Biological Scaffolds Research Articles

Design and optimization of 3D-bioprinted cell-laden scaffolds in dynamic culture

Light-based 3D printing enables the fabrication of biological scaffolds with high precision, versatility and biocompatibility, particularly the cell-laden scaffolds with architecturally complex geometric features. However, many bioprinted tissue scaffolds suffer from low cell viability due to insufficient oxygen and nutrient supply, which is heavily influenced by scaffold structure and cultivation conditions. Current practice relies mainly on resource-intensive trial-and-error methods to optimize scaffolds’ structures and cultivation parameters. In this study, we developed a comprehensive multi-physics model integrating fluid dynamics, oxygen mass transfer, cell oxygen consumption, and cell growth processes to capture cell growth behaviors in scaffolds, establishing a robust theoretical foundation for scaffold structure optimization. The modeling results showed that a large number of parameters, such as system inlet flow rate, geometric feature size, cell parameters, and material properties, significantly impact oxygen concentration and cell growth within the scaffold. A two-step optimization strategy is proposed in this paper and was applied to obtain optimal geometric parameters of channeled scaffolds to demonstrate the model’s effectiveness for scaffold optimization. The model can be employed for scaffolds with arbitrary shapes and various materials, facilitating the optimal design of sophisticated scaffolds for more advanced tissue engineering.

Hot spots and frontiers in bone-tendon interface research: a bibliometric analysis and visualization from 2000 to 2023.

In this research, we investigated the current status, hotspots, frontiers, and trends of research in the field of bone-tendon interface (BTI) from 2000 to 2023, based on bibliometrics and visualization and analysis in CiteSpace, VOSviewer, and a bibliometric package in R software. We collected and organized the papers in the Web of Science core collection (WoSCC) for the past 23 years (2000-2023), and extracted and analyzed the papers related to BTI. The extracted papers were bibliometrically analyzed using CiteSpace for overall publication trends, authors, countries/regions, journals, keywords, research hotspots, and frontiers. A total of 1,995 papers met the inclusion criteria. The number of papers published and the number of citations in the field of BTI have continued to grow steadily over the past 23 years. In terms of research contribution, the United States leads in terms of the number and quality of publications, number of citations, and collaborations with other countries, while the United Kingdom and the Netherlands lead in terms of the average number of citations. The University of Leeds publishes the largest number of papers, and among the institutions hosting the 100 most cited papers Hospital for Special Surgery takes the top spot. MCGONAGLE D has published the highest number of papers (73) in the last 10 years. The top three clusters include #0 "psoriatic arthritis", #1 "rotator cuff repair", and #2 "tissue engineering". The structure and function of the BTI and its key mechanisms in the healing process are the key to research, while new therapies such as mechanical stimulation, platelet-rich plasma, mesenchymal stem cells, and biological scaffolds are hot topics and trends in research. Over the past 23 years, global research on the BTI has expanded in both breadth and depth. The focus of research has shifted from studies concentrating on the structure of the BTI and the disease itself to new therapies such as biomaterial-based alternative treatments, mechanical stimulation, platelet-rich plasma, etc.

Strategies for decellularization, re-cellularIzation and crosslinking in liver bioengineering.

Liver transplantation is the only definitive treatment for end-stage liver disease and its availability is restricted by organ donor shortages. The development of liver bioengineering provides the probability to create a functional alternative to reduce the gap in organ demand and supply. Decellularized liver scaffolds have been widely applied in bioengineering because they can mimic the native liver microenvironment and retain extracellular matrix (ECM) components. Multiple approaches including chemical, physical and biological methods have been developed for liver decellularization in current studies, but a full set of unified criteria has not yet been established. Each method has its advantages and drawbacks that influence the microstructure and ligand landscape of decellularized liver scaffolds. Optimizing a decellularization method to eliminate cell material while retaining as much of the ECM intact as possible is therefore important for biological scaffold applications. Furthermore, crosslinking strategies can improve the biological performance of scaffolds, including reinforcing biomechanics, delaying degradation in vivo and reducing immune rejection, which can better promote the integration of re-cellularized scaffolds with host tissue and influence the reconstruction process. In this review, we aim to present the different liver decellularization techniques, the crosslinking methods to improve scaffold characteristics with crosslinking and the preparation of soluble ECM.

