Preliminary report of de novo adipogenesis using novel bioabsorbable implants and image evaluation using a porcine model.

Our bioabsorbable poly-L-lactic acid (PLLA) mesh implants containing collagen sponge are replaced with adipose tissue after implantation, and this is an innovative method for breast reconstruction. In this preliminary study, we investigated the formation of adipose tissue and evaluated the process via multimodal images in a porcine model using an implant aggregate to generate the larger adipose tissue. The implant aggregate consists of PLLA mesh implants containing collagen sponge and a poly-glycolic acid woven bag covering them. We inserted the implant aggregates under the porcine mammary glands. Magnetic resonance imaging (MRI), ultrasonography (USG), and 3-dimensional (3D) surface imaging and histological evaluations were performed to evaluate the formation of adipose tissue over time. The volume of the implant aggregate and the formed adipose tissue inside the implant aggregate could be evaluated over time via MRI. The space within the implant aggregate was not confirmed on USG due to the acoustic shadow of the PLLA threads. The change in volume was not confirmed precisely using 3D surface imaging. Histologically, the newly formed adipose tissue was confirmed on the skin side of the implant aggregate. This implant aggregate has the ability to regenerate adipose tissue, and MRI is an appropriate method for the evaluation of the volume of the implant aggregation and the formation of adipose tissue.

Efficacy of the dual controlled release of HGF and bFGF impregnated with a collagen/gelatin scaffold.

BACKGROUND: We previously developed collagen/gelatin sponges (CGS) able to sustain and release basic fibroblast growth factor (bFGF) and reported that this CGS impregnated with bFGF promoted dermis-like tissue formation. We herein confirmed the single-sustained release of hepatocyte growth factor (HGF) and the dual sustained release of HGF and bFGF from CGSs, and explored its efficacy using a murine model of skin defects. MATERIALS AND METHODS: The sustained release of HGF alone and both HGF and bFGF from CGSs were evaluated in vitro. CGSs (8 mm in diameter) impregnated with normal saline solution (NSS) (NSS group), HGF solution (10 or 50 µg/cm2) (HGF-L or HGF-H group), bFGF solution (7 µg/cm2) (bFGF group), or HGF (10 µg/cm2) and bFGF (7 µg/cm2) solution (HGF + bFGF group) were implanted into full-thickness skin defects on the backs of mice. The wound area, neoepithelium length, dermis-like tissue formation and newly formed capillaries were evaluated. RESULTS: The single release of HGF and the dual release of HGF and bFGF from CGSs were confirmed. At week 1, the wound closure and neoepithelium length were promoted in the HGF-L group compared with the NSS group. At week 2, the wound closure, neoepithelium length, dermis-like tissue formation and newly formed capillary formation were promoted in the bFGF and HGF + bFGF groups compared with the NSS and HGF-H groups. Newly formed capillary formation was superior in the HGF + bFGF group compared with the bFGF group. CONCLUSIONS: The dual release of HGF and bFGF from CGS was a promising treatment for full-thickness skin defects.

Cultured Human Epidermis Combined With Meshed Skin Autografts Accelerates Epithelialization and Granulation Tissue Formation in a Rat Model.

INTRODUCTION: As the take rate of cultured epidermal autografts in burn wound treatment is variable, widely expanded meshed auto skin grafts are often used in combination with cultured epidermal autograft to increase the take rate and achieve definitive wound coverage. However, a long time (3-4 weeks) required to prepare a cultured epidermis sheet is a disadvantage. Allogeneic cultured epidermis can be prepared in advance and cryopreserved to be used in combination with auto meshed skin grafts for treating third-degree burns. Nevertheless, the human cultured epidermis (hCE) has not been proved to accelerate wound healing after meshed skin grafting. Here, we investigated the effect of hCE on wound healing in a rat model of meshed skin grafting. MATERIALS AND METHODS: Human cultured epidermis was prepared from human neonatal foreskin and assessed by the release of growth factors into the culture medium using enzyme-linked immunosorbent assay. Skin wounds were inflicted on male F344 rats and treated by the application of widely meshed (6:1 ratio) autogenous skin grafts with or without hCE (n = 8 rats per group). Wound area, neoepithelium length, granulation tissue formation, and neovascularization were evaluated on day 7 postgrafting. RESULTS: Human cultured epidermis secreted IL-1α, Basic fibroblast growth factor, platelet-derived growth factor-AA, TGF-α, TGF-ß1, and vascular endothelial growth factor in vitro. In rats, hCE accelerated wound closure (P = 0.003), neoepithelium growth (P = 0.019), and granulation tissue formation (P = 0.043), and increased the number of capillaries (P = 0.0003) and gross neovascularization area (P = 0.008) compared with the control group. CONCLUSIONS: The application of hCE with meshed grafts promoted wound closure, possibly via secretion of growth factors critical for cell proliferation and migration, suggesting that hCE can enhance the healing effect of widely expanded skin autografts.

