Treatment of bone-cartilage defects with dual-layer tissue-engineered scaffolds loaded with icariin and quercetin.

Over the past few decades, significant research has been conducted on tissue-engineered constructs for cartilage repair. However, there is a growing interest in addressing subchondral bone repair along with cartilage regeneration. This study focuses on a bilayer tissue engineering scaffold loaded with icariin (ICA) and quercetin (QU) for simultaneous treatment of knee joint cartilage and subchondral bone defects. The cytotoxicity of dual-layer scaffolds loaded with ICA and QU was assessed through live/dead cell staining. Subsequently, these dual-layer scaffolds loaded with ICA and QU were implanted into cartilage and subchondral bone defects in Sprague-Dawley (SD) rats. The repair effects were evaluated through macroscopic observation, computed tomography, and immunohistochemistry. After 12 weeks of implantation of dual-layer scaffolds loaded with ICA and QU into the cartilage and bone defects of SD rats, better repair effects were observed in both cartilage and bone defects compared to the blank control group. We found that the dual-layer tissue-engineered scaffold loaded with ICA and QU had excellent biocompatibility and could effectively repair articular cartilage and subchondral bone injuries, showing promising prospects for clinical applications.

An innovative intramedullary bone graft harvesting concept as a fundamental component of scaffold-guided bone regeneration: A preclinical in vivo validation.

Background: The deployment of bone grafts (BGs) is critical to the success of scaffold-guided bone regeneration (SGBR) of large bone defects. It is thus critical to provide harvesting devices that maximize osteogenic capacity of the autograft while also minimizing graft damage during collection. As an alternative to the Reamer-Irrigator-Aspirator 2 (RIA 2) system - the gold standard for large-volume graft harvesting used in orthopaedic clinics today - a novel intramedullary BG harvesting concept has been preclinically introduced and referred to as the ARA (aspirator + reaming-aspiration) concept. The ARA concept uses aspiration of the intramedullary content, followed by medullary reaming-aspiration of the endosteal bone. This concept allows greater customization of BG harvesting conditions vis-à-vis the RIA 2 system. Following its successful in vitro validation, we hypothesized that an ARA concept-collected BG would have comparable in vivo osteogenic capacity compared to the RIA 2 system-collected BG. Methods: We used 3D-printed, medical-grade polycaprolactone-hydroxyapatite (mPCL-HA, wt 96 %:4 %) scaffolds with a Voronoi design, loaded with or without different sheep-harvested BGs and tested them in an ectopic bone formation rat model for up to 8 weeks. Results: Active bone regeneration was observed throughout the scaffold-BG constructs, particularly on the surface of the bone chips with endochondral bone formation, and highly vascularized tissue formed within the fully interconnected pore architecture. There were no differences between the BGs derived from the RIA 2 system and the ARA concept in new bone volume formation and in compression tests (Young's modulus, p = 0.74; yield strength, p = 0.50). These results highlight that the osteogenic capacities of the mPCL-HA Voronoi scaffold loaded with BGs from the ARA concept and the RIA 2 system are equivalent. Conclusion: In conclusion, the ARA concept offers a promising alternative to the RIA 2 system for harvesting BGs to be clinically integrated into SGBR strategies. The translational potential of this article: Our results show that biodegradable composite scaffolds loaded with BGs from the novel intramedullary harvesting concept and the RIA 2 system have equivalent osteogenic capacity. Thus, the innovative, highly intuitive intramedullary harvesting concept offers a promising alternative to the RIA 2 system for harvesting bone grafts, which are an important component for the routine translation of SGBR concepts into clinical practice.

From electricity to vitality: the emerging use of piezoelectric materials in tissue regeneration.

The unique ability of piezoelectric materials to generate electricity spontaneously has attracted widespread interest in the medical field. In addition to the ability to convert mechanical stress into electrical energy, piezoelectric materials offer the advantages of high sensitivity, stability, accuracy and low power consumption. Because of these characteristics, they are widely applied in devices such as sensors, controllers and actuators. However, piezoelectric materials also show great potential for the medical manufacturing of artificial organs and for tissue regeneration and repair applications. For example, the use of piezoelectric materials in cochlear implants, cardiac pacemakers and other equipment may help to restore body function. Moreover, recent studies have shown that electrical signals play key roles in promoting tissue regeneration. In this context, the application of electrical signals generated by piezoelectric materials in processes such as bone healing, nerve regeneration and skin repair has become a prospective strategy. By mimicking the natural bioelectrical environment, piezoelectric materials can stimulate cell proliferation, differentiation and connection, thereby accelerating the process of self-repair in the body. However, many challenges remain to be overcome before these concepts can be applied in clinical practice, including material selection, biocompatibility and equipment design. On the basis of the principle of electrical signal regulation, this article reviews the definition, mechanism of action, classification, preparation and current biomedical applications of piezoelectric materials and discusses opportunities and challenges for their future clinical translation.