Research advances on stem cell-based treatments in animal studies and clinical trials of lymphedema

To summarize the progress of the roles and mechanisms of various types of stem cell-based treatments and their combination therapies in both animal studies and clinical trials of lymphedema. The literature on stem cell-based treatments for lymphedema in recent years at home and abroad was extensively reviewed, and the animal studies and clinical trials on different types of stem cells for lymphedema were summarized. Various types of stem cells have shown certain effects in animal studies and clinical trials on the treatment of lymphedema, mainly through local differentiation into lymphoid endothelial cells and paracrine cytokines with different functions. Current research focuses on two cell types, adipose derived stem cells and bone marrow mesenchymal stem cells, both of which have their own advantages and disadvantages, mainly reflected in the therapeutic effect of stem cells, the difficulty of obtaining stem cells and the content in vivo. In addition, stem cells can also play a synergistic role in combination with other treatments, such as conservative treatment, surgical intervention, cytokines, biological scaffolds, and so on. However, it is still limited to the basic research stage, and only a small number of studies have completed clinical trials. Stem cells have great transformation potential in the treatment of lymphedema, but there is no unified standard in the selection of cell types, the amount of transplanted cells, and the timing of transplantation.

Chemical and Structural Engineering of Gelatin-Based Delivery Systems for Therapeutic Applications: A Review.

As a biodegradable and biocompatible protein derived from collagen, gelatin has been extensively exploited as a fundamental component of biological scaffolds and drug delivery systems for precise medicine. The easily engineered gelatin holds great promise in formulating various delivery systems to protect and enhance the efficacy of drugs for improving the safety and effectiveness of numerous pharmaceuticals. The remarkable biocompatibility and adjustable mechanical properties of gelatin permit the construction of active 3D scaffolds to accelerate the regeneration of injured tissues and organs. In this Review, we delve into diverse strategies for fabricating and functionalizing gelatin-based structures, which are applicable to gene and drug delivery as well as tissue engineering. We emphasized the advantages of various gelatin derivatives, including methacryloyl gelatin, polyethylene glycol-modified gelatin, thiolated gelatin, and alendronate-modified gelatin. These derivatives exhibit excellent physicochemical and biological properties, allowing the fabrication of tailor-made structures for biomedical applications. Additionally, we explored the latest developments in the modulation of their physicochemical properties by combining additive materials and manufacturing platforms, outlining the design of multifunctional gelatin-based micro-, nano-, and macrostructures. While discussing the current limitations, we also addressed the challenges that need to be overcome for clinical translation, including high manufacturing costs, limited application scenarios, and potential immunogenicity. This Review provides insight into how the structural and chemical engineering of gelatin can be leveraged to pave the way for significant advancements in biomedical applications and the improvement of patient outcomes.

Application of metal-organic frameworks-based functional composite scaffolds in tissue engineering.

With the rapid development of materials science and tissue engineering, a variety of biomaterials have been used to construct tissue engineering scaffolds. Due to the performance limitations of single materials, functional composite biomaterials have attracted great attention as tools to improve the effectiveness of biological scaffolds for tissue repair. In recent years, metal-organic frameworks (MOFs) have shown great promise for application in tissue engineering because of their high specific surface area, high porosity, high biocompatibility, appropriate environmental sensitivities and other advantages. This review introduces methods for the construction of MOFs-based functional composite scaffolds and describes the specific functions and mechanisms of MOFs in repairing damaged tissue. The latest MOFs-based functional composites and their applications in different tissues are discussed. Finally, the challenges and future prospects of using MOFs-based composites in tissue engineering are summarized. The aim of this review is to show the great potential of MOFs-based functional composite materials in the field of tissue engineering and to stimulate further innovation in this promising area.

Isocyanide-based multicomponent reactions for the synthesis of benzopyran derivatives with biological scaffolds.

Benzopyrans (BZPs) are among the most privileged and influential small O-heterocycles that form the core of many natural compounds, commercial drugs, biological compositions, agrochemicals, and functional materials. BZPs are divided into six general categories including coumarins, chromans, 2H-chromenes, 4H-chromenes, chromones, and 4-chromanones, each of which is abundant in many plants and foods. These oxygenated heterocyclic compounds are fascinating motifs and have extensive applications in biology and materials science. Hence, numerous efforts have been made to develop innovative approaches for their extraction and synthesis. However, most of them are step-by-step or multi-step strategies that suffer from waste material generation and a tedious extraction process. Isocyanide-based multicomponent reactions (I-MCRs) offer a highly efficient method for overcoming these problems. The I-MCR is a simple and environmentally friendly one-pot domino procedure that does not require intermediate isolation or workup and is generally more efficient in material usage. This review covers all research articles related to I-MCRs for synthesizing BZP derivatives from the beginning to the middle of the year 2023. This strategy will be useful for organic and pharmaceutical chemists to design new drugs and optimize the synthesis steps of biological compounds and commercial drugs with benzopyran cores.