Efficacy of gelatin gel sheets in sustaining the release of basic fibroblast growth factor for murine skin defects.

BACKGROUND: Gelatin has been used as a material sustaining the release of basic fibroblast growth factor (bFGF), which promotes fibroblast proliferation and capillary formation and accelerates wound healing. In the application of these materials, bFGF is impregnated immediately before application, and it is difficult to conform the shape to the wound. In this study, we prepared a pliable and plastic gelatin gel sheet (GGS) that sustains bFGF and conforms to the shape of the wound as a result of cross-linking just before application. In addition, we examined the sustained release profile of bFGF from GGS and its effect on wound healing in murine skin defects. MATERIALS AND METHODS: A 13-wt% gelatin solution was mixed with bFGF before cross-linking with 1% glutaraldehyde solution. GGSs impregnated with 7 µg/cm(2) of bFGF were incubated in phosphate-buffered saline and collagenase solution, and GGS degradation and bFGF release were evaluated. In the murine experiments, GGSs treated without bFGF and GGSs impregnated with 1, 3.5, 7, or 14 µg/cm(2) of bFGF were applied to full-thickness skin defects created on the backs of C57BL/6JJcl mice, and the wound closure, epithelial length, extent of granulation tissue and capillary formation were compared. RESULTS: bFGF was released according to the degradation of GGS in phosphate-buffered saline, and the remaining bFGF was released in collagenase solution. In the animal studies, epithelialization was accelerated in the GGSs treated with 1 and 3.5 µg/cm(2) of bFGF, and granulation tissue formation and angiogenesis were promoted based on the amount of bFGF impregnated into the GGS. CONCLUSIONS: GGS impregnated with bFGF is capable of sustaining the release of bFGF, with consequent accelerated epithelialization, granulation tissue formation, and angiogenesis in vivo. GGS is a novel and promising wound dressing that sustains bFGF and can be adapted to the shape of various wounds in the treatment of both acute and chronic wounds.

Efficacy of gelatin gel sheets sustaining epidermal growth factor for murine skin defects.

BACKGROUND: Epidermal growth factor (EGF) plays an important role in wound healing. However, EGF must be applied daily due to rapid inactivation in vivo. We investigated the sustained release of EGF from gelatin gel sheets (GGSs) and the efficacy of GGSs impregnated with EGF for promoting wound healing. MATERIALS AND METHODS: GGSs impregnated with EGF were prepared by cross-linking via glutaraldehyde to gelatin solution containing EGF. The sustained release of EGF and the bioactivity of released EGF were evaluated. Then, three kinds of GGSs containing NSS (normal saline solution; NSS group), 2.5 µg of EGF (EGF-L group), or 25 µg of EGF (EGF-H group) were applied to full-thickness skin defects created on the backs of mice. The wounds covered with polyurethane film without GGS were used as a control (PUF group). The wound area, neoepithelium length, regenerated granulation tissue, and newly formed capillaries were evaluated. RESULTS: EGF was sustained and released from GGS as it degraded. The bioactivity of released EGF was confirmed. EGF-L group promoted the neoepithelium length, regenerated granulation tissue, and newly formed capillaries compared with those in the PUF and NSS groups. The area of regenerated granulation tissue in the NSS group (week 1: 2.6 + 0.2 mm(2), week 2: 2.8 + 0.3 mm(2)) was larger than that in the PUF group (week 1: 0.6 + 0.1 mm(2), week 2: 1.0 + 0.1 mm(2)). The area of newly formed capillaries in the EGF-L group (9967 + 1903 µm(2)) was larger than that of the EGF-H group (3485 + 1050 µm(2)). CONCLUSIONS: GGSs impregnated with EGF-L showed promising results regarding wound healing.

Exploration of the wound healing effect of topical administration of nicotine in combination with collagen scaffold in a rabbit model.