Drug delivery strategies through 3D-printed calcium phosphate.

3D printing has revolutionized bone tissue engineering (BTE) by enabling the fabrication of patient- or defect-specific scaffolds to enhance bone regeneration. The superior biocompatibility, customizable bioactivity, and biodegradability have enabled calcium phosphate (CaP) to gain significance as a bone graft material. 3D-printed (3DP) CaP scaffolds allow precise drug delivery due to their porous structure, adaptable structure-property relationship, dynamic chemistry, and controlled dissolution. The effectiveness of conventional scaffold-based drug delivery is hampered by initial burst release and drug loss. This review summarizes different multifunctional drug delivery approaches explored in controlling drug release, including polymer coatings, formulation integration, microporous scaffold design, chemical crosslinking, and direct extrusion printing for BTE applications. The review also outlines perspectives and future challenges in drug delivery research, paving the way for next-generation bone repair methodologies.

Electrospun fibrillary scaffold for electrochemical cell biomarkers detection.

A novel scaffold for in situ electrochemical detection of cell biomarkers was developed using electrospun nanofibers and commercial adhesive polymeric membranes. The electrochemical sensing of cell biomarkers requires the cultivation of the cells on/near the (bio)sensor surface in a manner to preserve an appropriate electroactive available surface and to avoid the surface passivation and sensor damage. This can be achieved by employing biocompatible nanofiber meshes that allow the cells to have a normal behavior and do not alter the electrochemical detection. For a better mechanical stability and ease of handling, nylon 6/6 nanofibers were collected on commercial polymeric membranes, at an optimal fiber density, obtaining a double-layered platform. To demonstrate the functionality of the fabricated scaffold, the screening of cellular stress has been achieved integrating melanoma B16-F10 cells and the (bio)sensor components on the transducer whereas the melanin exocytosis was successfully quantified using a commercial electrode. Either directly on the surface of the (bio)sensor or spatially detached from it, the integration of cell cultures in biosensing platforms based on electrospun nanofibers represents a powerful bioanalytical tool able to provide real-time information about the biomarker release, enzyme activity or inhibition, and monitoring of various cellular events.

A Gelatin-Based Biomimetic Scaffold Promoting Osteogenic Differentiation of Adipose-Derived Mesenchymal Stem Cells.

Background: In bone tissue engineering segment, numerous approaches have been investigated to address critically sized bone defects via 3D scaffolds, as the amount of autologous bone grafts are limited, accompanied with complications on harvesting. Moreover, the use of bone-marrow-derived stem cells is also a limiting factor owing to the invasive procedures involved and the low yield of stem cells. Hence, research is ongoing on the search for an ideal bone graft system promoting bone growth and regeneration. Purpose of the Study: This study aims to develop a unique platform for tissue development via stem cell differentiation towards an osteogenic phenotype providing optimum biological cues for cell adhesion, differentiation and proliferation using biomimetic gelatin-based scaffolds. The use of adipose-derived mesenchymal stem cells in this study also offers an ideal approach for the development of an autologous bone graft. Methods: A gelatin-vinyl acetate-based 3D scaffold system incorporating Bioglass was developed and the osteogenic differentiation of adipose-derived mesenchymal stem cells (ADMSCs) on the highly porous freeze-dried gelatin-vinyl acetate/ Bioglass scaffold (GB) system was analyzed. The physicochemical properties, cell proliferation and viability were investigated by seeding rat adipose tissue-derived mesenchymal stem cells (ADSCs) onto the scaffolds. The osteogenic differentiation potential of the ADMSC seeded GeVAc/bioglass system was assessed using calcium deposition assay and bone-related protein and genes and comparing with the 3D Gelatin vinyl acetate coppolymer (GeVAc) constructs. Results and Conclusion: According to the findings, the 3D porous GeVAc/bioglass scaffold can be considered as a promising matrix for bone tissue regeneration and the 3D architecture supports the differentiation of the ADMSCs into osteoblast cells and enhances the production of mineralized bone matrix.