The effect of injectable platelet-rich fibrin and platelet-rich fibrin in regenerative endodontics: a comparative in vitro study.

To explore the feasibility of injectable platelet-rich fibrin (i-PRF) in regenerative endodontics by comparing the effect of i-PRF and platelet-rich fibrin (PRF) on the biological behavior and angiogenesis of human stem cells from the apical papilla (SCAPs). i-PRF and PRF were obtained from venous blood by two different centrifugation methods, followed by hematoxylin-eosin (HE) staining and scanning electron microscopy (SEM). Enzyme-linked immunosorbent assay (ELISA) was conducted to quantify the growth factors. SCAPs were cultured with different concentrations of i-PRF extract (i-PRFe) and PRF extract (PRFe), and the optimal concentrations were selected using the Cell Counting Kit-8 (CCK-8) assay. The cell proliferation and migration potentials of SCAPs were then observed using the CCK-8 and Transwell assays. Mineralization ability was detected by alizarin red staining (ARS), and angiogenesis ability was detected by tube formation assay. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to evaluate the expression of genes related to mineralization and angiogenesis. The data were subjected to statistical analysis. i-PRF and PRF showed a similar three-dimensional fibrin structure, while i-PRF released a higher concentration of growth factors than PRF ( P <.05). 1/4× i-PRFe and 1/4× PRFe were selected as the optimal concentrations. The cell proliferation rate of the i-PRFe group was higher than that of the PRFe group ( P <.05), while no statistical difference was observed between them in terms of cell mitigation ( P >.05). More importantly, our results showed that i-PRFe had a stronger effect on SCAPs than PRFe in facilitating mineralization and angiogenesis, with the consistent result of RT-qPCR ( P <.05). This study revealed that i-PRF released a higher concentration of growth factors and was superior to PRF in promoting proliferation, mineralization and angiogenesis of SCAPs, which indicates that i-PRF could be a promising biological scaffold for application in pulp regeneration.

Graphene Oxide Quantum Dots-Preactivated Dental Pulp Stem Cells/GelMA Facilitates Mitophagy-Regulated Bone Regeneration.

In bone tissue engineering (BTE), cell-laden scaffolds offer a promising strategy for repairing bone defects, particularly when host cell regeneration is insufficient due to age or disease. Exogenous stem cell-based BTE requires bioactive factors to activate these cells. Graphene oxide quantum dots (GOQDs), zero-dimensional derivatives of graphene oxide, have emerged as potential osteogenic nanomedicines. However, constructing biological scaffolds with GOQDs and elucidating their biological mechanisms remain critical challenges. We utilized GOQDs with a particle size of 10 nm, characterized by a surface rich in C-O-H and C-O-C functional groups. We developed a gelatin methacryloyl (GelMA) hydrogel incorporated with GOQDs-treated dental pulp stem cells (DPSCs). These constructs were transplanted into rat calvarial bone defects to estimate the effectiveness of GOQDs-induced DPSCs in repairing bone defects while also investigating the molecular mechanism underlying GOQDs-induced osteogenesis in DPSCs. GOQDs at 5μg/mL significantly enhanced the osteogenic differentiation of DPSCs without toxicity. The GOQDs-induced DPSCs showed active osteogenic potential in three-dimensional cell culture system. In vivo, transplantation of GOQDs-preactivated DPSCs/GelMA composite effectively facilitated calvarial bone regeneration. Mechanistically, GOQDs stimulated mitophagy flux through the phosphatase-and-tensin homolog-induced putative kinase 1 (PINK1)/Parkin E3 ubiquitin ligase (PRKN) pathway. Notably, inhibiting mitophagy with cyclosporin A prevented the osteogenic activity of GOQDs. This research presents a well-designed bionic GOQDs/DPSCs/GelMA composite scaffold and demonstrated its ability to promote bone regeneration by enhancing mitophagy. These findings highlight the significant potential of this composite for application in BTE and underscore the crucial role of mitophagy in promoting the osteogenic differentiation of GOQDs-induced stem cells.

