section elucidates specific considerations when developing nerve grafts, including utilizing induced pluripotent stem cells, Schwann cells, nerve growth factors, and multilayered structures that mimic the architectures of the natural nerve.

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Parkinson's disease (PD) affects 1-2% of people over 65, causing significant morbidity across a progressive disease course. The classic PD motor deficits are caused by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in the loss of their long-distance axonal projections that modulate striatal output. While contemporary treatments temporarily alleviate symptoms of this disconnection, there is no approach able to replace the nigrostriatal pathway. We applied microtissue engineering techniques to create a living, implantable tissue-engineered nigrostriatal pathway (TE-NSP) that mimics the architecture and function of the native pathway. TE-NSPs comprise a discrete population of dopaminergic neurons extending long, bundled axonal tracts within the lumen of hydrogel micro-columns. Neurons were isolated from the ventral mesencephalon of transgenic rats selectively expressing the green fluorescent protein in dopaminergic neurons with subsequent fluorescent-activated cell sorting to enrich a population to 60% purity. The lumen extracellular matrix and growth factors were varied to optimize cytoarchitecture and neurite length, while immunocytochemistry and fast-scan cyclic voltammetry (FSCV) revealed that TE-NSP axons released dopamine and integrated with striatal neurons in vitro. Finally, TE-NSPs were implanted to span the nigrostriatal pathway in a rat PD model with a unilateral 6-hydroxydopamine SNpc lesion. Immunohistochemistry and FSCV established that transplanted TE-NSPs survived, maintained their axonal tract projections, extended dopaminergic neurites into host tissue, and released dopamine in the striatum. This work showed proof of concept that TE-NSPs can reconstruct the nigrostriatal pathway, providing motivation for future studies evaluating potential functional benefits and long-term durability of this strategy. This pathway reconstruction strategy may ultimately replace lost neuroarchitecture and alleviate the cause of motor symptoms for PD patients.

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Poly(ethylene glycol), PEG, known to inhibit protein adsorption, is widely used on the surfaces of biomedical devices when biofilm formation is undesirable. Poly(desaminotyrosyl-tyrosine ethyl ester carbonate), PDTEC, PC for short, has been a promising coating polymer for insertion devices, and it has been anticipated that PEG plays a similar role if it is copolymerized with PC. Earlier studies show that no fibrinogen (Fg) is adsorbed onto PC polymers with PEG beyond the threshold weight percentage. This is attributed to the phase separation of PEG. Further, iodination of the PC units in the PC polymer, (I2PC), has been found to counteract this Fg-repulsive effect by PEG. In this study, we employ surface-sensitive X-ray techniques to demonstrate the surface affinity of Fg toward the air-water interface, particularly in the presence of self-assembled PC-based film, in which its constituent polymer units are assumed to be much more mobile as a free-standing film. Fg is found to form a Gibbs monolayer with its long axis parallel to the aqueous surface, thus maximizing its interactions with hydrophobic interfaces. It influences the amount of insoluble, surface-bound I2PC likely due to the desorption of the formed Fg-I2PC complex and/or the penetration of Fg onto the I2PC film. The results show that the phase behavior at the liquid-polymer interface shall be taken into account for the surface behavior of bulk polymers surrounded by tissue. The ability of PEG units rearranging into a protein-blocking layer, rather than its mere presence in the polymer, is the key to antifouling characteristics desired for polymeric coating on insertion devices.

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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.