Nanofibrous Microspheres: A Biomimetic Platform for Bone Tissue Regeneration.

Bone, a fundamental constituent of the human body, is a vital scaffold for support, protection, and locomotion, underscoring its pivotal role in maintaining skeletal integrity and overall functionality. However, factors such as trauma, disease, or aging can compromise bone structure, necessitating effective strategies for regeneration. Traditional approaches often lack biomimetic environments conducive to efficient tissue repair. Nanofibrous microspheres (NFMS) present a promising biomimetic platform for bone regeneration by mimicking the native extracellular matrix architecture. Through optimized fabrication techniques and the incorporation of active biomolecular components, NFMS can precisely replicate the nanostructure and biochemical cues essential for osteogenesis promotion. Furthermore, NFMS exhibit versatile properties, including tunable morphology, mechanical strength, and controlled release kinetics, augmenting their suitability for tailored bone tissue engineering applications. NFMS enhance cell recruitment, attachment, and proliferation, while promoting osteogenic differentiation and mineralization, thereby accelerating bone healing. This review highlights the pivotal role of NFMS in bone tissue engineering, elucidating their design principles and key attributes. By examining recent preclinical applications, we assess their current clinical status and discuss critical considerations for potential clinical translation. This review offers crucial insights for researchers at the intersection of biomaterials and tissue engineering, highlighting developments in this expanding field.

The effect of acellular scaffold loaded with Wharton's jelly-derived stem cells and mineral pitch on healing of burn model in rat.

Severe burns often result in an exacerbated inflammatory response, which can contribute to further injury. This inflammatory response may lead to an increased risk of infection, multiple organ failure, and death. This study aimed to investigate the potential of reducing inflammation to enhance burn wound healing in rats using ovine's small intestinal submucosa as a carrier for Wharton's jelly mesenchymal stem cells (WJ-MSCs) and Mineral Pitch (MP). A rat burn model was developed, and the animals were divided into four groups: control group: burn, placebo group: scaffold-treated burn, cell experimental group: WJ-MSCs seeded scaffold-treated burn, and cell and MP experimental group: scaffolds loaded with WJ-MSCs and MP-treated burn. After treating the wounds in the relevant groups and sampling them on days 5, 14 and 21, histological and pathological parameters, and the expression of genes involved in angiogenesis and epithelialization were evaluated. The study results revealed several findings in the burn wounds. These included changes in mast cell populations, a decrease in inflammatory neutrophils and lymphocytes, an increase in fibroblasts and blood vessels, and upregulation of angiogenesis and epithelialization genes. These changes collectively contributed to enhanced wound healing in cell and MP experimental group compared to the other groups. The findings suggest that scaffolds loaded with Wharton's jelly-derived stem cells and MP can serve as engineered tools to modulate inflammatory conditions during the burn wound healing process. These interventions can improve burn wound management and promote better outcomes.

Isolation and Visualization of Plant Stress Granule-Associated Components via On-Beads Digestion and Co-localization Analysis.

Stress granules (SGs) are conserved cytoplasmic biomolecular condensates mainly formed by proteins and RNA molecules assembled by liquid-liquid phase separation. Isolation of SGs components has been a major challenge in the field due to the dynamic and transient nature of stress granule shells. Here, we describe the methodology for the isolation and visualization of SGs proteins from Arabidopsis thaliana plants using a scaffold component as the target. The protocol consists of the first immunoprecipitation of GFP-tagged scaffold protein, followed by an on-beads enzymatic digestion and previous mass spectrometry identification. Finally, the localization of selected SGs candidates is visualized in Nicotiana benthamiana mesophyll protoplasts.

Applications of Graphene Family Nanomaterials in Regenerative Medicine: Recent Advances, Challenges, and Future Perspectives.

Graphene family nanomaterials (GFNs) have attracted considerable attention in diverse fields from engineering and electronics to biomedical applications because of their distinctive physicochemical properties such as large specific surface area, high mechanical strength, and favorable hydrophilic nature. Moreover, GFNs have demonstrated the ability to create an anti-inflammatory environment and exhibit antibacterial effects. Consequently, these materials hold immense potential in facilitating cell adhesion, proliferation, and differentiation, further promoting the repair and regeneration of various tissues, including bone, nerve, oral, myocardial, and vascular tissues. Note that challenges still persist in current applications, including concerns regarding biosecurity risks, inadequate adhesion performance, and unsuitable degradability as matrix materials. This review provides a comprehensive overview of current advancements in the utilization of GFNs in regenerative medicine, as well as their molecular mechanism and signaling targets in facilitating tissue repair and regeneration. Future research prospects for GFNs, such as potential in promoting ocular tissue regeneration, are also discussed in details. We hope to offer a valuable reference for the clinical application of GFNs in the treatment of bone defects, nerve damage, periodontitis, and atherosclerosis.

