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PubMed2026

Repair and regeneration across the lifespan: an ontogenetic perspective.

The capacity for tissue repair and regeneration undergoes a profound and progressive decline across the human lifespan, representing a fundamental driver of aging and chronic disease. This review establishes a comprehensive ontogenetic framework by mapping the continuous biological transition from the flawless, scarless regenerative plasticity of embryonic development to the irreversible fibrotic scarring and organ failure characteristic of senescence. We synthesize the hierarchical collapse of reparative networks across multiple biological scales. Importantly, this ontogenetic decline should not be interpreted as a purely degenerative trajectory but rather as a dynamic systems-level reprogramming in which evolutionary trade-offs prioritize tumor suppression, immune surveillance, and reproductive fitness over long-term regenerative fidelity. Recognizing this adaptive reallocation of biological resources reframes aging not simply as failure but as a predictable recalibration of repair hierarchies. At the molecular and cellular levels, the accumulation of genomic instability, unresolvable DNA damage, and mitochondrial dysfunction gradually overwhelms intracellular quality-control mechanisms. Concurrently, epigenetic drift and chronic, low-grade systemic inflammation ("inflammaging") dismantle the stem cell niche, driving adult stem cell exhaustion and shifting wound healing away from functional tissue replacement toward maladaptive fibrosis. Furthermore, we examine divergent, organ-specific repair trajectories. By contrasting the severe regenerative restrictions of the adult central nervous system and myocardium with the persistent, yet exhaustible, resilience of the liver, we elucidate the unique intrinsic and microenvironmental barriers that impede structural and functional recovery. Finally, we evaluate the clinical paradigm shift from passive management of age-related degeneration to active restoration of tissue integrity. By integrating systemic geroscience-which addresses the global hallmarks of aging-with targeted bioengineering and in vivo epigenetic modulation, contemporary regenerative medicine seeks to recreate permissive, youthful microenvironments. Ultimately, mastering these ontogenetic principles holds unprecedented potential to reactivate endogenous repair pathways, mitigate multi-organ collapse, and significantly extend human functional healthspan.

DNA repair↗
PubMed2026

Beyond Earth: Recent Advancements in Microgravity Biomedical and Genetic Research in Saudi Arabia.

Microgravity research has emerged as a rapidly evolving field at the intersection of space medicine, genomics, biotechnology, and precision medicine. Exposure to the space environment induces complex physiological and molecular adaptations that affect multiple biological systems, including immune regulation, metabolism, musculoskeletal function, and gene expression. Recent advances in genomics, multi-omics technologies, artificial intelligence, and bioengineering have substantially improved our understanding of biological adaptation to spaceflight and expanded opportunities for translational biomedical research. This review summarizes recent advances in genetic and biomedical research under microgravity conditions, with particular emphasis on molecular mechanisms, omics technologies, genome editing, microbiome research, regenerative medicine, and personalized healthcare approaches. Major experimental platforms, landmark spaceflight studies, and translational applications in infectious diseases, cancer biology, aging, tissue engineering, and pharmaceutical development are discussed. The review also highlights Saudi Arabia's emerging contributions to genomic medicine and space biosciences through initiatives such as the Saudi Human Genome Program, the Saudi Pangenome Project, the Saudi Space Agency, and the BioGravity Initiative. Recent Saudi participation in human spaceflight and microgravity-associated biomedical research is discussed within the context of Vision 2030 and national investments in biotechnology and precision medicine. Collectively, advances in microgravity research are expected to contribute to the advancement of precision medicine and facilitate the development of innovative diagnostic and therapeutic strategies with significant implications for both human space exploration and terrestrial healthcare.

Humans↗
PubMed2006

End-stage organ failure: will regenerative medicine keep its promise?

End-stage organ failure is a major cause of death worldwide that can occur in patients of all ages and transplantation is the current standard of care for chronic end-stage disease of many organs. Despite the success of organ transplantation, it is becoming clear that there will never be enough organs made available through donation to meet the increasing demand. The past decade's rapid advancement in stem cell biology and tissue engineering generated an explosive outburst of reports that gave rise to regenerative medicine, a new field that promises to "fix" damaged organs through regeneration provided by transplanted cells, stimulation of endogenous repair mechanisms, or implantation of bioengineered tissue. Whether, and if so when, regenerative medicine will keep its promise is uncertain. As we continue to strive to find new effective solutions, alternative approaches based on the development of targeted, preventive interventions aimed at maintaining normal organ function, instead of repairing organ damage, should also be pursued.

History, 18th Century↗
PubMed1985

Modular prosthetic system for segmental bone and joint replacement after tumor resection.