Hyperspectral Tracking of In Situ Tissue Regeneration and Remodeling in a Rationally Designed Biological Scaffold in a Rat Subcutaneous Model

Hyperspectral Tracking of In Situ Tissue Regeneration and Remodeling in a Rationally Designed Biological Scaffold in a Rat Subcutaneous Model

Revascularization in Immature Permanent Teeth - A Case Series

Immature permanent teeth with developing, root apices with dental pulp infections resulting from caries or trauma represent a formidable clinical challenge. Biologically based principles of regenerative endodontic procedures in the treatment of immature, necrotic teeth have replaced the traditional ‘apexification’ procedures. The purpose of this case series was to investigate the outcome of the pulpal revascularization procedure on immature permanent teeth with or without apical periodontitis. The case series comprised 3 patients (8–11 years of age), consisting of 4 incisors and 1 premolar with incompletely formed apex with or without signs or symptoms of periapical pathology. Induction of blood clot was the technique selected for root closure if the tooth was asymptomatic following the placement of intracanal antibiotic paste for 3 weeks. Apexification was initiated if the tooth remains symptomatic. Out of the five teeth revascularisation was successful, and continued root-end closure was obtained in four teeth. One tooth remained symptomatic and apexification was initiated. One patient failed to follow up for the study. Revascularisation by induction of apical bleeding is a potential source of stem cells for the continued root maturation and it creates a blood clot that would act as a biologic scaffold for the recruited stem cells.

Age-associated Senescent - T Cell Signaling Promotes Type 3 Immunity that Inhibits the Biomaterial Regenerative Response.

Aging is associated with immunological changes that compromise response to infections and vaccines, exacerbate inflammatory diseases and can potentially mitigate tissue repair. Even so, age-related changes to the immune response to tissue damage and regenerative medicine therapies remain unknown. Here, it is characterized how aging induces changes in immunological signatures that inhibit tissue repair and therapeutic response to a clinical regenerative biological scaffold derived from extracellular matrix. Signatures of inflammation and interleukin (IL)-17 signaling increased with injury and treatment both locally and regionally in aged animals, and computational analysis uncovered age-associated senescent-T cell communication that promotes type 3 immunity in T cells. Local inhibition of type 3 immune activation using IL17-neutralizing antibodies improves healing and restores therapeutic response to the regenerative biomaterial, promoting muscle repair in older animals. These results provide insights into tissue immune dysregulation that occurs with aging that can be targeted to rejuvenate repair.

Magnetic Field Intervention Enhances Cellular Migration Rates in Biological Scaffolds.

The impact of magnetic fields on cellular function is diverse but can be described at least in part by the radical pair mechanism (RPM), where magnetic field intervention alters reactive oxygen species (ROS) populations and downstream cellular signaling. Here, cellular migration within three-dimensional scaffolds was monitored in an applied oscillating 1.4 MHz radiofrequency (RF) magnetic field with an amplitude of 10 µT and a static 50 µT magnetic field. Given that cellular bioenergetics can be altered based on applied RF magnetic fields, this study focused on a magnetic field configuration that increased cellular respiration. Results suggest that RF accelerated cell clustering and elongation after 1 day, with increased levels of clustering and cellular linkage after 7 days. Cell distribution analysis within the scaffolds revealed that the clustering rate during the first day was increased nearly five times in the RF environment. Electron microscopy provided additional topological information and verified the development of fibrous networks, with a cell-derived matrix (CDM) visualized after 7 days in samples maintained in RF. This work demonstrates time-dependent cellular migration that may be influenced by quantum biology (QB) processes and downstream oxidative signaling, enhancing cellular migration behavior.

Porous mullite ceramics with hierarchical pores constructed via vat photopolymerization of multi-phase Pickering emulsion

Herein, a novel method for hierarchically porous mullite ceramics with complex and fine structure was proposed, that is vat photopolymerization of multi-phase Pickering emulsion. Pickering emulsions stabilized by mixed particles features water in oil type, high solid content, suitable rheological properties and excellent ultraviolet-curing ability, making them appropriate pastes for vat photopolymerization. The printed components possess hierarchically porous structure involving interconnected mm-scale pores designed by three-dimensional model, uniform μm-scale pores derived from emulsion droplets and less voids generated by the removal of photosensitive resin in the location of continuous phase. Therefore, porous mullite ceramics with octet lattice structure possess excellent compressive strength up to 4.3 MPa at high porosity of 74.08% compared to the counterparts from pure resin-based suspension. The products from this facile, universal and effective method could serve as ideal candidates for catalytic filters, biological scaffolds and electronic components owing to their designable structure and outstanding multifunctionality.