Antimicrobial poly (1,4-butylene carbonate): Preparation, characterization, and potential applications as a material for tympanic membrane repair.

Perforation of the tympanic membrane (TM) is a common condition that often requires a scaffold as a support for surgery. However, because of the external environment of the auditory canal, the scaffold could become bacterially infected and prevent the TM from healing. As a result, the perfect scaffold should have both antibacterial and biomimetic qualities. In this study, the biodegradable biomaterial poly(1,4-butylene carbonate) (PBC) films containing levofloxacin (LEV) was successfully prepared for the first time. The results showed that the hydrophilicity of the LEV/PBC film was improved after the addition of LEV, and the tensile strength was also complied with the requirements of the standard. The created antibacterial film demonstrated excellent antibacterial properties. In vitro hemolysis experiments revealed no risk of hemolysis for the new material, and the cytotoxicity study further confirmed its non-cytotoxic nature. Overall, LEV was a good component of PBC/LEV film, which is expected to be used for TM repair in the future.

Dual release of daptomycin and BMP-2 from a composite of ß-TCP ceramic and ADA gelatin.

BACKGROUND: Antibiotic-containing carrier systems are one option that offers the advantage of releasing active ingredients over a longer period of time. In vitro sustained drug release from a carrier system consisting of microporous ß-TCP ceramic and alginate has been reported in previous works. Alginate dialdehyde (ADA) gelatin gel showed both better mechanical properties when loaded into a ß-TCP ceramic and higher biodegradability than pure alginate. METHODS: Dual release of daptomycin and BMP-2 was measured on days 1, 2, 3, 6, 9, 14, 21, and 28 by HPLC and ELISA. After release, the microbial efficacy of the daptomycin was verified and the biocompatibility of the composite was tested in cell culture. RESULTS: Daptomycin and the model compound FITC protein A (n = 30) were released from the composite over 28 days. A Daptomycin release above the minimum inhibitory concentration (MIC) by day 9 and a burst release of 71.7 ± 5.9% were observed in the loaded ceramics. Low concentrations of BMP-2 were released from the loaded ceramics over 28 days.

Development of bilayer tissue-engineered scaffolds: combination of 3D printing and electrospinning methodologies.

Although different fabrication methods and biomaterials are used in scaffold development, hydrogels and electrospun materials that provide the closest environment to the extracellular matrix have recently attracted considerable interest in tissue engineering applications. However, some of the limitations encountered in the application of these methods alone in scaffold fabrication have increased the tendency to use these methods together. In this study, a bilayer scaffold was developed using 3D-printed gelatin methacryloyl (GelMA) hydrogel containing ciprofloxacin (CIP) and electrospun polycaprolactone (PCL)-collagen (COL) patches. The bilayer scaffolds were characterized in terms of chemical, morphological, mechanical, swelling, and degradation properties; drug release, antibacterial properties, and cytocompatibility of the scaffolds were also studied. In conclusion, bilayer GelMA-CIP/PCL-COL scaffolds, which exhibit sufficient porosity, mechanical strength, and antibacterial properties and also support cell growth, are promising potential substitutes in tissue engineering applications.

Investigating the indirect therapeutic effect of hAMSCs utilizing a novel scaffold (PGS-co-PCL/PGC/PPy/Gelatin) in myocardial ischemia-reperfusion-induced renal failure in male Wistar rats.