Nicotine has been reported to prolong the wound healing; however, we showed that the topical application of 10(-4) M nicotine promoted murine wound healing. The objective of this study was to explore the wound healing effects of nicotine in combination with collagen scaffold using skin defects in rabbit. Three full-thickness skin defects 8 mm in diameter were made on the rabbit auricle. Artificial dermis was applied to the defects, and 10 µl of nicotine solution (10(-5), 10(-4), and10(-3) M), bFGF solution (0.5 µg/10 µl), and both bFGF and 10(-4) M nicotine solutions were injected into the artificial dermis once daily for 7 days. Rabbits were sacrificed on day 10, 15, or 20, and the wound healing process was evaluated. bFGF was superior in the formation of the dermis-like tissue and capillaries. In nicotine groups, the epithelial length and the dermis-like tissue formations in the 10(-4) M group were superior, in contrast, those were inhibited in the 10(-3) M group. The synergistic effect of bFGF and 10(-4) M nicotine was not confirmed. This study suggests that the topical application of 10(-4) M nicotine promoted wound healing in rabbit, but the effect was not apparent compared with murine models.

Preparation of Partial-Thickness Burn Wounds in Rodents Using a New Experimental Burning Device.

OBJECTIVE: The manual application of hot water or hot metal to an animal's skin surface is often used to prepare burn wound models. However, manual burn creation is subject to human variability. We developed a new device that can control the temperature, time, and pressure of contact to produce precise and reproducible animal burn wounds and investigated the conditions required to prepare various burn wounds using our new device. METHODS: We prepared burn wounds on F344 rats using 3 contact times 2, 4, and 10 seconds using a stamp heated to 80°C. We observed the wound-healing process macroscopically and histologically and evaluated the burn depth using a laser speckle contrast-imaging device, which evaluated the blood flow of the wound. RESULTS: The changes in the burned area over time, tissue perfusion of the burn wounds, histological evaluation of the burn depth by hematoxylin-eosin and azocarmine and aniline blue staining, and the epithelialization rate (the ratio of the epithelialized area to the wound length) were evaluated on histological sections. Results indicated that the burn wounds prepared with contact times of 2, 4, and 10 seconds corresponded to superficial dermal burns, deep dermal burns, and full-thickness burns, respectively. CONCLUSIONS: We demonstrated that partial- and full-thickness burn wounds can be precisely and reproducibly created with our new automated burning device.

Rhinoplasty for post-traumatic deviation of the nose with non-incisional external perforated osteotomy.

Osteotomy is often necessary for the repair of post-traumatic nasal bone deformities. Typically, tools such as chisels are used for osteotomies; however, we performed osteotomies using Kirschner wires without making a skin incision. Between April 2011 and July 2022, we performed rhinoplasty with external perforated osteotomy using Kirschner wires in 13 patients with post-traumatic nasal bone deformities (9 males and 4 females; mean age, 34 years, range 12-51 years), all of whom exhibited improvement, with only one case showing mild residual cosmetic deformity. None of the patients requested further revision, and all were satisfied with their functional results. The non-incisional external perforated technique is a reasonable method that allows for bone osteotomies along the fracture line and is well-controlled, predictable, and reproducible.

Evaluation of adipogenesis over time using a novel bioabsorbable implant without the addition of exogenous cells or growth factors.

Background: Breast reconstruction is crucial for patients who have undergone mastectomy for breast cancer. Our bioabsorbable implants comprising an outer poly-l-lactic acid mesh and an inner component filled with collagen sponge promote and retain adipogenesis in vivo without the addition of exogenous cells or growth factors. In this study, we evaluated adipogenesis over time histologically and at the gene expression level using this implant in a rodent model. Methods: The implants were inserted in the inguinal and dorsal regions of the animals. At 1, 3, 6, and 12 months post-operation, the weight, volume, and histological assessment of all newly formed tissue were performed. We analyzed the formation of new adipose tissue using multiphoton microscopy and RNA sequencing. Results: Both in the inguinal and dorsal regions, adipose tissue began to form 1 month post-operation in the peripheral area. Angiogenesis into implants was observed until 3 months. At 6 months, microvessels matured and the amount of newly generated adipose tissue peaked and was uniformly distributed inside implants. The amount of newly generated adipose tissue decreased from 6 to 12 months but at 12 months, adipose tissue was equivalent to the native tissue histologically and in terms of gene expression. Conclusions: Our bioabsorbable implants could induce normal adipogenesis into the implants after subcutaneous implantation. Our implants can serve as a novel and safe material for breast reconstruction without requiring exogenous cells or growth factors.