The increased interest in limb saving resection for malignant bone tumors emphasizes the need for continued research and development to improve techniques of oncological reconstruction. The bioengineer plays an important role on the limb salvage team. At the present time, custom joint implants are opening up new horizons in rehabilitation of patients following resection of bone tumors. In the future, modular prosthetic systems such as the system described will eliminate the need for individual, customized manufacture of prostheses and will make these oncological reconstructive techniques more available.

Biomechanical Phenomena↗
PubMed2001

Cell kinetics in a model of artificial skin. An immunohistochemical and flow cytometric analysis.

Bioengineered organs raised in vitro are candidate substitutes for natural organs in biological, pharmacological and clinical applications. We have studied cell kinetics in a human skin equivalent (HSE) using a combined immunohistochemical and flow cytometric approach. Morphological analysis has shown that, relative to unstimulated natural skin, cell proliferation mainly occurs in the basal layer of the epidermal equivalent. Immunohistochemical and flow cytometric measurements of the growth fraction suggested a cell turnover comparable to that of natural skin. Immunohistochemical labelling indices matched well with flow cytometric data. These observations are consistent with morphological and histochemical data demonstrating normal cell differentiation and tissue architecture in HSE and suggest that such HSE may be a usefull substitute for human skin.

Biocompatible Materials↗
PubMed2026

mRNA therapy: A novel approach for retinal neurodegenerative diseases.

Retinal neurodegeneration remains a major cause of irreversible vision loss, yet current therapeutic options are limited in effectiveness. Although gene therapies have shown clinical potential, the overexpression platforms they rely on, such as adeno-associated virus DNA, are constrained by safety concerns, limited efficacy, and cargo size restrictions. In contrast, mRNA therapy has gained recognition as a compelling alternative, enabling rapid and efficient protein expression without the risk of genomic integration. This review synthesizes recent advances in mRNA engineering, delivery systems, and administration routes for retinal applications, and highlight strategies to enhance targeting, penetration, and controlled release through interdisciplinary collaboration between ophthalmology and bioengineering. In recent years, engineered mRNA formats, including chemically modified linear, circular, and self-amplifying RNA, can achieve higher translation efficiency within a tunable expression window. The transient nature and relatively low immunogenicity of in vitro transcribed mRNA support repeat dosing without insertional mutagenesis. Advances in nanocarriers, particularly lipid nanoparticles, have enabled preferential delivery to retinal neurons, Müller glia, and pigment epithelium via intraocular administration, while improving mRNA stability and transfection efficiency. In preclinical studies, mRNA has been widely used to deliver gene-editing tools, transcription factors, and supplementary functional proteins. In disease models such as optic nerve crush and laser-induced choroidal neovascularization, mRNA-based therapies enhance neuroprotection and suppress pathological angiogenesis in the injured retina, with favorable ocular safety profiles. However, it remains largely unexplored how the intrinsic advantages of mRNA therapy can be leveraged to develop tailored strategies for complex retinal disorders. Consistent with this gap, mRNA platforms have not yet been widely incorporated into retinal research or clinical practice. In parallel, clinical translation also lags: despite encouraging outcomes of lipid nanoparticle-mRNA formulations in preclinical models, no candidates have progressed into retinal clinical trials. This review draws on the complex pathology and therapeutic logic of retinal neurodegeneration. It proposes that mRNA therapy enables multitarget, repeatable, stage-specific interventions that align with the dynamic evolution of diseases and the requirements of combination therapy in retinal diseases. It may be used to support neuroprotection, axon regeneration, and neurovascular regulation. By integrating data across experimental models and modalities, this review outlines representative cases and experimental paradigms to guide rational trial design and carrier selection. Taken together, technical progress and evolving application strategies position mRNA therapy as a compelling therapeutic avenue for retinal neurodegeneration.

administration↗
PubMed2006

Matrix-bound growth factors in tissue repair.

Morphogenesis in tissue development and repair is guided by a variety of signals from the extracellular milieu, including growth factors that are sequestered in the extracellular matrix. Bioengineering approaches have been developed to mimic the natural interactions between growth factors and the extracellular matrix, by engineering biomolecules as novel growth factors and as novel matrix components.

Biocompatible Materials↗
PubMed1977

Gait rehabilitation for an arm amputee.

This report is concerned with a male motor bike rider who was injured in a collision with a semi-trailer in June 1974. As a result of his injuries he had his right arm amputated, his right knee restricted, and his right foot partially amputated and pinned. This article presents the subsequent management of the patient which was aimed at achieving an acceptable foot and preventing further breakdown in other body linkages. The design of appliances and treatment were carried out by the physiotherapist, the chiropodist, and the bioengineer.