BACKGROUND: Myocardial ischemia-reperfusion (MI/R) occurs due to temporary or permanent interruptions in the coronary and circulatory system, indirectly affecting kidney function through reduced cardiac output for metabolic needs. In this study, the aim was to explore the indirect effects of using human amniotic membrane mesenchymal stem cells (hAMSCs) with the PGS-co-PCL/PGC/PPy/Gelatin scaffold in male rats with renal failure induced by miocardial ischemia-reperfusion. METHODS: MI/R injury was induced in 48 male Wistar rats through left anterior descending artery ligation, divided into four groups (n=12); control group, cell group, scaffold group, and celss+scaffold group. Evaluations were conducted at two and thirty days post MI/R injury, encompassing echocardiography, biochemical, inflammatory markers analysis, and histological assessment. RESULTS: Echocardiographic findings exhibited notable enhancement in ejection fraction, fractional shortening, and stroke volume of treated groups compared to controls after 30 days (P< 0.05). Serum creatinine (P< 0.001) and urea (P< 0.05) levels significantly decreased in the scaffold+cells group) compared to the control group. The treated cells+ scaffold group displayed improved kidney structure, evidenced by larger glomeruli and reduced Bowman's space compared to the control group (P< 0.01). Immunohistochemical analysis indicated reduced TNF-α protein in the scaffold+ cells group (P< 0.05) in contrast to the control group (P< 0.05). Inflammatory factors IL-6, TNF-α, and AKT gene expression in renal tissues were improved in scaffold+ cells-treated animals. CONCLUSION: Our research proposes the combination of hAMSCs and the PGS-co-PCL/PGC/PPy/Gelatin scaffold in MI/R injured rats appears to enhance renal function and reduce kidney inflammation by improving cardiac output.

Advancements in tissue engineering for cardiovascular health: a biomedical engineering perspective.

Myocardial infarction (MI) stands as a prominent contributor to global cardiovascular disease (CVD) mortality rates. Acute MI (AMI) can result in the loss of a large number of cardiomyocytes (CMs), which the adult heart struggles to replenish due to its limited regenerative capacity. Consequently, this deficit in CMs often precipitates severe complications such as heart failure (HF), with whole heart transplantation remaining the sole definitive treatment option, albeit constrained by inherent limitations. In response to these challenges, the integration of bio-functional materials within cardiac tissue engineering has emerged as a groundbreaking approach with significant potential for cardiac tissue replacement. Bioengineering strategies entail fortifying or substituting biological tissues through the orchestrated interplay of cells, engineering methodologies, and innovative materials. Biomaterial scaffolds, crucial in this paradigm, provide the essential microenvironment conducive to the assembly of functional cardiac tissue by encapsulating contracting cells. Indeed, the field of cardiac tissue engineering has witnessed remarkable strides, largely owing to the application of biomaterial scaffolds. However, inherent complexities persist, necessitating further exploration and innovation. This review delves into the pivotal role of biomaterial scaffolds in cardiac tissue engineering, shedding light on their utilization, challenges encountered, and promising avenues for future advancement. By critically examining the current landscape, we aim to catalyze progress toward more effective solutions for cardiac tissue regeneration and ultimately, improved outcomes for patients grappling with cardiovascular ailments.

A novel scaffold-free mesenchymal stem cell-derived tissue engineered construct for articular cartilage restoration - From basic to clinic.

Treatments for articular cartilage injuries are still challenging, due in part to its avascular and aneural surroundings. Since the first report of autologous chondrocyte implantation, cell-based therapies have been extensively studied with a variety of cell sources, including chondrocytes and mesenchymal stem/stromal cells (MSCs). Recently, MSC-based therapy has received considerable research attention because of the relative ease in handling for tissue harvest, and subsequent cell expansion and differentiation. Using such cells, we have originally developed a 3-dimensional scaffold-free tissue-engineered construct (TEC) through simple-cell culture methods and demonstrated its feasibility for cartilage repair and regeneration in the first-in-human clinical trial. This review summarizes our novel scaffold-free approaches to use MSC for the restoration of damaged articular cartilage, documenting the progression from basic to clinical studies.

Orthogonally woven 3D nanofiber scaffolds promote rapid soft tissue regeneration by enhancing bidirectional cell migration.

Repairing large-area soft tissue defects caused by traumas is a major surgical challenge. Developing multifunctional scaffolds with suitable scalability and favorable cellular response is crucial for soft tissue regeneration. In this study, we developed an orthogonally woven three-dimensional (3D) nanofiber scaffold combining electrospinning, weaving, and modified gas-foaming technology. The developed orthogonally woven 3D nanofiber scaffold had a modular design and controlled fiber alignment. In vitro, the orthogonally woven 3D nanofiber scaffold exhibited adjustable mechanical properties, good cell compatibility, and easy drug loading. In vivo, for one thing, the implantation of an orthogonally woven 3D nanofiber scaffold in a full abdominal wall defect model demonstrated that extensive granulation tissue formation with enough mechanical strength could promote recovery of abdominal wall defects while reducing intestinal adhesion. Another result of diabetic wound repair experiments suggested that orthogonally woven 3D nanofiber scaffolds had a higher wound healing ratio, granulation tissue formation, collagen deposition, and re-epithelialization. Taken together, this novel orthogonally woven 3D nanofiber scaffold may provide a promising and effective approach for optimal soft tissue regeneration.