A Case of Super-giant Basal Cell Carcinoma Initially Diagnosed as Multiple Traumas.

Basal cell carcinoma (BCC), which is relatively easy to diagnose in a clinical setting, is the most common malignant tumor in the skin. Conversely, a giant BCC, a tumor beyond 5 cm in diameter, is a rare disease. In particular, a giant BCC beyond 20 cm in diameter is called a super-giant BCC, which frequently invades into deeper tissues, including the dermis, bones, or muscles. Here, we present a case of a 71-year-old patient who was initially diagnosed with multiple traumas with a large periosteal defect of the head. The ulcer was surrounded by malodorous necrotic tissue and slough, and several bacteria that caused necrotizing fasciitis were detected. Mapping biopsies after extensive debridement yielded BCC, and therefore, he was finally diagnosed with a super-giant BCC. A careful consultation revealed a history of ulcer on the head after a head injury approximately 10 years ago. He underwent radical dissection including the external table of the skull, followed by a free latissimus dorsi muscle flap with a meshed split-thickness skin graft. Because of the slow and chronic development of a super-giant BCC, accurate diagnosis is often difficult. Careful attention should be paid in patients with long-sustained ulcers.

Development of new bioabsorbable implants with de novo adipogenesis.

Poly-L-lactic acid (PLLA) mesh implants containing collagen sponge (CS) were replaced with autologous adipose tissue regeneration in vivo. Herein, we investigated the optimal external frames and internal fillings using poly (lactic-co-ε-caprolactone) (P (LA/CL)), PLLA, and low-molecular-weight PLLA (LMW-PLLA) as the external frame and polyglycolic acid (PGA) nanosheets and CS as the internal filling. We prepared six implants: P (LA/CL) with PGA nano, PLLA with PGA nano, PLLA with CS, PLLA with 1/2 CS, PLLA with 1/4 CS, and LMW-PLLA with CS, and evaluated adipogenesis at 6 and 12 months using a rat inguinal model. The internal spaces in the P (LA/CL) and LMW-PLLA implants collapsed at 6 months, whereas those in the other four implants collapsed at 12 months. Adipose tissue regeneration was not significantly different between the PLLA-implanted groups at 6 and 12 months and was greater than that in the P (LA/CL) with PGA nano and LMW-PLLA with CS groups. The PGA nanosheet inside PLLA was comparable to the CS inside PLLA in the regeneration of adipose tissue and macrophage infiltration. In summary, PLLA is a promising external frame material in which the internal space can be replaced with adipose tissue. Thus, PGA nanosheets are an alternative internal filling material for adipose tissue regeneration.

Long term observation of de novo adipogenesis using novel bioabsorbable implants with larger size in a porcine model.

Introduction: The regeneration of adipose tissue in patients after breast cancer surgery would be desirable without the use of growth factors or cells to avoid potential recurrence and metastasis. We reported that prolate spheroidal-shaped poly-L-lactic acid (PLLA) mesh implants of approximately 18-mm polar diameter and 7.5-mm greatest equatorial diameter containing collagen sponge (CS) would be replaced by regenerated adipose tissue after implantation, thereby suggesting an innovative method for breast reconstruction. Our study aimed to evaluate the adipose tissue regeneration ability of implant aggregates in a porcine model. Methods: We prepared implant aggregates consisting of thirty PLLA mesh implants containing CS packed in a woven poly (glycolic acid) bag. The implant aggregates were inserted under the mammary glands in the porcine abdomen for a year. Single and double groups were classified by inserting either one or two implant aggregates on each side of the abdomen, respectively. Results: In both groups, the volume of the implant aggregates decreased over time, and the formation of adipose tissue peaked between 6 and 9 months. Histologically, the formation of adipose tissue was confirmed in the area that was in contact with native adipose tissue. Conclusions: Our implant aggregates could induce the autologous adipose tissue after long term implantation in vivo, without the use of any growth factor or cell treatment, presenting a potential novel method of breast reconstruction.

Inactivated Nevus Tissue with High Hydrostatic Pressure Treatment Used as a Dermal Substitute after a 28-Day Cryopreservation Period.