Individualized bio-scaffold encapsulating siPTEN-loaded exosomes for promoting neuronal regeneration in spinal cord injury

Biological scaffold implants loaded with exosomes were acknowledged as a promising strategy for the treatment of spinal cord injury. In this study, we constructed an individualized biomimetic scaffold based on combination of multimodal imaging and 3D printing technology, featuring sustained release, biodegradability, and strongly biocompatibility. The scaffold incorporated mesenchymal stem cell-derived exosomes to alleviate inflammatory response in microenvironment and reduce scar formation of ECM molecule deposition. Furthermore, to effectively enhance neuronal repair and regeneration, siRNAs targeting PTEN were introduced into exosomes. The engineered exosomes within scaffold induced endogenous neuronal regeneration and enhanced axonal growth through PTEN/PI3K/AKT/mTOR signaling pathway. Additionally, implantation of scaffold could bridge the severed ends, thus providing spatial signals to modulate the organization of neural cells, facilitating the reconstruction of complex neural networks, and restoring nerve conduction. Collectively, the individualized 3D printed bio-scaffold encapsulated siPTEN-loaded exosomes could offer great promise for the prospective clinical translation in spinal cord injury therapy.

Evaluation of a decellularized bronchial patch transplant in a porcine model

Biological scaffolds for airway reconstruction are an important clinical need and have been extensively investigated experimentally and clinically, but without uniform success. In this study, we evaluated the use of a decellularized bronchus graft for airway reconstruction. Decellularized left bronchi were procured from decellularized porcine lungs and utilized as grafts for airway patch transplantation. A tracheal window was created and the decellularized bronchus was transplanted into the defect in a porcine model. Animals were euthanized at 7 days, 1 month, and 2 months post-operatively. Histological analysis, immunohistochemistry, scanning electron microscopy, and strength tests were conducted in order to evaluate epithelialization, inflammation, and physical strength of the graft. All pigs recovered from general anesthesia and survived without airway obstruction until the planned euthanasia timepoint. Histological and electron microscopy analyses revealed that the decellularized bronchus graft was well integrated with native tissue and covered by an epithelial layer at 1 month. Immunostaining of the decellularized bronchus graft was positive for CD31 and no difference was observed with immune markers (CD3, CD11b, myeloperoxidase) at two months. Although not significant, tensile strength was decreased after one month, but recovered by two months. Decellularized bronchial grafts show promising results for airway patch reconstruction in a porcine model. Revascularization and re-epithelialization were observed and the immunological reaction was comparable with the autografts. This approach is clinically relevant and could potentially be utilized for future applications for tracheal replacement.

Role of antimicrobial coated allogenic dried amniotic membrane in partial thickness burns

Objectives: Human amniotic membrane (HAM) is the biological scaffold for burn wound management. Allogenic HAM helps in promoting the healing of partial-thickness burn wounds. In this case study, we share our experience in using the antimicrobial-coated HAM. Material and Methods: The subject was an 8-year-old male child, who had accidental electrocution while playing near the electrical transformer and developed second-degree superficial and deep burns over the chest, abdomen, and bilateral lower limb. The child underwent tangential excision of the deep burns, and partial thickness burns are covered with dried allogenic HAM. Results: Intraoperative and postoperative periods were uneventful for the patient. The raw area took up the AM well, and burn wounds healed well in the second-degree superficial burns. A deep burns wound bed was prepared, and split skin grafting was done to the raw area. The wounds healed well after two weeks with minimal scarring. No complications or side effects were noted. Conclusion: Allogenic HAM plays a role in burn wound healing in burns. It helps in promoting the wound healing process.

Bioengineered Small-Diameter Vascular Xenografts as an Alternative to Autologous Vascular Grafting for Emergency Revascularization – a Preliminary Study