Polymeric scaffold integrated with nanovesicle-entrapped curcuminoids for enhanced therapeutic efficacy.

Aim: Polymeric scaffolds were developed fortified with nanovesicle-encapsulated individual curcumin (CUR) and tetrahydrocurcumin (THC) for improved therapeutic efficacy due to their low stability and efficacy in native form. Method: Nanovesicle-encapsulated individual CUR and THC were fabricated using thin-film hydration techniques and characterized. Results & conclusion: CUR/THC in native and vesicle-encapsulated form demonstrated diminished LPS-instigate nitric oxide (NO) levels in macrophage cells in a concentration-dependent demeanor. However, vesicle-encapsulated CUR/THC inhibited NO production at lower concentrations, compared with the native CUR/THC form. Furthermore, the scaffold fortified with vesicle-encapsulated CUR/THC demonstrated improved physical properties with excellent antioxidant, biocompatibility, and human keratinocyte cell proliferation ability. The results recommended that nanovesicle-encapsulated THC can be retained as a potential substitute for CUR with improved therapeutic efficacy.

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Mesenchymal stem cell therapy using Pal-KTTKS-enriched carboxylated cellulose improves burn wound in rat model.

Despite the great progress in developing wound dressings, delayed wound closure still remains a global challenge. Thus, developing novel wound dressings and employing advanced strategies, including tissue engineering, are urgently desired. The carboxylated cellulose was developed through the in situ synthesis method and further reinforced by incorporating pal-KTTKS to stimulate collagen synthesis and improve wound healing. The developed composites supported cell adhesion and proliferation and showed good biocompatibility. To boost wound-healing performance, adipose-derived mesenchymal stem cells (MSC) were seeded on the pal-KTTKS-enriched composites to be implanted in a rat model of burn wound healing. Healthy male rats were randomly divided into four groups and wound-healing performance of Vaseline gauze (control), carboxylated cellulose (CBC), pal-KTTKS-enriched CBC (KTTKS-CBC), and MSCs seeded on the KTTKS-CBC composites (MSC-KTTKS-CBC) were evaluated on days 3, 7, and 14 post-implantation. In each group, the designed therapeutic dressings were renewed every 5 days to increase wound-healing performance. We found that KTTKS-CBC and MSC-KTTKS-CBC composites exhibited significantly better wound healing capability, as evidenced by significantly alleviated inflammation, increased collagen deposition, improved angiogenesis, and considerably accelerated wound closure. Nevertheless, the best wound-healing performance was observed in the MSC-KTTKS-CBC groups among all four groups. This research suggests that the MSC-KTTKS-CBC composite offers a great deal of promise as a wound dressing to enhance wound regeneration and expedite wound closure in the clinic.

In situ comparison of osteogenic effects of polymer-based scaffolds with different degradability by integrated scaffold model.

Polymer-based scaffolds with different degradability have been investigated to screen the matrix whose degradation rate is more closely matched with the bone regeneration rate. However, these comparisons are inclined to be compromised by the animal individual differences. In this study, we constructed an integrated scaffold model comprising four parts with different degradability and bioactivity to achieve an in situ comparison of bone regeneration ability of different scaffolds. Slow-degradable polycaprolactone (PCL), fast-degradable poly (lactic-co-glycolic acid) (PLGA), and silica-coated PCL and PLGA scaffolds were assembled into a round sheet to form a hydroxyapatite (HA)-free integrated scaffold. HA-doped PCL, PLGA, and silica-coated PCL and PLGA scaffolds were assembled to create an HA-incorporated integrated scaffold. The in vivo experimental results demonstrated that the local acid microenvironment caused by the rapid degradation of PLGA interfered with the osteogenic process promoted by PCL-based scaffolds in defect areas implanted with HA-free integrated scaffolds. Since the incorporation of HA alleviated the acidic microenvironment to some extent, each scaffold in HA-incorporated scaffolds exhibited its expected bone regeneration capacity. Consequently, it is feasible to construct an integrated structure for comparing the osteogenic effects of various scaffolds in situ, when there is no mutual interference between the materials. The strategy presented in this study inspired the structure design of biomaterials to enable in situ comparison of bone regeneration capacity of scaffolds.