Amputees↗
PubMed1991

[Immunotherapy and urological malignancy].

Immunotherapy gained popularity as a treatment modality for malignant diseases in the 1960s. A number of trials, using tumor vaccines, immunopotentiators, interferons, cytokines and others, demonstrated antitumor effects in several urological malignancies, and, to date, immunotherapy plays a major role in treatment of advanced renal cell carcinoma and superficial bladder carcinoma. Interferon or interleukin-2, which became available for large scale clinical trial with the development of bioengineering, however, were shown to be not effective as initially expected, by single agent. Rational design of new strategies with multiple agents in combination based on basic and clinical research, should provide progress in treatment of urological malignancies.

BCG Vaccine↗
PubMed1997

Novel methodology to obtain salient biomechanical characteristics of insole materials.

Viscoelastic inserts are commonly used as artificial shock absorbers to prevent neuropathic foot ulcerations by decreasing pressure on the sole of the foot. Unfortunately, there is little scientific information available to guide physicians in the selection of appropriate insole materials. Therefore, a novel methodology was developed to form a rational platform for biomechanical characterizations of insole material durability, which consisted of in vivo gait analysis and in vitro bioengineering measurements. Results show significant differences in the compressive stiffness of the tested insoles and the rate of change over time in both compressive stiffness and peak pressures measured. Good correlations were found between pressure-time integral and Young's modulus (r2 = 0.93), and total energy applied and Young's modulus (r2 = 0.87).

Biomechanical Phenomena↗
PubMed2000

The potential benefits of advanced therapeutic modalities in the treatment of diabetic foot wounds.

This article discusses the advantages and disadvantages of primary wound healing as compared with primary amputation in individuals with chronic diabetic foot wounds. The authors review the potential benefits of vascular surgical procedures and advanced dressings, including two of the most promising modalities in modern wound care: growth factors and bioengineered skin. In this era of cost-conscious health-care administration, it is incumbent on the practitioner to consider not only the basic science of wound care, but also the economic aspect of treatment rendered. These various interventions, dressings, growth factor delivery systems, and new modalities could significantly reduce healing time, thereby reducing the risk of infection, hospitalization, and amputation while improving quality of life. If so, they may be truly cost-effective.

Bandages↗
PubMed1999

Rheumatoid arthritis and primary care: the case for early diagnosis and treatment.

Rheumatoid arthritis is a chronic inflammatory disease that can cause severe pain and disability. Disease management historically was based on a "therapeutic pyramid" in which treatment escalated as symptoms worsened. However, the demonstration of early joint damage in patients with rheumatoid arthritis has emphasized the importance of early identification and treatment. Key features in establishing a diagnosis include joint examinations, assessments of extra-articular manifestations, laboratory tests, and radiologic examinations. Care must be taken to rule out other disorders with symptoms that overlap those of rheumatoid arthritis. Treatment of rheumatoid arthritis typically involves disease-modifying antirheumatic drugs, nonsteroidal anti-inflammatory drugs, and low-dose corticosteroids--often used in combination. A new class of therapeutic agents designed to neutralize inflammatory cytokines has added a new dimension to the therapeutic armamentarium against rheumatoid arthritis. Etanercept, a bioengineered soluble receptor fusion protein that blocks tumor necrosis factor activity, is the first compound in this class to be approved for treatment of patients with refractory rheumatoid arthritis. Therapeutic trials indicate that etanercept can reduce disease activity with relatively few drug-related adverse effects, thus helping persons with rheumatoid arthritis return to more normal, healthy lives.

Adult↗
PubMed1984

Occupational health in advanced countries in the next century.

The gift of prophecy is rare but an attempt is made to forecast some of the developments in occupational health in the next century. People will not change nor will the natural laws or the properties of chemicals. The biological environment may alter significantly as a result of bioengineering. Environmental stresses will be different but the psychosocial responses will remain the same. Many of the current problems of dose-response relationships will be resolved by time and experience, though inevitably new problems will arise. The level of expectation of health will continue to exceed the resources available.

Environmental Exposure↗
PubMed1999

Care of venous leg ulcers.

For many decades, few advances occurred in the treatment of venous ulcers. Clinicians mainly relied on compression using gauze impregnated with zinc oxide--the Unna boot. During the past few years, however, much has changed in favor of clinicians. A variety of compression bandages are now available along with effective wound dressings that take advantage of moist wound healing, better topical agents, new systemic therapies, and living bioengineered skin. In fact, the problem facing clinicians today may be in deciding what treatments to use in addition to compression therapy, which remains the accepted standard of care for venous ulcers. This paper discusses advances that have occurred during the past several years in the understanding and treatment of venous leg ulcers, and their implications for clinical practice, education, and future research.