Abstract Background Autologous vascular arterial or venous graft are not available in 10-40% of patients, due to vascular pathologies, and the utility of decellularized biological scaffolds would be a solution for those cases. The purpose of this research was to obtain a functional acellular xenograft, prior to in-vivo testing as a vascular graft in an experimental animal. Materials and method Two batches of carotid vasculo-nervous bundles were collected from porcine models from a local slaughterhouse. The arterial grafts were dissected and isolated, obtaining carotid arteries with a caliber of 5–6 mm and a length of approximately 10–12 cm. Two decellularization protocols were used, immersion (n = 10) and perfusion (n = 9). The resulting grafts underwent histological examination, DNA analysis, electrophoresis and spectrophotometry. Results Due to severe tissue damage and friability, the batch that was decellularized using perfusion was not examined. The histological examination of grafts stained with hematoxylin-eosin and DAPI highlighted the absence of nuclei. Spectrophotometry revealed a 90% decellularization, and electrophoresis of revealed the migration band of the material extracted from the fresh tissue, as well as the absence of migration bands in the case of the material extracted from decellularized tissues. Conclusion We successfully used the immersion protocol to obtain a functional acellular vascular graft, in contrast to perfusion decellularization, where intraluminal high pressures damage the extracellular matrix.

Enhancing decellularized vascular scaffolds with PVDF and PCL reinforcement: a fused deposition modeling approach

BackgroundDecellularized xenogenic scaffolds represent a promising substrate for tissue-engineered vascular prostheses, particularly those with smaller diameters (&amp;lt;6 mm). Despite their benefits, a notable limitation presents itself during decellularization, namely, the diminished mechanical strength that introduces the risk of aneurysmal dilations in the early post-implantation period. This study introduces a strategy for modification the mechanical properties of these biological scaffolds through the forming of an external polymeric reinforcement via thermal extrusion.MethodsThe study utilized scaffolds fabricated from bovine internal mammary arteries through decellularization and preservation. The scaffolds were divided into subgroups and reinforced with polymeric helices made of Polyvinylidene fluoride (PVDF) and Polycaprolactone (PCL), n = 5 for each. An experimental setup for external reinforcement coating was designed. Computed microtomography was employed to obtain accurate 3D models of the scaffolds. Mechanical properties were evaluated through in vitro uniaxial tension tests (Z50, Zwick/Roell, Germany), compliance evaluation and numerical simulations (Abaqus/CAE, Dassault Systemes, France) to investigate the effect of external reinforcement on aneurysm growth.ResultsUsing a double-layer helix for the reinforcement significantly enhanced the radial tensile strength of the scaffolds, increasing it up to 2.26 times. Yet, the comparison of vessel's compliance between two reinforced and the Control scaffolds within the physiological pressures range did not reveal any significant differences. Numerical simulation of aneurysm growth showed that thin-walled regions of the Control scaffold developed aneurysmal-type protrusions, bulging up to 0.7 mm, with a substantial degradation of mechanical properties. In contrast, both PVDF and PCL reinforced scaffolds did not exhibit significant property degradation, with deformations ranging 0.1–0.13 mm depending on the model, and a maximum decrease in the modulus of elasticity of 23%.ConclusionThe results of the study demonstrated that the external polymer helical reinforcement of decellularized scaffolds via thermal extrusion enables a controlled modification of mechanical properties, notably enhancing radial strength while maintaining sufficient compliance within the physiological pressure range. A series of in vitro tests demonstrated the consistency and potential of this approach for decellularized xenogenic scaffolds, a concept that had not been explored before.

Shish-kebab structure fiber with nano and micro diameter regulate macrophage polarization for anti-inflammatory and bone differentiation

Biopolymer grafts often have limited biocompatibility, triggering excessive inflammatory responses similar to foreign bodies. Macrophage phenotype shifts are pivotal in the inflammatory response and graft success. The effects of the morphology and physical attributes of the material itself on macrophage polarization should be the focus. In this study, we prepared electrospun fibers with diverse diameters and formed a shish-kebab (SK) structure on the material surface by solution-induced crystallization, forming electrospun fiber scaffolds with diverse pore sizes and roughness. In vitro cell culture experiments demonstrated that SK structure fibers could regulate macrophage differentiation toward M2 phenotype, and the results of in vitro simulation of in vivo tissue reconstruction by the microenvironment demonstrated that the paracrine role of M2 phenotype macrophages could promote bone marrow mesenchymal stem cells (BMSCs) to differentiate into osteoblasts. In rats implanted with a subcutaneous SK-structured fiber scaffold, the large-pore size and low-stiffness SK fiber scaffolds demonstrated superior immune performance, less macrophage aggregation, and easier differentiation to the anti-inflammatory M2 phenotype. Large pore sizes and low-stiffness SK fiber scaffolds guide the morphological design of biological scaffolds implanted in vivo, which is expected to be an effective strategy for reducing inflammation when applied to graft materials in clinical settings.