Optimization-based conformal path planning for in situ bioprinting during complex skin defect repair

The global demand for effective skin injury treatments has prompted the exploration of tissue engineering solutions.While three-dimensional(3D)bioprinting has shown promise,challenges persist with respect to achieving timely and compatible solutions to treat diverse skin injuries.In situ bioprinting has emerged as a key new technology,since it reduces risks during the implantation of printed scaffolds and demonstrates superior therapeutic effects.However,maintaining printing fidelity during in situ bioprinting remains a critical challenge,particularly with respect to model layering and path planning.This study proposes a novel optimization-based conformal path planning strategy for in situ bioprinting-based repair of complex skin injuries.This strategy employs constrained optimization to identify optimal waypoints on a point cloud-approximated curved surface,thereby ensuring a high degree of similarity between predesigned planar and surface-mapped 3D paths.Furthermore,this method is applicable for skin wound treatments,since it generates 3D-equidistant zigzag curves along surface tangents and enables multi-layer conformal path planning to facilitate the treatment of volumetric injuries.Furthermore,the proposed algorithm was found to be a feasible and effective treatment in a murine back injury model as well as in other complex models,thereby showcasing its potential to guide in situ bioprinting,enhance bioprinting fidelity,and facilitate improvement of clinical outcomes.

Concurrently bioprinted scaffolds with autologous bone and allogeneic BMSCs promote bone regeneration through native BMSC recruitment

Autologous bone marrow-derived mesenchymal stem cells(BMSCs)have been shown to promote osteogenesis;however,the effects of allogeneic BMSCs(allo-BMSCs)on bone regeneration remain unclear.Therefore,we explored the bone regeneration promotion effect of allo-BMSCs in 3D-printed autologous bone particle(ABP)scaffolds.First,we concurrently printed scaffolds with polycaprolactone,ABPs,and allo-BMSCs for appropriate support,providing bioactive factors and seed cells to promote osteogenesis.In vitro studies showed that ABP scaffolds promoted allo-BMSC osteogenic differentiation.In vivo studies revealed that the implantation of scaffolds loaded with ABPs and allo-BMSCs into canine skull defects for nine months promoted osteogenesis.Further experiments suggested that only a small portion of implanted allo-BMSCs survived and differentiated into vascular endothelial cells,chondrocytes,and osteocytes.The implanted allo-BMSCs released stromal cell-derived factor 1 through paracrine signaling to recruit native BMSCs into the defect,promoting bone regeneration.This study contributes to our understanding of allo-BMSCs,providing information relevant to their future application.

In vivo bioprinting:Broadening the therapeutic horizon for tissue injuries

Tissue injury is a collective term for various disorders associated with organs and tissues induced by extrinsic or intrinsic factors,which significantly concerns human health.In vivo bioprinting,an emerging tissue engineering approach,allows for the direct deposition of bioink into the defect sites inside the patient’s body,effectively addressing the challenges associated with the fabrication and implantation of irregularly shaped scaffolds and enabling the rapid on-site management of tissue injuries.This strategy complements operative therapy as well as pharmacotherapy,and broadens the therapeutic horizon for tissue injuries.The implementation of in vivo bioprinting requires targeted investigations in printing modalities,bioinks,and devices to accommodate the unique intracorporal microenvironment,as well as effective integrations with intraoperative procedures to facilitate its clinical application.In this review,we summarize the developments of in vivo bioprinting from three perspectives:modalities and bioinks,devices,and clinical integrations,and further discuss the current challenges and potential improvements in the future.

Vascularization ability of glioma stem cells in different three-dimensional microenvironments

Glioblastoma(GBM)is among the most common and aggressive adult central nervous system tumors.One prominent charac-teristic of GBM is the presence of abnormal microvessels.A significant correlation between angiogenesis and prognosis has been observed.Accurately reconstructing this neovascula-rization and tumor microenvironment through personalized in vitro disease models presents a significant challenge.However,it is crucial to develop new anti-angiogenic therapies for GBM.In this study,3D bioprinted glioma stem cell(GSC)-laden hydrogel scaffolds,hybrid Gsc hydrogels and ceil-free hydrogel scaffolds were manufactured to investigate the vas-cularization ability of GsCs in varying 3D microenvironments.

Enhanced burn wound healing by controlled-release 3D ADMSC-derived exosome-loaded hyaluronan hydrogel

Adipose mesenchymal stem cell(ADMSC)-derived exosomes(ADMSC-Exos)have shown great potential in regenerative medicine and been evidenced benefiting wound repair such as burns.However,the low yield,easy loss after direct coating,and no suitable loading system to improve their availability and efficacy hinder their clinical application for wound healing.And few studies focused on the comparison of biological functions between exosomes derived from different culture techniques,especially in exosome-releasing hydrogel system.Therefore,we designed a high-performance exosome controllable releasing hydrogel system for burn wound healing,namely loading 3D-printed microfiber culture-derived exosomes in a highly biocompatible hyaluronic acid(HA).In this project,we compared the biological functions in vitro and in a burn model among exosomes derived from the conventional two-dimensional(2D)plate culture(2D-Exos),microcarrier culture(2.5D-Exos),and 3D-printed microfiber culture(3D-Exos).Results showed that compared with 2D-Exos and 2.5D-Exos,3D-Exos promoted HACATs and HUVECs cell proliferation and migration more significantly.Additionally,3D-Exos had stronger angiogenesis-promoting effects in tube formation of(HUVECs)cells.Moreover,we found HA-loaded 3D-Exos showed better burn wound healing promotion compared to 2D-Exos and 2.5D-Exos,including accelerated burn wound healing rate and better collagen remodeling.The study findings reveal that the HA-loaded,controllable-release 3D-Exos repair system distinctly augments therapeutic efficacy in terms of wound healing,while concurrently introducing a facile application approach.This system markedly bolsters the exosomal loading efficiency,provides a robust protective milieu,and potentiates the inherent biological functionalities of the exosomes.Our findings provide a rationale for more efficient utilization of high-quality and high-yield 3D exosomes in the future,and a novel strategy for healing severe burns.