Bandages↗
PubMed1997

The chasm: what can be done, and what should be done.

The case study of growth hormone in short-stature children offers an example of the high cost of bioengineered therapies and the attendant ethical concerns. Despite uncertainties as to its efficacy, it is estimated that the annual U.S. expenditure for growth hormone, which costs about $20,000 per year for a 30 kg child, exceeds $375 million dollars. Ultimately, at this point in its evolution, the use of GH therapy illustrates the dilemma commonly created by new medical technology--the chasm between what can be done and what should be done. Unfortunately, the knowledge of what can be done precedes the understanding of what should be done.

Child↗
PubMed1991

Dacron collateral ligament reconstruction with proximal interphalangeal joint arthroplasty.

A porous Dacron (Phoenix Bioengineering, Bridgeport, PA) tendon is described for collateral ligament reconstruction and augumentation with proximal interphalangeal joint implant arthroplasty. Eight cases with a minimum follow-up of 15 months are reviewed. Diagnoses include posttraumatic arthritis and osteoarthritis, as well as rheumatoid arthritis. The porous Dacron tendon is constructed as a collagen-like weave. It has been useful in patients who have insufficient local tissue to achieve lateral proximal interphalangeal joint stability. In selected cases, it can obviate the need for a tendon graft and provide an alternative to arthrodesis.

Adult↗
PubMed1999

Abrogation of the hematological and biological activities of the interleukin-3/granulocyte-macrophage colony-stimulating factor fusion protein PIXY321 by neutralizing anti-PIXY321 antibodies in cancer patients receiving high-dose carboplatin.

This dose-escalation study was performed to evaluate the hematologic activity, biological effects, immunogenicity, and toxicity of PIXY321 (an interleukin-3/granulocyte-macrophage colony-stimulating factor fusion protein) administered after high-dose carboplatin (CBDCA) treatment. Patients with advanced cancers received CBDCA at 800 mg/m2 intravenously on day 0 of repeated 28-day cycles. In part A of the study, patients were treated with CBDCA alone during cycle 1 and then received PIXY321 on days 1 through 18 of cycle 2 and later cycles. In part B, patients received 18 days of PIXY321 beginning on day 1 of all CBDCA cycles, including cycle 1. PIXY321 was administered subcutaneously in 2 divided doses. Total doses of 135, 250, 500, 750, and 1,000 micrograms/m2/d were administered to successive cohorts of 3 to 6 patients in part A. In part B, patient groups received PIXY321 doses of 750, 1,000, and 1,250 micrograms/m2/d. The hematologic effects of PIXY321 were assessed in the first 2 cycles of therapy. Anti-PIXY321 antibody formation was assessed by enzyme-linked immunosorbent assay (ELISA) and neutralization assay. Of the 49 patients enrolled, 31 were fully evaluable for hematologic efficacy. When comparing the first B cycle (cycle B-1; with PIXY321) with the first A cycle (cycle A-1; without PIXY321), the fusion protein had no significant effect on platelet nadirs or duration of platelets less than 20,000/microL but was able to speed the time of recovery of platelet counts to 100,000/microL (15 v 20 days; P =.01). Significant improvements in neutrophil nadir and duration of ANC less than 500 were observed in cycles A-2 and B-1 (with PIXY321) as compared with cycle A-1 (without PIXY321). Initial PIXY321 prophylaxis (cycle A-2 and cycle B-1), enhanced the recovery of ANC to greater than 1,500/microL by an average of at least 8 days as compared with cycle A-1 (without PIXY321; P </=.004). However, positive PIXY321 hematologic effects were lost in the second course of PIXY321 among patients treated in part B. ELISA analysis showed that 92% of patients had developed neutralizing anti-PIXY321 antibodies by the completion of 2 PIXY321-containing cycles. The incidental action of PIXY321 to depress serum cholesterol levels was also abrogated during cycle B-2. We conclude that PIXY321 was active in speeding hematologic recovery but that neutralizing anti-PIXY321 antibody formation suppressed the hematologic and biochemical effects by the second cycle of PIXY321 administration. The immunogenicity of this fusion protein provides a cautionary warning that clinical development of bioengineered human molecules requires thorough testing for immune neutralization.

Adult↗
PubMed1980

Major pressure of sores.

A survey of 999 patients within the Borders Health Board area showed that 9.4 per cent had at least one pressure sore. J.C. Barbenel, M.M. Jordan and S.M. Nicol of the bioengineering unit, University of Strathclyde, describe how they assessed the extent and distribution of the condition, estimated to cost the NHS pound 150m a year.

Adult↗