BACKGROUND: Giant congenital melanocytic nevi (GCMN) treatment remains controversial. While surgical resection is the best option for complete removal, skin shortage to reconstruct the skin defect remains an issue. We report a novel treatment using a high hydrostatic pressurization (HHP) technique and a cryopreservation procedure. However, cryopreservation may inhibit revascularization of implanted nevus tissue and cultured epidermal autograft (CEA) take. We aimed to investigate the influence of the cryopreservation procedure on the HHP-treated dermis specimen and CEA take on cryopreserved tissue. METHODS: Nevus tissue harvested from a patient with GCMN was inactivated with HHP of 200 MPa and then cryopreserved at -30°C for 28 days. The cryopreserved specimen was compared with fresh (HHP-treated without cryopreservation) tissue and with untreated (without HHP treatment) tissue to evaluate the extracellular matrix, basal membranes, and capillaries. Cultured epidermis (CE) take on the cryopreserved tissue was evaluated following implantation of the cryopreserved nevus tissue with CE into the subcutis of nude mice. RESULTS: No difference was observed between cryopreserved and fresh tissue in terms of collagen or elastic fibers, dermal capillaries, or basement membranes at the epidermal-dermal junction. In 4 of 6 samples (67%), applied CE took on the nevus tissues and regenerated the epidermis in the cryopreserved group compared with 5 of 6 samples (83%) in the fresh group. CONCLUSION: Cryopreservation at -30°C for 28 days did not result in significant damage to inactivated nevus tissue, and applied CE on the cryopreserved nevus tissues took and regenerated the epidermis. Inactivated nevus tissue with HHP can be used as a dermal substitute after 28-day cryopreservation.

Cultured epithelial autografts for the treatment of large-to-giant congenital melanocytic nevus in 31 patients.

INTRODUCTION: Giant congenital melanocytic nevus (GCMN) is a large melanocytic nevus, and its full-thickness removal is usually difficult due to the lack of skin available for reconstruction. Curettage is an alternative approach in cases of GCMN to remove the superficial dermis above the cleavage plane with a curette in the neonatal period, and its major complications include repigmentation, retarded epithelization, and hypertrophic scar formation. In Japan, the JACE® cultured epidermal autograft (CEA) was approved and covered by public healthcare insurance for the treatment of congenital melanocytic nevus (CMN) that is difficult to treat with conventional methods in 2016. We have used CEA for wounds after curettage in the neonatal period or following ablation after the neonatal period in combination with laser therapies to reduce the above-mentioned complications. METHODS: In this study, we summarized all consecutive CMN patients treated using CEA from December 2016 to April 2019 and evaluated the duration required for epithelialization, incidence of hypertrophic scar, and color change in the target nevus by comparing the L∗ values one year later between the Curettage group, the non-Curettage group with initial treatment or the subsequent group. RESULTS: No significant differences were seen in the epithelization period or incidence of hypertrophic scars among the groups, but the color of the target nevus was improved significantly in the Curettage group (p < 0.01) and non-Curettage group with initial treatment (p < 0.01). CONCLUSIONS: In conclusion, CEA seems to accelerate epithelization after curettage or ablation of CMN, and this treatment could improve the color of CMN when applied initially.

Ex vivo Induction of Apoptotic Mesenchymal Stem Cell by High Hydrostatic Pressure.

Among promising solutions for tissue repair and wound healing, mesenchymal stem (or stromal) cells (MSCs) have been a focus of attention and have become the most clinically studied experimental cell therapy. Recent studies reported the importance of apoptosis in MSC-mediated immunomodulation, in which apoptotic MSCs (apoMSCs) were shown to be superior to living MSCs. Nowadays, high hydrostatic pressure (HHP), a physical technique that uses only fluid pressure, has been developed and applied in various bioscience fields, including biotechnology, biomaterials, and regenerative medicine, as its safe and simply operation. In the current study, we investigated the impact of HHP treatment on human bone marrow-MSC survival and proliferation. Based on the detection of executioner caspase activation, phosphatidylserine exposure, DNA fragmentation (TUNEL) and irrefutable ultrastructural morphological changes on transmission electron microscopy (TEM), our data revealed that HHP treatment induced complete apoptosis in MSCs. Notably, this technique might provide manipulated products for use in cell-based therapies as manufacturing capability expands. We hope that our findings will contribute to the improvement of MSCs or EVs in translational research development. Graphical Abstract.

Bilateral plantar fibromatosis complicated by Dupuytren's contracture.

Plantar fibromatosis (PF) is a rare benign disease. Here we report bilateral PF accompanied by Dupuytren's contracture in the right palm. Magnetic resonance imaging was useful in diagnosing PF, although biopsy was needed to rule out hemangioma. As the patient had been receiving female hormone therapy since orchiectomy, there may be a possibility that estrogen accelerated the growth of PF. Local excision with a 1-cm margin was performed, followed by primary wound closure. Neither complication nor recurrence had occurred 6 months after the surgery.

