Chestnut-Inspired Hollow Hydroxyapatite 3D Printing Scaffolds Accelerate Bone Regeneration by Recruiting Calcium Ions and Regulating Inflammation.

This study aims to overcome the drawbacks associated with hydroxyapatite (HAP) dense structures after sintering, which often result in undesirable features such as large grain size, reduced porosity, high crystallinity, and low specific surface area. These characteristics hinder osseointegration and limit the clinical applicability of the material. To address these issues, a new method involving the preparation of hollow hydroxyapatite (hHAP) microspheres has been proposed. These microspheres exhibit distinctive traits including weak crystallization, high specific surface area, and increased porosity. The weak crystallization aligns more closely with early mineralization products found in the human body and animals. Moreover, the microspheres' high specific surface area and porosity offer advantages for protein loading and facilitating osteoblast attachment. This innovative approach not only mitigates the limitations of conventional HAP structures but also holds the potential for improving the effectiveness of hydroxyapatite in biomedical applications, particularly in enhancing osseointegration. Three-dimensional printed hHAP/chitosan (CS) scaffolds with different hHAP concentration gradients were manufactured, and the physical and biological properties of each group were systematically evaluated. In vitro and in vivo experiments show that the hHAP/CS scaffold has excellent performance in bone remodeling. Furthermore, in-scaffold components, hHAP and CS were cocultured with bone marrow mesenchymal stem cells to explore the regulatory role of hHAP and CS in the process of bone healing and to reveal the cell-level specific regulatory network activated by hHAP. Enrichment analysis showed that hHAP can promote bone regeneration and reconstruction by recruiting calcium ions and regulating inflammatory reactions.

DLP fabrication of HA scaffold with customized porous structures to regulate immune microenvironment and macrophage polarization for enhancing bone regeneration.

The immune microenvironment plays a pivotal role in osteoanagenesis. Biomaterials can modulate osteogenic efficacy by inducing specific local immune reactions. As 3D-printing technology advances, digital light projection printing has emerged as a promising method for creating large scale, high-precision biomaterial scaffolds. By adjusting the solid content and the sintering conditions during printing, the pore size of biomaterials can be meticulously controlled. Yet, the systematic influence of pore size on the immune microenvironment remains uncharted. We fabricated 3D-printed hydroxyapatite bioceramic scaffolds with three distinct pore sizes: 400 µm, 600 µm, and 800 µm. Our study revealed that scaffolds with a pore size of 600 µm promote macrophage M2 polarization, which is achieved by upregulating interferon-beta and HIF-1α production. When these materials were implanted subcutaneously in rats and within rabbit skulls, we observed that the 600 µm scaffolds notably improved the long-term inflammatory response, fostered vascular proliferation, and augmented new bone growth. This research paves the way for innovative therapeutic strategies for treating large segmental bone defects in clinical settings.

Consistent long-term practice leads to consistent improvement: Benefits of self-managed therapy for language and cognitive deficits using a digital therapeutic.

Background: Although speech-language therapy (SLT) is proven to be beneficial to recovery of post-stroke aphasia, delivering sufficiently high amounts of dosage remains a problem in real-world clinical practice. Self-managed SLT was introduced to solve the problem. Previous research showed in a 10-week period, increased dosage frequency could lead to better performance, however, it is uncertain if dosage still affects performance over a longer period of practice time and whether gains can be seen following practice over several months. Objective: This study aims to evaluate data from a health app (Constant Therapy) to investigate the relationship between dosage amount and improvements following a 30-week treatment period. Two cohorts of users were analyzed. One was comprised of patients with a consistent average weekly dosage amount and the other cohort was comprised of users whose practice had higher variability. Methods: We conducted two analyses with two cohorts of post-stroke patients who used Constant Therapy. The first cohort contains 537 "consistent" users, while the second cohort contains 2,159. The 30-week practice period was split into three consecutive 10-week practice windows to calculate average dosage amount. In each 10-week practice period, patients were grouped by their average dosage into low (0-15 min/week), medium (15-40 min/week) and moderate dosage (greater than 40 min/week) groups. Linear mixed-effects models were employed to evaluate if dosage amount was a significant factor affecting performance. Pairwise comparison was also applied to evaluate the slope difference between groups. Results: For the consistent cohort, medium (ß = .002, t 17,700 = 7.64, P < .001) and moderate (ß = .003, t 9,297 = 7.94, P < .001) dosage groups showed significant improvement compared to the low dosage group. The moderate group also showed greater improvement compared to the medium group. For the variable cohort in analysis 2, the same trend was shown in the first two 10-week windows, however, in weeks 21-30, the difference was insignificant between low and medium groups (ß = .001, t = 1.76, P = .078). Conclusions: This study showed a higher dosage amount is related to greater therapy outcomes in over 6 months of digital self-managed therapy. It also showed that regardless of the exact pattern of practice, self-managed SLT leads to significant and sustained performance gains.