Adipose tissue regeneration in a 3D-printed poly(lactic acid) frame-supported space in the inguinal region of rats.

BACKGROUND: Adipose tissue engineering has been studied as an alternative to current options for breast reconstruction, such as lipofilling, flap reconstruction, and silicone implants. Previously, we demonstrated that a poly(L-lactic acid) mesh containing a collagen sponge, containing neither cells nor growth factors, could be filled with the regenerated adipose tissues when implanted in rodent models. However, the main factor contributing to adipogenesis remained unclear. OBJECTIVE: We aimed to clarify whether adipogenesis can be achieved by the space provided by the mesh or by the bioactivity of collagen. METHODS: A three-dimensional (3D) poly(lactic acid) (PLA) frame, which was stiff enough to maintain its shape, was fabricated by 3D printing. The frame with (PLA+ColI) or without (PLA only) a type I collagen hydrogel was implanted in the inguinal region of rats for up to 12 months. Adipose tissue regeneration in the PLA only and PLA+ColI groups was evaluated histologically. RESULTS: The 3D PLA frame maintained its structure for 12 months in vivo and oil red O (ORO)-positive adipose tissues were regenerated in the frame. No significant difference in the ORO-positive area was detected between the PLA only and PLA+ColI groups. CONCLUSION: The space supported by the frame was a key factor in adipogenesis in vivo.

Human cultured epidermis accelerates wound healing regardless of its viability in a diabetic mouse model.

Allogeneic cultured epidermis (allo-CE) is a cultured keratinocyte sheet manufactured from donor cells and promotes wound healing when used in deep dermal burns, donor sites, and chronic ulcers and serves as a wound dressing. Allo-CE is usually cryopreserved to be ready to use. However, the cryopreservation procedure will damage the cell viability, and the influence of Allo-CE, according to its viability or wound healing process, has not been evaluated sufficiently. In this study, we aimed to prove the influence of keratinocyte viability contained in allo-CEs on wound healing. We prepared CEs with Green's method using keratinocytes obtained from a polydactyly patient and then prepared four kinds of CEs with different cell viabilities [fresh, cryopreserved, frozen, and FT (freeze and thaw)]. The cell viabilities of fresh, cryopreserved, frozen, and FT CEs were 95.7%, 59.9%, 16.7%, and 0.0%, respectively. The four CEs had homogeneous characteristics, except for small gaps found in the FT sheet by transmission electron microscopy observation. The four CEs were applied on the full-thickness skin defect of diabetic mice (BKS.Cg-Dock 7m +/+ Leprdb/Jcl), and the wound area and neoepithelium length were evaluated on days 4, 7, and 14. As a result, FT CEs without viable cells similarly promoted epithelialization on days 4 and 7 (p<0.05) and accelerated wound closure on day 7 (p<0.01) as fresh CEs compared with the control group. In conclusion, the promoting effect of allo-CE on wound healing does not depend on cell viability. Lyophilized CEs may be a suitable wound dressing with a long storage period at room temperature.

De novo adipogenesis using a bioabsorbable implant without additional cells or growth factors.

Adipose tissue regeneration in breast cancer patients without additional growth factors or adipose-tissue-derived stromal cells is desirable because of the possibility of recurrence and metastasis. We report that a poly-L-lactic acid (PLLA) mesh implant containing a collagen sponge (CS) maintained the internal space in vivo for up to 12 months and substituted for adipose tissue. We developed a PLLA capsule that maintained the internal space longer than that of PLLA mesh and compared adipose tissue formation at 12 and 24 months after implantation between the PLLA mesh with CS implant and the PLLA capsule implant with or without CS in a rabbit model. After 12 months, all implants maintained the internal space, and the adipose tissue that formed in all implant groups was larger than that in the control group. At 24 months, PLLA mesh maintained the internal space just as well as that at 12 months, while the PLLA capsule collapsed and accumulated a large number of macrophages. The formed adipose tissue in the PLLA mesh group was maintained up to 24 months; however, those in two PLLA capsule groups decreased and showed no difference from the control group. In conclusion, the internal space of the PLLA mesh implant with CS was substituted for adipose tissue at 12 months and sustained the formed adipose tissue after 24 months. The PLLA mesh implant containing CS is a desirable bioabsorbable implant that can be replaced by autologous adipose tissue after implantation in vivo without using any growth factors or cells.